LymphomasPhase 1/2NCT01851369

TRC102 and Temozolomide for Relapsed Solid Tumors and Lymphomas

A Phase 1/2 study testing TRC102, CT scan and Lomotil in people with Lymphomas and Solid Tumors, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Background: Methoxyamine hydrochloride (TRC102) is a new cancer treatment drug that may help improve the results of chemotherapy. It blocks tumor cells' attempts to repair damaged deoxyribonucleic acid (DNA), which may allow chemotherapy to kill the cells more easily. Read more about this study

Who is it for?: Ages 18 to 120 years
Conditions the study is for: Lymphomas, Solid Tumors, NSCLC
What is being tested?: TRC102, CT scan and Lomotil
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 93 participants
Where: 1 siteUnited States
Study dates: 12 Jul 2013to 1 Aug 2023
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 120 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

None listed.

Who cannot join

Patients who are actively receiving any other investigational agents.
Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for greater than or equal to 4 weeks without requiring steroid and anti-seizure medications are eligible to participate.
Phase II only: No other prior malignancies are allowed except for the following:
Adequately managed stage 0 (carcinoma in situ), I, or II basal cell or squamous cell carcinoma from which the patient is currently in complete remission.
Any other cancer from which the patient has been disease-free for three years.
Adequately managed stage I or II well differentiated thyroid or prostate cancer is also eligible, wherein the patient is not required to be in complete remission.

Show all 15Show fewer

Phase II only: patients with colorectal cancer with known MSI-high disease who have not previously been treated with immunotherapy or who have refused treatment with immunotherapy.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC102 or TMZ.
Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 3 months following the last dose of study drug.
HIV-positive patients on combination antiretroviral therapy are ineligible because of possible pharmacokinetic (PK) interactions with TRC102.
(Healthy volunteer blood donors)
Please note: healthy adult volunteers will no longer be recruited to provide blood for this study as we will no longer perform the hemolysis analysis.
Age greater than 18 years; hemoglobin greater than or equal to 12 g/dL; no history of bleeding problems; not taking aspirin or any medication that may affect erythrocyte biochemistry
Willingness to sign the healthy volunteer informed consent form.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase I/II Trial of TRC102 (Methoxyamine HCl) in Combination With Temozolomide in Patients With Relapsed Solid Tumors and Lymphomas

Background:

Methoxyamine hydrochloride (TRC102) is a new cancer treatment drug that may help improve the results of chemotherapy. It blocks tumor cells' attempts to repair damaged deoxyribonucleic acid (DNA), which may allow chemotherapy to kill the cells more easily. Researchers want to see how well it works with temozolomide, a chemotherapy drug that is designed to damage tumor cell DNA. These drugs will be given to people who have advanced solid tumors or lymphomas that have not responded to earlier treatments.

Objectives:

To test the safety and effectiveness of TRC102 and temozolomide for advanced solid tumors and lymphomas.

Eligibility:

Individuals at least 18 years of age who have advanced solid tumors or lymphomas that have not responded to earlier treatments.

Design:

Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor samples may also be collected. The size and location of the tumors will be determined with imaging studies.
Participants will take TRC102 and temozolomide for 28-day cycles of treatment. They will take temozolomide and TRC 102 by mouth once a day on days 1-5. Participants will keep a diary to record doses and any side effects.
Treatment will be monitored with frequent blood tests and imaging studies. Tumor samples will also be collected.
Participants will continue their treatment as long as the cancer does not grow and there are no severe side effects.

Read the detailed description

Background:

Base excision repair (BER) of deoxyribonucleic acid (DNA) repair pathway has been implicated in resistance to both alkylating and antimetabolite chemotherapy.
TRC102 (methoxyamine hydrochloride (HCl) acts through a novel mechanism to inhibit BER and has demonstrated the ability to potentiate the activity of the alkylating agent temozolomide (TMZ), in vitro and in vivo. We hypothesize that TRC102 can be safely co-administered with TMZ and would potentiate DNA damage caused by TMZ, resulting in antitumor responses.
Based on responses measured during the Phase I portion of the trial, we will further explore the efficacy of this combination in patients with metastatic colon carcinoma, non-small cell lung cancer (NSCLC), and granulosa cell ovarian cancer

Primary Objective:

To establish the safety, tolerability, and maximum tolerated dose (MTD) of oral TRC102 in combination with oral TMZ in patients with refractory solid tumors
Evaluate the pharmacokinetic (PK) profile of oral TRC102 when administered in combination with TMZ.
To explore the response rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer

Secondary Objective:

-To explore the progression free survival rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer

Exploratory Objectives:

Investigate tumor genomic and transcriptomic alterations potentially associated with sensitivity and/or the development of resistance to TRC102 and temozolomide.
Determine the effects of the study treatment on the level of histone gamma-H2A histone family member X (H2AX) in circulating tumor cells (CTCs) and tumor and correlate the gamma-H2AX response in tumor and CTCs
Determine the effects of the study treatment on the levels of cleaved caspase 3, epithelial- mesenchymal transition, and abdominoperineal excision (APE) in tumor and CTCs
Determine and characterize the effects of study treatment on erythrocytes
Characterize the clinical presentation of hemolysis observed in earlier study subjects and explore the possible mechanisms

Eligibility:

Phase I: histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Phase II: histologically confirmed adenocarcinoma of the colon post at least two lines of therapy, NSCLC post at least two lines of therapy, or granulosa cell ovarian cancer post at least one line of therapy
No major surgery, radiation, or chemotherapy within 4 weeks prior to entering the study
Adequate organ function
Healthy adult volunteers greater than or equal to 18 years of age will be consented to donate research blood

Please note: healthy adult volunteers will no longer be recruited to provide blood for this study as we will no longer perform the hemolysis analysis.

Study Design: Phase I

This is an open-label Phase I trial; traditional 3+3 design.
Oral TRC102 and oral TMZ will be administered daily, days 1-5 in 28-day cycles
Once the MTD is established, up to 15 additional patients will be enrolled at the MTD to further evaluate that dose for PK and pharmacodynamic (PD) endpoints for evidence of DNA damage and apoptosis.
During the escalation phase, tumor biopsies will be optional. During the expansion phase, (once MTD is reached), mandatory paired tumor biopsies will be pursued in the 15 additional patients enrolled to further evaluate progressive disease (PD) endpoints.

Phase II

This is a 3-arm Simon 2-stage design trial evaluating independently the response rate of patients with colon, NSCLC, and granulosa cell ovarian cancer.
Patients with a body surface area (BSA) of greater than or equal to 1.6 m(2) will receive 125 mg of TRC 102 and 150 mg/m(2) of TMZ PO qday x 5 every 28 days (DL6). Patients with a BSA of <1.6 m(2) will receive 100 mg of TRC 102 and 150 mg/m(2) of TMZ by mouth (PO) every (q)day x 5 every 28 days (Dose Level (DL)5). Each cycle will be 28 days.
The accrual ceiling for the Phase II portion is 75 patients.
Mandatory paired tumor biopsies will be pursued to further evaluate PD endpoints.

Conditions: Lymphomas, Solid Tumors, NSCLC, Metastatic Colon Carcinoma, Granulosa Cell Ovarian Cancer
Being tested: TRC102, CT scan, Lomotil, Prochlorperazine, Metoclopramide
Keywords: Solid Tumors, Lymphomas, DNA Damage, Pharmacodynamics, Pharmacokinetics
Medical subject headings: Lymphoma, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TRC102Drug
Also called Methoxyamine hydrochloride
Methoxyamine hydrochloride (TRC102) has been shown to potentiate the activity of temozolomide by preventing base excision repair (BER) and allowing cleavage of TRC102 bound deoxyribonucleic acid (DNA), which will cause DNA strand breaks in cancer cells. We hypothesize that oral TRC102 can be safely co-administered with Temozolomide (TMZ) and would potentiate DNA damage caused by TMZ resulting in antitumor responses.
CT scanDiagnostic test
Also called Computed tomography
CT scans will be performed at baseline, and repeat scans will be performed every 2 cycles (every 3 cycles for participants on study more than one year).
LomotilOther
Also called Diphenoxylate hydrocholoride
If diarrhea develops and does not have an identifiable cause other than study drug administration, anti-diarrheal's such as Lomotil (diphenoxylate hydrochloride (HCl) 2.5 mg + atropine sulfate 0.025 mg/tablet) dosed according to package insert or loperamide 4 mg by mouth (po) after the first unformed stool with 2 mg po every 2 hours as long as unformed stools continue (4 mg every 4 hours while asleep). No more than 16 mg of loperamide should be taken in during a 24-hour period.
ProchlorperazineOther
Also called Compro
If a participant develops nausea/vomiting, an anti-emetic such as prochlorperazine may be given.
MetoclopramideOther
Also called Reglan
If a participant develops nausea/vomiting, an anti-emetic such as metoclopramide may be given.
5-HT3 antagonistOther
Also called 5-hydroxytryptamine
If a participant develops nausea/vomiting, an anti-emetic such as 5-HT3 antagonist may be given.
AprepitantOther
Also called Emend
If a participant develops nausea/vomiting, an anti-emetic such as aprepitant may be given.
BiopsyProcedure or surgery
Tumor biopsies will be optional during the escalation phase.

Study groups in NCT01851369
Study group	Role	What they receive
Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)	Experimental	Combination treatment with oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ) for days 1-5 of 28-day cycles. Receives: Drug: TRC102; Diagnostic Test: CT scan; Other: Lomotil; Other: Prochlorperazine; Other: Metoclopramide; Other: 5-HT3 antagonist; Other: Aprepitant; Procedure: Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

Phase 2: Response Rate of This Combination in Participants With Colon Cancer, Non-small Cell Lung Cancer (NSCLC), and Granulosa Cell Ovarian Cancer
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on-study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.
Measured: Response rate at one year
The Number of Dose Limiting Toxicities Observed in Participants Receiving Oral TRC102 in Combination With Oral TMZ
Dose-limiting toxicities (DLTs) are defined as toxicities occurring within the first cycle of treatment felt to be possibly, probably, or definitely related to administration of study drugs and fulfilling one of the following criteria: Grade 4 neutropenia, febrile neutropenia, neutropenic infection: Grade ≥ 3 neutropenia with grade ≥ 3 infection, Grade ≥ 3 thrombocytopenia, a drop in hemoglobin (Hgb) ≥3.0 g/dL over one week, and all Grade ≥ 3 non-hematologic toxicity other than: non-bloody diarrhea Grade 3 that is corrected to Grade ≤ 2 within 24 hours, nausea and vomiting Grade 3 that is corrected to Grade ≤ 1 within 24 hours, creatinine Grade 3 corrected to Grade ≤ 1 within 48 hours, and Grade 3 electrolyte abnormalities. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.
Measured: At dose-limiting toxicity (DLT) determined in the first cycle; approximately 28 days
Phase 1 Pharmacokinetic (PK) Profile of Oral TRC102 When Administered in Combination With Temozolomide (TMZ) as Measured by Maximum Plasma Concentration (Cmax) of TRC102: Mean (Standard Deviation)
Blood samples will be collected, and pharmacokinetics will be assessed in the phase I portion of the study. Samples will be analyzed using a validated LC-MS or LC-MS/MS method in human plasma. The maximum observed analyte concentration in plasma was reported.
Measured: First 5 days of treatment
Phase 1 Pharmacokinetic (PK) Profile: the Percentage of TRC102 Dose Recovered From Participant Urine in Participants Treated With Oral TRC102 in Combination With Temozolomide (TMZ)
Urine samples will be collected, and pharmacokinetics will be assessed in phase I portion of the study. Samples will be analyzed using a validated liquid chromatography-mass spectrometry (LC-MS) or liquid chromatography with tandem mass spectrometry (LC-MS-MS) method.
Measured: First day of treatment
Phase 1 Maximum Tolerated Dose (MTD) of Oral TRC102 in Participants With Refractory Solid Tumors.
The MTD or recommended Phase II dose is the dose level at which no more than 1 of 6 participants experience dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤ 6) participants have DLT as a result of the drug. DLTs are defined as toxicities occurring within the first cycle of treatment felt to be possibly, probably, or definitely related to administration of study drugs and fulfilling one of the following criteria: Grade 4 neutropenia, febrile neutropenia, neutropenic infection: Grade ≥ 3 neutropenia with grade ≥ 3 infection, Grade ≥ 3 thrombocytopenia, a drop in hemoglobin (Hgb) ≥3.0 g/dL over one week, and all Grade ≥ 3 non-hematologic toxicities other than: non-bloody diarrhea Grade 3 that is corrected to Grade ≤ 2 within 24 hours, nausea and vomiting Grade 3 that is corrected to Grade ≤ 1 within 24 hours, creatinine Grade 3 corrected to Grade ≤ 1 within 48 hours, and Grade 3 electrolyte abnormalities.
Measured: First cycle of treatment; approximately 28 days
Phase 1 Maximum Tolerated Dose (MTD) of Oral Temozolomide (TMZ) in Participants With Refractory Solid Tumors.
The MTD or recommended Phase II dose is the dose level at which no more than 1 of 6 participants experience dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤ 6) participants have DLT as a result of the drug. DLTs will be defined as toxicities occurring within the first cycle of treatment and is felt to be possibly, probably, or definitely related to administration of study drugs and fulfills one of the following criteria: hematologic toxicities - Grade 4 neutropenia, febrile neutropenia, neutropenic infection: Grade ≥ 3 neutropenia with grade ≥ 3 infection, Grade ≥ 3 thrombocytopenia, a drop in hemoglobin (Hgb) ≥3.0 g/dL over one week, any degree of lymphopenia, or leukopenia in the absence of grade 4 neutropenia will not be considered dose limiting, and Grade ≥ 3 non-hematologic toxicity. Grade ≥ 3 electrolyte abnormalities will not be considered dose limiting.
Measured: First cycle of treatment; approximately 28 days

Secondary outcomes (1)

Phase 2: Progression Free Survival Rate of This Combination in Participants With Colon Cancer, Non-small Cell Lung Cancer (NSCLC), and Granulosa Cell Ovarian Cancer
Progression free survival rate of this combination in participants with colon cancer, NSCLC, and granulosa cell ovarian cancer. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum onstudy (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.
Measured: Duration on study, an average of 130 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Jul 20131 Aug 2023

First posted10 May 2013 (estimated)
Study start12 Jul 2013
Primary completion1 Aug 2023
Study completion1 Aug 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for LymphomasStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 93 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01851369
Sponsor's protocol ID: 130118
Other IDs: 13-C-0118
Status last verified: Apr 2024
First submitted: 8 May 2013
Last updated: 8 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Publications

Liu L, Nakatsuru Y, Gerson SL. Base excision repair as a therapeutic target in colon cancer. Clin Cancer Res. 2002 Sep;8(9):2985-91.
PubMed 12231545
Yan L, Bulgar A, Miao Y, Mahajan V, Donze JR, Gerson SL, Liu L. Combined treatment with temozolomide and methoxyamine: blocking apurininc/pyrimidinic site repair coupled with targeting topoisomerase IIalpha. Clin Cancer Res. 2007 Mar 1;13(5):1532-9. doi: 10.1158/1078-0432.CCR-06-1595.
PubMed 17332299
Kinders RJ, Hollingshead M, Lawrence S, Ji J, Tabb B, Bonner WM, Pommier Y, Rubinstein L, Evrard YA, Parchment RE, Tomaszewski J, Doroshow JH; National Cancer Institute Phase 0 Clinical Trials Team. Development of a validated immunofluorescence assay for gammaH2AX as a pharmacodynamic marker of topoisomerase I inhibitor activity. Clin Cancer Res. 2010 Nov 15;16(22):5447-57. doi: 10.1158/1078-0432.CCR-09-3076. Epub 2010 Oct 5.
PubMed 20924131

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Trial of TRC102 (Methoxyamine HCl) in Combination With Temozolomide in Patients With Relapsed Solid Tumors and Lymphomas
ClinicalTrials.gov ID: NCT01851369
Acronym / sponsor ID: 130118
Conditions: Lymphomas, Solid Tumors, NSCLC, Metastatic Colon Carcinoma, Granulosa Cell Ovarian Cancer
Keywords: Solid Tumors, Lymphomas, DNA Damage, Pharmacodynamics, Pharmacokinetics
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 93 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 12 Jul 2013 (actual)
Primary completion: 1 Aug 2023 (actual)
Study completion: 1 Aug 2023 (actual)
First posted: 10 May 2013 (estimated)
Results: Posted 8 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

Methoxyamine hydrochloride (TRC102) is a new cancer treatment drug that may help improve the results of chemotherapy. It blocks tumor cells' attempts to repair damaged deoxyribonucleic acid (DNA), which may allow chemotherapy to kill the cells more easily. Researchers want to see how well it works with temozolomide, a chemotherapy drug that is designed to damage tumor cell DNA. These drugs will be given to people who have advanced solid tumors or lymphomas that have not responded to earlier treatments.

Objectives:

To test the safety and effectiveness of TRC102 and temozolomide for advanced solid tumors and lymphomas.

Eligibility:

Individuals at least 18 years of age who have advanced solid tumors or lymphomas that have not responded to earlier treatments.

Design:

Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Tumor samples may also be collected. The size and location of the tumors will be determined with imaging studies.
Participants will take TRC102 and temozolomide for 28-day cycles of treatment. They will take temozolomide and TRC 102 by mouth once a day on days 1-5. Participants will keep a diary to record doses and any side effects.
Treatment will be monitored with frequent blood tests and imaging studies. Tumor samples will also be collected.
Participants will continue their treatment as long as the cancer does not grow and there are no severe side effects.

Detailed description

Background:

Base excision repair (BER) of deoxyribonucleic acid (DNA) repair pathway has been implicated in resistance to both alkylating and antimetabolite chemotherapy.
TRC102 (methoxyamine hydrochloride (HCl) acts through a novel mechanism to inhibit BER and has demonstrated the ability to potentiate the activity of the alkylating agent temozolomide (TMZ), in vitro and in vivo. We hypothesize that TRC102 can be safely co-administered with TMZ and would potentiate DNA damage caused by TMZ, resulting in antitumor responses.
Based on responses measured during the Phase I portion of the trial, we will further explore the efficacy of this combination in patients with metastatic colon carcinoma, non-small cell lung cancer (NSCLC), and granulosa cell ovarian cancer

Primary Objective:

To establish the safety, tolerability, and maximum tolerated dose (MTD) of oral TRC102 in combination with oral TMZ in patients with refractory solid tumors
Evaluate the pharmacokinetic (PK) profile of oral TRC102 when administered in combination with TMZ.
To explore the response rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer

Secondary Objective:

-To explore the progression free survival rate of this combination in patients with colon cancer, NSCLC, and granulosa cell ovarian cancer

Exploratory Objectives:

Investigate tumor genomic and transcriptomic alterations potentially associated with sensitivity and/or the development of resistance to TRC102 and temozolomide.
Determine the effects of the study treatment on the level of histone gamma-H2A histone family member X (H2AX) in circulating tumor cells (CTCs) and tumor and correlate the gamma-H2AX response in tumor and CTCs
Determine the effects of the study treatment on the levels of cleaved caspase 3, epithelial- mesenchymal transition, and abdominoperineal excision (APE) in tumor and CTCs
Determine and characterize the effects of study treatment on erythrocytes
Characterize the clinical presentation of hemolysis observed in earlier study subjects and explore the possible mechanisms

Eligibility:

Phase I: histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Phase II: histologically confirmed adenocarcinoma of the colon post at least two lines of therapy, NSCLC post at least two lines of therapy, or granulosa cell ovarian cancer post at least one line of therapy
No major surgery, radiation, or chemotherapy within 4 weeks prior to entering the study
Adequate organ function
Healthy adult volunteers greater than or equal to 18 years of age will be consented to donate research blood

Please note: healthy adult volunteers will no longer be recruited to provide blood for this study as we will no longer perform the hemolysis analysis.

Study Design: Phase I

This is an open-label Phase I trial; traditional 3+3 design.
Oral TRC102 and oral TMZ will be administered daily, days 1-5 in 28-day cycles
Once the MTD is established, up to 15 additional patients will be enrolled at the MTD to further evaluate that dose for PK and pharmacodynamic (PD) endpoints for evidence of DNA damage and apoptosis.
During the escalation phase, tumor biopsies will be optional. During the expansion phase, (once MTD is reached), mandatory paired tumor biopsies will be pursued in the 15 additional patients enrolled to further evaluate progressive disease (PD) endpoints.

Phase II

This is a 3-arm Simon 2-stage design trial evaluating independently the response rate of patients with colon, NSCLC, and granulosa cell ovarian cancer.
Patients with a body surface area (BSA) of greater than or equal to 1.6 m(2) will receive 125 mg of TRC 102 and 150 mg/m(2) of TMZ PO qday x 5 every 28 days (DL6). Patients with a BSA of <1.6 m(2) will receive 100 mg of TRC 102 and 150 mg/m(2) of TMZ by mouth (PO) every (q)day x 5 every 28 days (Dose Level (DL)5). Each cycle will be 28 days.
The accrual ceiling for the Phase II portion is 75 patients.
Mandatory paired tumor biopsies will be pursued to further evaluate PD endpoints.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)	Experimental	Drug: TRC102, Diagnostic Test: CT scan, Other: Lomotil, Other: Prochlorperazine, Other: Metoclopramide, Other: 5-HT3 antagonist, Other: Aprepitant, Procedure: BiopsyCombination treatment with oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ) for days 1-5 of 28-day cycles.

Who may qualify

Ages: 18 to 120 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (0 listed)

Key exclusion criteria (15 listed)

Patients who are actively receiving any other investigational agents.
Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for greater than or equal to 4 weeks without requiring steroid and anti-seizure medications are eligible to participate.
Phase II only: No other prior malignancies are allowed except for the following:
Phase II only: patients with colorectal cancer with known MSI-high disease who have not previously been treated with immunotherapy or who have refused treatment with immunotherapy.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC102 or TMZ.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TRC102Also: Methoxyamine hydrochlorideMethoxyamine hydrochloride (TRC102) has been shown to potentiate the activity of temozolomide by preventing base excision repair (BER) and allowing cleavage of TRC102 bound deoxyribonucleic acid (DNA), which will cause DNA strand breaks in cancer cells. We hypothesize that oral TRC102 can be safely co-administered with Temozolomide (TMZ) and would potentiate DNA damage caused by TMZ resulting in antitumor responses.	Drug	Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)
CT scanAlso: Computed tomographyCT scans will be performed at baseline, and repeat scans will be performed every 2 cycles (every 3 cycles for participants on study more than one year).	Diagnostic test	Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)
LomotilAlso: Diphenoxylate hydrocholorideIf diarrhea develops and does not have an identifiable cause other than study drug administration, anti-diarrheal's such as Lomotil (diphenoxylate hydrochloride (HCl) 2.5 mg + atropine sulfate 0.025 mg/tablet) dosed according to package insert or loperamide 4 mg by mouth (po) after the first unformed stool with 2 mg po every 2 hours as long as unformed stools continue (4 mg every 4 hours while asleep). No more than 16 mg of loperamide should be taken in during a 24-hour period.	Other	Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)
ProchlorperazineAlso: ComproIf a participant develops nausea/vomiting, an anti-emetic such as prochlorperazine may be given.	Other	Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)
MetoclopramideAlso: ReglanIf a participant develops nausea/vomiting, an anti-emetic such as metoclopramide may be given.	Other	Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)
5-HT3 antagonistAlso: 5-hydroxytryptamineIf a participant develops nausea/vomiting, an anti-emetic such as 5-HT3 antagonist may be given.	Other	Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)
AprepitantAlso: EmendIf a participant develops nausea/vomiting, an anti-emetic such as aprepitant may be given.	Other	Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)
BiopsyTumor biopsies will be optional during the escalation phase.	Procedure or surgery	Combination Treatment with Oral methoxyamine hydrochloride (TRC102) and oral Temozolomide (TMZ)

Primary outcome

Phase 2: Response Rate of This Combination in Participants With Colon Cancer, Non-small Cell Lung Cancer (NSCLC), and Granulosa Cell Ovarian Cancer
Time frame: Response rate at one year
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on-study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.
The Number of Dose Limiting Toxicities Observed in Participants Receiving Oral TRC102 in Combination With Oral TMZ
Time frame: At dose-limiting toxicity (DLT) determined in the first cycle; approximately 28 days
Dose-limiting toxicities (DLTs) are defined as toxicities occurring within the first cycle of treatment felt to be possibly, probably, or definitely related to administration of study drugs and fulfilling one of the following criteria: Grade 4 neutropenia, febrile neutropenia, neutropenic infection: Grade ≥ 3 neutropenia with grade ≥ 3 infection, Grade ≥ 3 thrombocytopenia, a drop in hemoglobin (Hgb) ≥3.0 g/dL over one week, and all Grade ≥ 3 non-hematologic toxicity other than: non-bloody diarrhea Grade 3 that is corrected to Grade ≤ 2 within 24 hours, nausea and vomiting Grade 3 that is corrected to Grade ≤ 1 within 24 hours, creatinine Grade 3 corrected to Grade ≤ 1 within 48 hours, and Grade 3 electrolyte abnormalities. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.
Phase 1 Pharmacokinetic (PK) Profile of Oral TRC102 When Administered in Combination With Temozolomide (TMZ) as Measured by Maximum Plasma Concentration (Cmax) of TRC102: Mean (Standard Deviation)
Time frame: First 5 days of treatment
Blood samples will be collected, and pharmacokinetics will be assessed in the phase I portion of the study. Samples will be analyzed using a validated LC-MS or LC-MS/MS method in human plasma. The maximum observed analyte concentration in plasma was reported.
Phase 1 Pharmacokinetic (PK) Profile: the Percentage of TRC102 Dose Recovered From Participant Urine in Participants Treated With Oral TRC102 in Combination With Temozolomide (TMZ)
Time frame: First day of treatment
Urine samples will be collected, and pharmacokinetics will be assessed in phase I portion of the study. Samples will be analyzed using a validated liquid chromatography-mass spectrometry (LC-MS) or liquid chromatography with tandem mass spectrometry (LC-MS-MS) method.
Phase 1 Maximum Tolerated Dose (MTD) of Oral TRC102 in Participants With Refractory Solid Tumors.
Time frame: First cycle of treatment; approximately 28 days
The MTD or recommended Phase II dose is the dose level at which no more than 1 of 6 participants experience dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤ 6) participants have DLT as a result of the drug. DLTs are defined as toxicities occurring within the first cycle of treatment felt to be possibly, probably, or definitely related to administration of study drugs and fulfilling one of the following criteria: Grade 4 neutropenia, febrile neutropenia, neutropenic infection: Grade ≥ 3 neutropenia with grade ≥ 3 infection, Grade ≥ 3 thrombocytopenia, a drop in hemoglobin (Hgb) ≥3.0 g/dL over one week, and all Grade ≥ 3 non-hematologic toxicities other than: non-bloody diarrhea Grade 3 that is corrected to Grade ≤ 2 within 24 hours, nausea and vomiting Grade 3 that is corrected to Grade ≤ 1 within 24 hours, creatinine Grade 3 corrected to Grade ≤ 1 within 48 hours, and Grade 3 electrolyte abnormalities.
Phase 1 Maximum Tolerated Dose (MTD) of Oral Temozolomide (TMZ) in Participants With Refractory Solid Tumors.
Time frame: First cycle of treatment; approximately 28 days
The MTD or recommended Phase II dose is the dose level at which no more than 1 of 6 participants experience dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤ 6) participants have DLT as a result of the drug. DLTs will be defined as toxicities occurring within the first cycle of treatment and is felt to be possibly, probably, or definitely related to administration of study drugs and fulfills one of the following criteria: hematologic toxicities - Grade 4 neutropenia, febrile neutropenia, neutropenic infection: Grade ≥ 3 neutropenia with grade ≥ 3 infection, Grade ≥ 3 thrombocytopenia, a drop in hemoglobin (Hgb) ≥3.0 g/dL over one week, any degree of lymphopenia, or leukopenia in the absence of grade 4 neutropenia will not be considered dose limiting, and Grade ≥ 3 non-hematologic toxicity. Grade ≥ 3 electrolyte abnormalities will not be considered dose limiting.

1 secondary outcome

Phase 2: Progression Free Survival Rate of This Combination in Participants With Colon Cancer, Non-small Cell Lung Cancer (NSCLC), and Granulosa Cell Ovarian Cancer
Time frame: Duration on study, an average of 130 days

Results and safety

Results posted to the registry on 8 May 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase (Ph) 1 Dose Level -2 Methoxyamine (TRC102) 25mg & Temozolomide (TMZ) 75mg/m^2	0	0
Phase 1 Dose Level -1 Methoxyamine (TRC102) 25mg & Temozolomide 100mg/m^2	0	0
Phase 1 Solid Tumor Dose Level 1 Methoxyamine (TRC102) 125mg & Temozolomide 75mg/m^2	3	3
Phase 1 Solid Tumor Dose Level 2 Methoxyamine (TRC102) 50mg & Temozolomide 125mg/m^2	6	6
Phase 1 Solid Tumor Dose Level 3 Methoxyamine (TRC102) 50mg & Temozolomide 150mg/m^2	4	4
Phase 1 Solid Tumor Dose Level 4 Methoxyamine (TRC102) 75mg & Temozolomide 150mg/m^2	8	7
Phase 1 Solid Tumor Dose Level 5 Methoxyamine (TRC102) 100mg & Temozolomide 150mg/m^2	3	3
Phase 1 Solid Tumor Dose Level 6 Methoxyamine (TRC102) 125mg & Temozolomide 150mg/m^2	3	3
Phase 1 Solid Tumor Dose Level 7 Methoxyamine (TRC102) 150mg & Temozolomide 150mg/m^2	5	5
Phase 1 Solid Tumor Dose Level 8 Methoxyamine (TRC102) 150mg & Temozolomide 200mg/m^2	3	3
Ph 2 Colorectal Cancer TMZ 150mg/m^2/Methoxyamine 125mgOR100mg(Based on Body Surface Area)	0	0
Ph2 Non Small Cell Lung Cancer TMZ 150mg/m^2/Methoxyamine125mgOR100mg(Based on Body Surface Area)	0	0
Ph 2 Granulosa Cell Temozolomide 150mg/m^2 & Methoxyamine 125mgOR 100mg (Based on Body Surface Area)	0	0

Primary outcome: Phase 2: Response Rate of This Combination in Participants With Colon Cancer, Non-small Cell Lung Cancer (NSCLC), and Granulosa Cell Ovarian Cancer

Time frame: Response rate at one year. Count of participants. Unit: Participants

Measure	Ph 2 Colorectal Cancer TMZ 150mg/m^2/Methoxyamine 125mgOR100mg(Based on Body Surface Area) n = 16	Ph2 Non Small Cell Lung Cancer TMZ 150mg/m^2/Methoxyamine125mgOR100mg(Based on Body Surface Area) n = 16	Ph 2 Granulosa Cell Temozolomide 150mg/m^2 & Methoxyamine 125mgOR 100mg (Based on Body Surface Area) n = 9
Complete Response	0	0	0
Partial Response	1	0	0
Stable Disease	3	10	5
Progressive Disease	8	3	2
Not Assessed Due to Death on Study	1	0	0
Not Assessed Due to Clinical Progression	2	2	1
Not Assessed Due to Refusing Further Treatment	1	1	1

Population analysed: A total of 41/93 participants were analyzed: 0/52 phase 1 participants were analyzed as this outcome measure was for the phase 2 participants only; 41/41 phase 2 participants were evaluable for response rate.

Primary outcome: The Number of Dose Limiting Toxicities Observed in Participants Receiving Oral TRC102 in Combination With Oral TMZ

Time frame: At dose-limiting toxicity (DLT) determined in the first cycle; approximately 28 days. Number. Unit: Dose limiting toxicities

Measure	Phase 1 Solid Tumor Dose Level 2 Methoxyamine (TRC102) 50mg & Temozolomide 125mg/m^2 n = 6	Phase 1 Solid Tumor Dose Level 4 Methoxyamine (TRC102) 75mg & Temozolomide 150mg/m^2 n = 7	Phase 1 Solid Tumor Dose Level 8 Methoxyamine (TRC102) 150mg & Temozolomide 200mg/m^2 n = 3
A Drop in Hemoglobin (Hgb) ≥3.0 g/dL Over One Week	1	0	2
Grade 4 Neutropenia	0	1	1
Grade 4 Thrombocytopenia	0	1	1

Population analysed: 36/37 participants in the phase I dose escalation cohort were analyzed because one participant in dose level 3 declined to participate (before treatment started).

Primary outcome: Phase 1 Pharmacokinetic (PK) Profile of Oral TRC102 When Administered in Combination With Temozolomide (TMZ) as Measured by Maximum Plasma Concentration (Cmax) of TRC102: Mean (Standard Deviation)

Time frame: First 5 days of treatment. Mean (Standard Deviation). Unit: Micromolar (µM)

Measure	Phase 1 Solid Tumor Dose Level 1 Methoxyamine (TRC102) 125mg & Temozolomide 75mg/m^2 n = 3	Phase 1 Solid Tumor Dose Level 2 Methoxyamine (TRC102) 50mg & Temozolomide 125mg/m^2 n = 6	Phase 1 Solid Tumor Dose Level 3 Methoxyamine (TRC102) 50mg & Temozolomide 150mg/m^2 n = 4	Phase 1 Solid Tumor Dose Level 4 Methoxyamine (TRC102) 75mg & Temozolomide 150mg/m^2 n = 7	Phase 1 Solid Tumor Dose Level 5 Methoxyamine (TRC102) 100mg & Temozolomide 150mg/m^2 n = 3	Phase 1 Solid Tumor Dose Level 6 Methoxyamine (TRC102) 125mg & Temozolomide 150mg/m^2 n = 10	Phase 1 Solid Tumor Dose Level 7 Methoxyamine (TRC102) 150mg & Temozolomide 150mg/m^2 n = 15	Phase 1 Solid Tumor Dose Level 8 Methoxyamine (TRC102) 150mg & Temozolomide 200mg/m^2 n = 3
Value	0.75 (0.49)	1.49 (1.07)	0.97 (0.27)	2.36 (2.68)	3.51 (2.52)	7.11 (8.21)	7.45 (5.39)	7.54 (5.40)

Population analysed: 51/52 participants were analyzed for plasma PK in phase 1 because one participant declined to participate (before treatment started).

Primary outcome: Phase 1 Pharmacokinetic (PK) Profile: the Percentage of TRC102 Dose Recovered From Participant Urine in Participants Treated With Oral TRC102 in Combination With Temozolomide (TMZ)

Time frame: First day of treatment. Mean (Standard Deviation). Unit: Percentage

Measure	Phase 1 Solid Tumor Dose Level 1 Methoxyamine (TRC102) 125mg & Temozolomide 75mg/m^2 n = 3	Phase 1 Solid Tumor Dose Level 2 Methoxyamine (TRC102) 50mg & Temozolomide 125mg/m^2 n = 6	Phase 1 Solid Tumor Dose Level 3 Methoxyamine (TRC102) 50mg & Temozolomide 150mg/m^2 n = 4	Phase 1 Solid Tumor Dose Level 4 Methoxyamine (TRC102) 75mg & Temozolomide 150mg/m^2 n = 7	Phase 1 Solid Tumor Dose Level 5 Methoxyamine (TRC102) 100mg & Temozolomide 150mg/m^2 n = 3	Phase 1 Solid Tumor Dose Level 6 Methoxyamine (TRC102) 125mg & Temozolomide 150mg/m^2 n = 10	Phase 1 Solid Tumor Dose Level 7 Methoxyamine (TRC102) 150mg & Temozolomide 150mg/m^2 n = 15	Phase 1 Solid Tumor Dose Level 8 Methoxyamine (TRC102) 150mg & Temozolomide 200mg/m^2 n = 3
Value	1.6 (1.2)	0.8 (0.3)	0.8 (0.5)	2.5 (2.9)	4.0 (3.1)	4.8 (5.2)	4.1 (4.6)	3.8 (2.3)

Population analysed: 51/52 participants were analyzed for urine PK in phase 1 because one participant declined to participate (before treatment started).

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Date treatment consent signed to date off study, an average of 115 days.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1 Solid Tumor Dose Level 1 Methoxyamine (TRC102) 125mg & Temozolomide 75mg/m^2	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Phase 1 Solid Tumor Dose Level 2 Methoxyamine (TRC102) 50mg & Temozolomide 125mg/m^2	3 of 6 (50%)	6 of 6 (100%)	0 of 6
Phase 1 Solid Tumor Dose Level 3 Methoxyamine (TRC102) 50mg & Temozolomide 150mg/m^2	2 of 4 (50%)	4 of 4 (100%)	0 of 4
Phase 1 Solid Tumor Dose Level 4 Methoxyamine (TRC102) 75mg & Temozolomide 150mg/m^2	1 of 7 (14.3%)	7 of 7 (100%)	0 of 7
Phase 1 Solid Tumor Dose Level 5 Methoxyamine (TRC102) 100mg & Temozolomide 150mg/m^2	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Phase 1 Solid Tumor Dose Level 6 Methoxyamine (TRC102) 125mg & Temozolomide 150mg/m^2	4 of 10 (40%)	10 of 10 (100%)	2 of 10
Phase 1 Solid Tumor Dose Level 7 Methoxyamine (TRC102) 150mg & Temozolomide 150mg/m^2	9 of 15 (60%)	15 of 15 (100%)	2 of 15
Phase 1 Solid Tumor Dose Level 8 Methoxyamine (TRC102) 150mg & Temozolomide 200mg/m^2	2 of 3 (66.7%)	3 of 3 (100%)	0 of 3
Ph 2 Colorectal Cancer TMZ 150mg/m^2/Methoxyamine 125mgOR100mg(Based on Body Surface Area)	9 of 16 (56.3%)	16 of 16 (100%)	1 of 16
Ph2 Non Small Cell Lung Cancer TMZ 150mg/m^2/Methoxyamine125mgOR100mg(Based on Body Surface Area)	9 of 16 (56.3%)	16 of 16 (100%)	0 of 16
Ph 2 Granulosa Cell Temozolomide 150mg/m^2 & Methoxyamine 125mgOR 100mg (Based on Body Surface Area)	2 of 9 (22.2%)	9 of 9 (100%)	1 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 12231545Liu L, Nakatsuru Y, Gerson SL. Base excision repair as a therapeutic target in colon cancer. Clin Cancer Res. 2002 Sep;8(9):2985-91.
Background: PubMed 17332299Yan L, Bulgar A, Miao Y, Mahajan V, Donze JR, Gerson SL, Liu L. Combined treatment with temozolomide and methoxyamine: blocking apurininc/pyrimidinic site repair coupled with targeting topoisomerase IIalpha. Clin Cancer Res. 2007 Mar 1;13(5):1532-9. doi: 10.1158/1078-0432.CCR-06-1595.
Background: PubMed 20924131Kinders RJ, Hollingshead M, Lawrence S, Ji J, Tabb B, Bonner WM, Pommier Y, Rubinstein L, Evrard YA, Parchment RE, Tomaszewski J, Doroshow JH; National Cancer Institute Phase 0 Clinical Trials Team. Development of a validated immunofluorescence assay for gammaH2AX as a pharmacodynamic marker of topoisomerase I inhibitor activity. Clin Cancer Res. 2010 Nov 15;16(22):5447-57. doi: 10.1158/1078-0432.CCR-09-3076. Epub 2010 Oct 5.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alice P Chen, M.D. principal investigator

National Cancer Institute (NCI)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TRC102, CT scan and Lomotil in people with Lymphomas and Solid Tumors, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 2: Response Rate of This Combination in Participants With Colon Cancer, Non-small Cell Lung Cancer (NSCLC), and Granulosa Cell Ovarian Cancer (time frame: Response rate at one year). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01851369, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.