Metastatic CancerPhase 1NCT02049593
PARP Inhibitor BMN-673 and Temozolomide or Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic Solid Tumors
A Phase 1 study testing PARP inhibitor BMN-673, temozolomide and irinotecan hydrochloride in people with Metastatic Cancer and Unspecified Adult Solid Tumor, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
This phase I trial studies the side effects and the best dose of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor BMN-673 when given together with temozolomide or irinotecan hydrochloride in treating patients with locally advanced or metastatic solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Cancer, Unspecified Adult Solid Tumor
- What is being tested?
- PARP inhibitor BMN-673, temozolomide and irinotecan hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2014to 7 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST, v1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT may be =< 5 x ULN
- Total serum bilirubin =< 1.5 x ULN
- Calculated creatinine clearance of >= 40 ml/min; as per Cockcroft-Gault formula
Show all 13Show fewer
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1500/mm^3
- Platelet count >= 100,000/mm^3
- Able to take oral medications
- Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
- Sexually active patients must be willing to use an acceptable method of contraception such as double barrier contraception during treatment and for 30 days after the last dose of BMN 673
- Females of childbearing potential must have a negative serum pregnancy test at screening
Who cannot join
- Has not recovered (recovery is defined as National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE version (v)4.03] grade =< 1) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting the inclusion requirements stated in the inclusion criterion
- Prior treatment with a PARP inhibitor
- Prior allergic reaction or severe intolerance to either irinotecan or temozolomide
- History of central nervous system (CNS) metastasis that are untreated or not stable
- Any antitumor systemic cytotoxic therapies within 28 days prior to enrollment (6 weeks for nitrosoureas or mitomycin-C); prior high-dose chemotherapy with bone marrow or stem cell transplant is excluded
- Is known to have human immunodeficiency virus (HIV) or has active hepatitis C virus (HCV), or active hepatitis B virus (HBV)
Show all 17Show fewer
- Has had major surgery within 28 days prior to enrollment
- Active gastrointestinal tract disease with malabsorption syndrome
- Requirement for IV alimentation
- Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- Symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication (atrial fibrillation is permitted)
- Use of any investigational product or investigational medical device within 28 days prior to enrollment
- Concurrent disease or condition that would interfere with study participation or safety, such as:
- Active, clinically significant infection requiring the use of parenteral anti-microbial agents, or grade > 2 by NCI CTCAE (v 4.03) within 14 days prior to enrollment
- Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders
- Non-healing wound, ulcer, or bone fracture
- Bone marrow disorder including myelodysplasia
Trial locations and contacts
1 site in 1 country.
United States1 site
Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
About this study
Official title: Phase I Trial of BMN 673 and Selected Cytotoxics in Patients With Advanced Solid Tumors
This phase I trial studies the side effects and the best dose of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor BMN-673 when given together with temozolomide or irinotecan hydrochloride in treating patients with locally advanced or metastatic solid tumors. PARP inhibitor BMN-673 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may help temozolomide and irinotecan hydrochloride work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PARP inhibitor BMN-673 with temozolomide or irinotecan hydrochloride may be an effective treatment for patients with advanced solid tumors.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability and to estimate the maximum tolerated dose (MTD) of the following combinations in participants with advanced solid tumors: Arm A: BMN 673 (PARP inhibitor BMN-673) and temozolomide; Arm B: BMN 673 and irinotecan (irinotecan hydrochloride).
SECONDARY OBJECTIVES:
- To evaluate the pharmacokinetics of BMN 673, temozolomide, and irinotecan when BMN 673 is given in combination with temozolomide (Arm A) or irinotecan (Arm B). To assess the effects of temozolomide and irinotecan in Arms A and B respectively on the pharmacokinetics of BMN 673.
II. To evaluate biomarkers that correlate with effect of BMN 673 in combination with temozolomide or irinotecan.
III. To document any anti-tumor activity.
OUTLINE: This is a dose-escalation study of PARP inhibitor BMN-673. Patients are assigned to 1 of 2 treatment arms.
ARM A: Patients receive PARP inhibitor BMN-673 orally (PO) once daily (QD) on days 1-28 and temozolomide PO daily on days1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride intravenously (IV) on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 12 months.
- Conditions
- Metastatic Cancer, Unspecified Adult Solid Tumor
- Being tested
- PARP inhibitor BMN-673, temozolomide, irinotecan hydrochloride, pharmacological study, laboratory biomarker analysis
- Keywords
- protocol specific
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PARP inhibitor BMN-673Drug
Also called BMN 673, BMN-673
Given PO
temozolomideDrug
Also called SCH 52365, Temodal, Temodar, TMZ
Given PO
Also called Campto, Camptosar, CPT-11, irinotecan
Given IV
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A (PARP inhibitor BMN-673, temozolomide) | Experimental | Patients receive PARP inhibitor BMN-673 PO QD on days 1-28 and temozolomide PO daily on days1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: PARP inhibitor BMN-673; Drug: temozolomide; Other: pharmacological study; Other: laboratory biomarker analysis |
| Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride) | Experimental | Patients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: PARP inhibitor BMN-673; Drug: irinotecan hydrochloride; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity graded using the NCI CTCAE v. 4.03
Measured: Up to 28 days
Secondary outcomes (10)
Incidence of adverse events graded by NCI CTCAE v. 4.03
Characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy.
Measured: Up to 12 months
Levels of PARP inhibitory BMN 673
Measured: Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
levels of temozolomide
Measured: Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
Levels of irinotecan hydrochloride
Measured: Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
Biomarker levels in blood and tumor tissue
Measured: Baseline and Cycle1 Day 21 for participants undergoing biopsy (expansion phase only)
Incidence of laboratory abnormalities graded by NCI CTCAE v. 4.03
Characterized by type, frequency, severity, timing, seriousness and relationship to study therapy.
Measured: Up to 12 months
Objective tumor response assessed using RECIST v. 1.1
Sum of partial responses plus complete responses. The proportion of ever achieving a clinical response will be estimated, and an exact one-sided 90% confidence interval will be constructed to identify the likely range for the underlying tumor response rate.
Measured: Up to 12 months
Duration of response
The log rank test will be used to examine association between categorical markers and time to disease progression. Cox-proportional hazards regression models will be used to correlate quantitative markers with time to disease progression.
Measured: Time of initial response until documented tumor progression, assessed up to 12 months
Progression-free survival
Measured: Time from enrollment until objective tumor progression or death, assessed up to 12 months
Overall survival (OS)
Measured: Time from randomization until death from any cause, up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2014 (estimated)
- Study start12 Jun 2014
- Primary completion7 Oct 2019
- Study completion7 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic CancerStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive Cancer CenterThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Translational Research in Oncology, BioMarin Pharmaceutical, Medivation, Inc.
- Responsible party
- Sponsor
- Investigators
- Zev Wainberg, Principal investigator, Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02049593
- Sponsor's protocol ID
- 13-001857
- Other IDs
- NCI-2014-00048, TRIO-US GI-07
- Status last verified
- Nov 2019
- First submitted
- 27 Jan 2014
- Last updated
- 26 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of BMN 673 and Selected Cytotoxics in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02049593
- Acronym / sponsor ID
- 13-001857
- Conditions
- Metastatic Cancer, Unspecified Adult Solid Tumor
- Keywords
- protocol specific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Translational Research in Oncology, BioMarin Pharmaceutical, Medivation, Inc.
- Study start
- 12 Jun 2014 (actual)
- Primary completion
- 7 Oct 2019 (actual)
- Study completion
- 7 Oct 2019 (actual)
- First posted
- 30 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and the best dose of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor BMN-673 when given together with temozolomide or irinotecan hydrochloride in treating patients with locally advanced or metastatic solid tumors. PARP inhibitor BMN-673 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may help temozolomide and irinotecan hydrochloride work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PARP inhibitor BMN-673 with temozolomide or irinotecan hydrochloride may be an effective treatment for patients with advanced solid tumors.
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability and to estimate the maximum tolerated dose (MTD) of the following combinations in participants with advanced solid tumors: Arm A: BMN 673 (PARP inhibitor BMN-673) and temozolomide; Arm B: BMN 673 and irinotecan (irinotecan hydrochloride).
SECONDARY OBJECTIVES:
- To evaluate the pharmacokinetics of BMN 673, temozolomide, and irinotecan when BMN 673 is given in combination with temozolomide (Arm A) or irinotecan (Arm B). To assess the effects of temozolomide and irinotecan in Arms A and B respectively on the pharmacokinetics of BMN 673.
II. To evaluate biomarkers that correlate with effect of BMN 673 in combination with temozolomide or irinotecan.
III. To document any anti-tumor activity.
OUTLINE: This is a dose-escalation study of PARP inhibitor BMN-673. Patients are assigned to 1 of 2 treatment arms.
ARM A: Patients receive PARP inhibitor BMN-673 orally (PO) once daily (QD) on days 1-28 and temozolomide PO daily on days1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride intravenously (IV) on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (PARP inhibitor BMN-673, temozolomide) | Experimental | Drug: PARP inhibitor BMN-673, Drug: temozolomide, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive PARP inhibitor BMN-673 PO QD on days 1-28 and temozolomide PO daily on days1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride) | Experimental | Drug: PARP inhibitor BMN-673, Drug: irinotecan hydrochloride, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST, v1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT may be =< 5 x ULN
- Total serum bilirubin =< 1.5 x ULN
Key exclusion criteria (17 listed)
- Has not recovered (recovery is defined as National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE version (v)4.03] grade =< 1) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting the inclusion requirements stated in the inclusion criterion
- Prior treatment with a PARP inhibitor
- Prior allergic reaction or severe intolerance to either irinotecan or temozolomide
- History of central nervous system (CNS) metastasis that are untreated or not stable
- Any antitumor systemic cytotoxic therapies within 28 days prior to enrollment (6 weeks for nitrosoureas or mitomycin-C); prior high-dose chemotherapy with bone marrow or stem cell transplant is excluded
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 |
|---|---|---|
| PARP inhibitor BMN-673Also: BMN 673, BMN-673Given PO | Drug | Arm A (PARP inhibitor BMN-673, temozolomide), Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride) |
| temozolomideAlso: SCH 52365, Temodal, Temodar, TMZGiven PO | Drug | Arm A (PARP inhibitor BMN-673, temozolomide) |
| irinotecan hydrochlorideAlso: Campto, Camptosar, CPT-11, irinotecanGiven IV | Drug | Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm A (PARP inhibitor BMN-673, temozolomide), Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride) |
| laboratory biomarker analysisCorrelative studies | Other | Arm A (PARP inhibitor BMN-673, temozolomide), Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride) |
Primary outcome
Dose Limiting Toxicity graded using the NCI CTCAE v. 4.03
Time frame: Up to 28 days
10 secondary outcomes
Incidence of adverse events graded by NCI CTCAE v. 4.03
Time frame: Up to 12 months
Levels of PARP inhibitory BMN 673
Time frame: Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
levels of temozolomide
Time frame: Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
Levels of irinotecan hydrochloride
Time frame: Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
Biomarker levels in blood and tumor tissue
Time frame: Baseline and Cycle1 Day 21 for participants undergoing biopsy (expansion phase only)
Incidence of laboratory abnormalities graded by NCI CTCAE v. 4.03
Time frame: Up to 12 months
Objective tumor response assessed using RECIST v. 1.1
Time frame: Up to 12 months
Duration of response
Time frame: Time of initial response until documented tumor progression, assessed up to 12 months
Progression-free survival
Time frame: Time from enrollment until objective tumor progression or death, assessed up to 12 months
Overall survival (OS)
Time frame: Time from randomization until death from any cause, up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2022.
Related trials for Metastatic Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingObservational study
A Non-Interventional Study PASS to Characterize Secondary Malignancies of Tcell Origin Following Tisagenlecleucel Therapy
Secondary Malignancies of T-cell Origin
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.
Zev Wainberg principal investigator
Jonsson Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PARP inhibitor BMN-673, temozolomide and irinotecan hydrochloride in people with Metastatic Cancer and Unspecified Adult Solid Tumor, run by Jonsson Comprehensive Cancer Center 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 13 inclusion and 17 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 26 Sep 2022. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Dose Limiting Toxicity graded using the NCI CTCAE v. 4.03 (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Sep 2022.