Solid TumorsPhase 1NCT02250781
Oral ONC201 in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing Oral ONC201 in people with Solid Tumors, run by Rutgers, The State University of New Jersey at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of Oral ONC201 in treating patients with advanced solid tumors. Oral ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Oral ONC201
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jan 2015to 25 Oct 2018
- 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
- Patients with an advanced solid tumor that is refractory to standard treatment, or for which no standard therapy is available, or the subject refuses standard therapy
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- All patients must have measurable or evaluable disease defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria; if the patient has received prior radiation therapy one measurable lesion must be outside the irradiated field; lesions within an irradiated field will be followed as non-target lesions and considered evaluable; if the only site of measurable disease is within a previously irradiated field then 6 months must have elapsed between the completion of radiation therapy and entry on study to be considered measurable
- Patients are eligible for enrollment if they have not had prior investigational or approved cytotoxic chemotherapy within 28 days prior to the first dose (week 1, day 1); 42 days in the case of alkylating agents; 28 days or 5 half-lives (whichever is less; but not less than 14 days) in case of investigational or approved molecularly targeted agent; 14 days in the case of radiotherapy; any number of prior therapies is allowable
- All adverse events grade =< 2 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved, except for alopecia or neuropathy; patients are eligible for enrollment if they have had no surgery in the prior 6 weeks (minor surgical procedures such as skin biopsies and port placement done on an outpatient basis do not require a waiting period)
- Absolute neutrophil count >= 1,500/mcL
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- Platelets >= 100,000/mcL
- Hemoglobin >= 9.0 mg/dL without transfusion in 2 prior weeks
- Total bilirubin within normal range; for patients with liver metastases, serum bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate transaminase [SGPT]) =< 2.5 x upper limit of normal
- Measured OR estimated creatinine clearance >= 40 mL/min/1.73 m^2 for patients with creatinine levels above normal
- Men or women treated or enrolled on this protocol must agree to use double barrier contraceptives; oral, implantable, or injectable contraceptives are not considered effective for this study; women of child-bearing potential must have a negative serum pregnancy test =< 72 hours prior to initiating treatment; subjects must agree to use double barrier contraceptive therapy for the duration of study participation, and 4 months after completion of ONC201 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Tumor specimen (paraffin-embedded block or frozen tissue) from prior resection or biopsy available that is sufficient to perform pharmacodynamic assays (>= 3 slides for immunohistochemistry [IHC]) - mandatory for patients in the dose expansion cohort only
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients with symptomatic brain metastases are excluded; however, patients with asymptomatic central nervous system (CNS) metastases may participate in this trial; the patient must have completed any prior local treatment for CNS metastases > 28 days prior to study entry including radiotherapy or surgery; patients receiving steroids for CNS metastases may not participate on this study
- Prior bevacizumab for treatment of glioblastoma or high grade glioma
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
- Patients with a known human immunodeficiency virus (HIV)-positive test on combination antiretroviral therapy are ineligible for the initial first-in-man trial
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- Patient has active cardiac disease including any of the following:
- Corrected QT (QTc) > 500 msec on screening electrocardiogram (ECG) (using the QTc Fridericia [F] formula)
- Angina pectoris that requires the use of anti-anginal medication
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
- Conduction abnormality requiring a pacemaker
- Valvular disease with document compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function
- History of documented congestive heart failure (New York Heart Association functional classification III-IV)
- Documented cardiomyopathy
- Patient with stroke in the last 3 months
- Patients with a history of seizures with in the past 3 months
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ONC201 (uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]) =< 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
- Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives are not considered effective for this study
- Women of child-bearing potential must have a negative serum pregnancy test =< 72 hours prior to initiating treatment
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during treatment and for 16 additional weeks after stopping treatment; the highly effective contraception is defined as either:
- True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
- Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient
- Use of a combination of any two of the following (a+b):
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
- Oral contraception, injected or implanted hormonal methods are not allowed
- Fertile males, defined as all males physiologically capable of conceiving offspring must use condom during treatment and for an additional 16 weeks after stopping treatment
- Female partner of male study subject should use highly effective contraception during dosing of any study agent and for 16 weeks after final dose of study therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
About this study
Official title: A First-in-Human Phase I Single-Agent Open-Label Dose-Escalation Study of Every Three-Week Dosing of Oral ONC201 in Patients With Advanced Solid Tumors
This phase I trial studies the side effects and best dose of Oral ONC201 in treating patients with advanced solid tumors. Oral ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the recommended phase II dose of single agent ONC201 orally once every three weeks.
SECONDARY OBJECTIVES:
- To characterize pharmacokinetics of ONC201. II. To assess serum biomarkers of therapeutic response to ONC201. III. To assess preliminary antitumor activity of ONC201 as a single agent in advanced solid tumors.
OUTLINE: This is a dose-escalation study.
Patients receive ONC201 orally (PO) on day 1. Courses repeat every 21 days for a total of 2 courses.
After completion of study treatment, patients are followed up for 4 weeks.
- Conditions
- Solid Tumors
- Being tested
- Oral ONC201
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral ONC201Drug
Also called ONC201, TIC10
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Oral ONC201) | Experimental | Patients receive Oral ONC201 PO on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Oral ONC201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity rate during cycle 1 of treatment with oral ONC201
Measured: Day 21
Secondary outcomes (6)
Recommended phase II dose (RP2D) for oral ONC201
Measured: At the end of 6 weeks therapy
Frequency of toxicities associated with ONC201
Measured: Up to 4 weeks after end of study treatment
Pharmacokinetics of oral ONC201 - Half-life
Measured: Up to 4 weeks of therapy
Pharmacokinetics of oral ONC201 - Maximum concentration
Measured: Up to 4 weeks of therapy
Pharmacokinetics of oral ONC201 - Area under the curve (AUC) over time
Measured: Up to 4 weeks of therapy
Response rate of oral ONC201 in patients with advanced solid tumors
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2014 (estimated)
- Study start12 Jan 2015
- Primary completion18 Oct 2018
- Study completion25 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Rutgers, The State University of New JerseyThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rutgers, The State University of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Responsible party
- Sponsor
- Investigators
- Jyoti Malhotra, Principal investigator, Rutgers Cancer Institute of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02250781
- Sponsor's protocol ID
- 051403
- Other IDs
- NCI-2014-01305, 051403, P30CA072720
- Status last verified
- May 2019
- First submitted
- 28 Jul 2014
- Last updated
- 22 May 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Stein MN, Malhotra J, Tarapore RS, Malhotra U, Silk AW, Chan N, Rodriguez L, Aisner J, Aiken RD, Mayer T, Haffty BG, Newman JH, Aspromonte SM, Bommareddy PK, Estupinian R, Chesson CB, Sadimin ET, Li S, Medina DJ, Saunders T, Frankel M, Kareddula A, Damare S, Wesolowsky E, Gabel C, El-Deiry WS, Prabhu VV, Allen JE, Stogniew M, Oster W, Bertino JR, Libutti SK, Mehnert JM, Zloza A. Safety and enhanced immunostimulatory activity of the DRD2 antagonist ONC201 in advanced solid tumor patients with weekly oral administration. J Immunother Cancer. 2019 May 22;7(1):136. doi: 10.1186/s40425-019-0599-8.
PubMed 31118108
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-in-Human Phase I Single-Agent Open-Label Dose-Escalation Study of Every Three-Week Dosing of Oral ONC201 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02250781
- Acronym / sponsor ID
- 051403
- Conditions
- Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Rutgers, The State University of New JerseyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
- Study start
- 12 Jan 2015 (actual)
- Primary completion
- 18 Oct 2018 (actual)
- Study completion
- 25 Oct 2018 (actual)
- First posted
- 26 Sep 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 best dose of Oral ONC201 in treating patients with advanced solid tumors. Oral ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the recommended phase II dose of single agent ONC201 orally once every three weeks.
SECONDARY OBJECTIVES:
- To characterize pharmacokinetics of ONC201. II. To assess serum biomarkers of therapeutic response to ONC201. III. To assess preliminary antitumor activity of ONC201 as a single agent in advanced solid tumors.
OUTLINE: This is a dose-escalation study.
Patients receive ONC201 orally (PO) on day 1. Courses repeat every 21 days for a total of 2 courses.
After completion of study treatment, patients are followed up for 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Oral ONC201) | Experimental | Drug: Oral ONC201Patients receive Oral ONC201 PO on day 1. Courses repeat every 21 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 (14 listed)
- Patients with an advanced solid tumor that is refractory to standard treatment, or for which no standard therapy is available, or the subject refuses standard therapy
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- All patients must have measurable or evaluable disease defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria; if the patient has received prior radiation therapy one measurable lesion must be outside the irradiated field; lesions within an irradiated field will be followed as non-target lesions and considered evaluable; if the only site of measurable disease is within a previously irradiated field then 6 months must have elapsed between the completion of radiation therapy and entry on study to be considered measurable
- Patients are eligible for enrollment if they have not had prior investigational or approved cytotoxic chemotherapy within 28 days prior to the first dose (week 1, day 1); 42 days in the case of alkylating agents; 28 days or 5 half-lives (whichever is less; but not less than 14 days) in case of investigational or approved molecularly targeted agent; 14 days in the case of radiotherapy; any number of prior therapies is allowable
- All adverse events grade =< 2 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved, except for alopecia or neuropathy; patients are eligible for enrollment if they have had no surgery in the prior 6 weeks (minor surgical procedures such as skin biopsies and port placement done on an outpatient basis do not require a waiting period)
Key exclusion criteria (34 listed)
- Patients with symptomatic brain metastases are excluded; however, patients with asymptomatic central nervous system (CNS) metastases may participate in this trial; the patient must have completed any prior local treatment for CNS metastases > 28 days prior to study entry including radiotherapy or surgery; patients receiving steroids for CNS metastases may not participate on this study
- Prior bevacizumab for treatment of glioblastoma or high grade glioma
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
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 |
|---|---|---|
| Oral ONC201Also: ONC201, TIC10Given PO | Drug | Treatment (Oral ONC201) |
Primary outcome
Dose limiting toxicity rate during cycle 1 of treatment with oral ONC201
Time frame: Day 21
6 secondary outcomes
Recommended phase II dose (RP2D) for oral ONC201
Time frame: At the end of 6 weeks therapy
Frequency of toxicities associated with ONC201
Time frame: Up to 4 weeks after end of study treatment
Pharmacokinetics of oral ONC201 - Half-life
Time frame: Up to 4 weeks of therapy
Pharmacokinetics of oral ONC201 - Maximum concentration
Time frame: Up to 4 weeks of therapy
Pharmacokinetics of oral ONC201 - Area under the curve (AUC) over time
Time frame: Up to 4 weeks of therapy
Response rate of oral ONC201 in patients with advanced solid tumors
Time frame: 3 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 22 May 2019.
- Derived from this study: PubMed 31118108Stein MN, Malhotra J, Tarapore RS, Malhotra U, Silk AW, Chan N, Rodriguez L, Aisner J, Aiken RD, Mayer T, Haffty BG, Newman JH, Aspromonte SM, Bommareddy PK, Estupinian R, Chesson CB, Sadimin ET, Li S, Medina DJ, Saunders T, Frankel M, Kareddula A, Damare S, Wesolowsky E, Gabel C, El-Deiry WS, Prabhu VV, Allen JE, Stogniew M, Oster W, Bertino JR, Libutti SK, Mehnert JM, Zloza A. Safety and enhanced immunostimulatory activity of the DRD2 antagonist ONC201 in advanced solid tumor patients with weekly oral administration. J Immunother Cancer. 2019 May 22;7(1):136. doi: 10.1186/s40425-019-0599-8.
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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.
Jyoti Malhotra principal investigator
Rutgers Cancer Institute of New Jersey
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 Oral ONC201 in people with Solid Tumors, run by Rutgers, The State University of New Jersey 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 14 inclusion and 34 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 22 May 2019. 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 rate during cycle 1 of treatment with oral ONC201 (time frame: Day 21). 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 NCT02250781, which also lists 1 linked publication.
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 22 May 2019.