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Metastatic Colorectal CancerPhase 1/2379NCT03791398

BrUOG 379 Phase Ib/II Trial ONC201 + Nivolumab in MSS mCRC

A Phase 1/2 study testing Dose level 1 ONC201 625mg, Dose level 2 ONC201 500mg and Dose level 3 ONC201 375mg in people with Metastatic Colorectal Cancer, run by Brown University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a single arm Phase Ib/II, open label, safety, pharmacokinetic, pharmacodynamics and efficacy study of ONC201 in combination with Opdivo (Nivolumab) in adult patients with metastatic colorectal cancer, for whom no standard therapy is available. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Dose level 1 ONC201 625mg, Dose level 2 ONC201 500mg and Dose level 3 ONC201 375mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
15 Nov 2019to 5 Aug 2021
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have a histologically/cytologically -confirmed primary colorectal tumor, with confirmation of being microsatellite stable.
  • Radiographic or clinical evidence of metastatic disease that has progressed after at least 2 prior regimens. Prior bevacizumab, cetuximab, trifluridine and tipiracil , or regorafenib is allowed, prior FOLFIRI and FOLFOX treatment is required. (Treatment with a FOLFIRINOX regimen will count as 2 regimens). Prior treatment does not have to have been in the metastatic setting.
  • Patients must have measurable disease by RECIST criteria
  • All patients must have a tumor(s) located in an area that that can be biopsied as confirmed by treating physician
  • All patients must submit representative tissue from their malignancy if it is confirmed there is enough tissue from prior surgery or most recent biopsy.
  • All previous therapies for cancer, including radiotherapy, major surgery and investigational therapies must be discontinued for ≥ 14 days before the first dose of ONC201
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  • All clinically significant adverse events related to any prior therapy must have resolved to Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE v5.0), except alopecia or parameters defined in this eligibility list.
  • Age ≥ 18 years.
  • ECOG performance status ≤ 2.
  • Adequate organ and marrow function as defined below:
  • Absolute neutrophil count ≥1,000/mm3 without growth factor use ≤ 7 days prior to treatment
  • Platelets ≥75,000/mm3 without platelet transfusion ≤ 7 days prior to treatment
  • Hemoglobin>8.0 mg/dL without red blood cell transfusion ≤ 7 days prior to treatment
  • Total serum bilirubin<1.5 X upper limit of normal (ULN)
  • AST (SGOT)/ALT (SGPT)≤2 X ULN; ≤ 5 X ULN if liver dysfunction is felt to be secondary to tumor burden within 14 days prior to treatment, Serum creatinine ≤ 1.5 X ULN (OR creatinine clearance ≥ 60 mL/min/1.73 m2) within 14 days prior to treatment
  • Serum or urine pregnancy test (for females of childbearing potential) negative ≤7 days of treatment
  • Ability to understand and the willingness to sign a written informed consent document and comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
  • Female patients of child-bearing potential must be practicing an effective form of contraception from the time of informed consent and for the duration of the study treatment through 5 months after the last dose of drug (ONC201 or Nivolumab, whichever is administered last). The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate.
  • Male patients must be surgically sterile (provide date of surgery) or must agree to use effective contraception from the time of informed consent and for the duration of the study treatment through 7 months after the last dose of drug (ONC201 or Nivolumab, whichever is administered last). The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate.
  • Patients must agree to the required tumor biopsies to enroll in the trial.

Who cannot join

  • Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases > 28 days prior to registration, including radiotherapy or surgery. Steroids for the treatment of brain metastasis are not permitted.
  • Patients with prior treatment with ONC201 will be excluded
  • Active inflammatory gastrointestinal disease such as severe chronic diarrhea (unless related to underlying malignancy), gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration. Gastroesophageal reflux disease under controlled treatment with proton pump inhibitors is allowed.
  • Pregnant or breast feeding.
  • Current active treatment in another clinical study (treatment trial) within 14 days of D-7.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics, hepatitis, active rheumatologic or collagen vascular disease, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. (testing is not required for eligibility).
  • Any of the following in the previous 3 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism as defined by treating physician.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study.
  • Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day 1 of treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer are excluded if there is any evidence of other malignancy being present within the last three years (2 years for invasive breast cancer). However, patients with a malignancy that is non-likely to require treatment, as per the treating physician, in the next 2 years, such as a completely resected, early stage breast cancer, or other malignancies treated with curative intent are eligible. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
  • Prior treatment with immunotherapy for any cancer, including immune checkpoint inhibitors or anti-CTLA4 agents
  • Participants who have received a live / attenuated vaccine within 30 days of first treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Lifespan Cancer Institute: The Miriam and Rhode Island Hospitals

    Providence, Rhode Island, 02903

Other trials in United States

About this study

Official title: BrUOG 379: A Phase Ib/II Single Arm Study of ONC201 Plus Nivolumab in Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC) Patients

This is a single arm Phase Ib/II, open label, safety, pharmacokinetic, pharmacodynamics and efficacy study of ONC201 in combination with Opdivo (Nivolumab) in adult patients with metastatic colorectal cancer, for whom no standard therapy is available. This study will enroll adult patients with metastatic colorectal cancer who progressed after at least two lines of therapy.

Being tested
Dose level 1 ONC201 625mg, Dose level 2 ONC201 500mg, Dose level 3 ONC201 375mg
Keywords
Metastatic, colorectal cancer, colon cancer, microsatellite stable
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis, Colonic Neoplasms

What participants receive

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

  • Dose level 1 ONC201 625mgDrug

    Also called ONC201 + Nivolumab

    ONC201 625mg + Nivolumab 240mg IV flat dose

  • Dose level 2 ONC201 500mgDrug

    Also called ONC201 + Nivolumab

    ONC201 500mg + Nivolumab 240mg IV flat dose

  • Dose level 3 ONC201 375mgDrug

    Also called ONC201 + Nivolumab

    ONC201 375mg + Nivolumab 240mg IV flat dose

Study groups in NCT03791398
Study groupRoleWhat they receive
ONC201 Level 1 (Starting Dose Level)Experimental625mg ONC201 Cycle 1 Day -7 dose then once week
Receives: Drug: Dose level 1 ONC201 625mg
ONC201 Level 2Experimental500 mg ONC201 Cycle 1 Day -7 dose then once week
Receives: Drug: Dose level 2 ONC201 500mg
ONC201 Level 3Experimental375 mg ONC201 Cycle 1 Day -7 dose then once week
Receives: Drug: Dose level 3 ONC201 375mg
NivolumabExperimental240mg IV flat dose q 2 weeks
Receives: Drug: Dose level 1 ONC201 625mg; Drug: Dose level 2 ONC201 500mg; Drug: Dose level 3 ONC201 375mg

What is being measured

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

  1. Maximum Tolerated Dose of ONC201 With Nivolumab for Phase II

    Measured: Cycle 1 (each cycle is approximately 4 weeks) through pre-dosing cycle 2, approximately 1 month

  2. Progression Free Survival

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: From start of protocol therapy until death or progression, a maximum of 6 months from end of therapy.

Timeline

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

  1. First posted2 Jan 2019
  2. Study start15 Nov 2019
  3. Primary completion16 Jun 2021
  4. Study completion5 Aug 2021

Why it stopped: Lack of efficacy

Resources

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
Non-randomised
Intervention model
Single group
Model description
This is a single arm study of de-escalating arms to determine the MTD and then expand the trial.It is not randomized.
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03791398
Sponsor's protocol ID
BrUOG 379
Acronym
379
Status last verified
Feb 2023
First submitted
26 Dec 2018
Last updated
17 Feb 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dose level 1 ONC201 625mg, Dose level 2 ONC201 500mg and Dose level 3 ONC201 375mg in people with Metastatic Colorectal Cancer, run by Brown University 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 20 inclusion and 14 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: stopped early, as of the sponsor's last update on 17 Feb 2023. 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 21 Jun 2022). 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?

Maximum Tolerated Dose of ONC201 With Nivolumab for Phase II (time frame: Cycle 1 (each cycle is approximately 4 weeks) through pre-dosing cycle 2, approximately 1 month). The study lists 2 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 NCT03791398.

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 17 Feb 2023.

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