Clinical Trials /

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

NCT03791398

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: BrUOG 379
  • NCT ID: NCT03791398

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
Dose level 1 ONC201 625mgONC201 + NivolumabONC201 Level 1
Dose level 2 ONC201 500mgONC201 + NivolumabONC201 Level 2
Dose level 3 ONC201 375mgONC201 + NivolumabONC201 Level 3
Dose level 4 ONC201 250mgONC201+ NivolumabONC201 Level 4
Dose level 5 ONC201 125mgONC201+NivolumabONC201 Level 5

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ONC201 Level 1Experimental625mg ONC201 Cycle 1 Day -7 dose then once week
  • Dose level 1 ONC201 625mg
ONC201 Level 2Experimental500 mg ONC201 Cycle 1 Day -7 dose then once week
  • Dose level 2 ONC201 500mg
ONC201 Level 3Experimental375 mg ONC201 Cycle 1 Day -7 dose then once week
  • Dose level 3 ONC201 375mg
ONC201 Level 4Experimental250mg ONC201 Cycle 1 Day -7 dose then once week
  • Dose level 4 ONC201 250mg
ONC201 Level 5Experimental125 mg ONC201 Cycle 1 Day -7 dose then once week
  • Dose level 5 ONC201 125mg
NivolumabExperimental240mg IV flat dose q 2 weeks
  • Dose level 1 ONC201 625mg
  • Dose level 2 ONC201 500mg
  • Dose level 3 ONC201 375mg
  • Dose level 4 ONC201 250mg
  • Dose level 5 ONC201 125mg

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must have a histologically/cytologically -confirmed primary colorectal tumor,
             with confirmation of being microsatellite stable.

          2. Radiographic or clinical evidence of metastatic disease that has progressed after at
             least 2 prior regimens.

          3. Patients must have measurable disease by RECIST criteria

          4. All patients must have a tumor(s) located in an area that that can be biopsied as
             confirmed by treating physician

          5. All patients must submit representative tissue from their malignancy if it is
             confirmed there is enough tissue from prior surgery or most recent biopsy.

          6. All previous therapies for cancer, including radiotherapy, major surgery and
             investigational therapies must be discontinued for ≥ 14 days before the first dose of
             ONC201

          7. 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.

          8. Age ≥ 18 years.

          9. ECOG performance status ≤ 2.

         10. Adequate organ and marrow function as defined below:

               1. Absolute neutrophil count ≥1,000/mm3 without growth factor use ≤ 7 days prior to
                  treatment

               2. Platelets ≥75,000/mm3 without platelet transfusion ≤ 7 days prior to treatment

               3. Hemoglobin>8.0 mg/dL without red blood cell transfusion ≤ 7 days prior to
                  treatment

               4. Total serum bilirubin<1.5 X upper limit of normal (ULN)

               5. 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

               6. Serum or urine pregnancy test (for females of childbearing potential) negative ≤7
                  days of treatment

         11. 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.

         12. Female patients of child-bearing potential must be practicing an effective form of
             contraception during study treatment and for 90 days 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.

         13. Male patients must be surgically sterile (provide date of surgery) or must agree to
             use effective contraception during the period of the trial and for at least 90 days
             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.

         14. Patients must agree to the required tumor biopsies to enroll in the trial.

        Exclusion Criteria:

          1. 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.

          2. Patients with prior treatment with ONC201 will be excluded

          3. 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.

          4. Pregnant or breast feeding.

          5. Current active treatment in another clinical study (treatment trial) within 14 days of
             D-7.

          6. 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.

          7. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness. (testing is not required for eligibility).

          8. 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.

          9. 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.

         10. 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.

         11. 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

         12. 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.

         13. Prior treatment with immunotherapy for any cancer, including immune checkpoint
             inhibitors or anti-CTLA4 agents
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose and/or recommended 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
Safety Issue:
Description:Dose limiting toxicities defined per protocol

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Khaldoun Almhanna

Trial Keywords

  • Metastatic
  • colorectal cancer
  • colon cancer
  • microsatellite stable

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