Clinical Trials /

Temozolomide, Cisplatin, and Nivolumab in People With Colorectal Cancer

NCT04457284

Description:

This study will test whether the combination of cisplatin, nivolumab, and temozolomide is an effective treatment for in people with advanced and/or metastatic colorectal cancer that is mismatch repair-proficient (MMR-proficient). The researchers will also look at how safe the study drug combination is in participants.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Temozolomide, Cisplatin, and Nivolumab in People With Colorectal Cancer
  • Official Title: A Phase II Study of Temozolomide, Cisplatin and Nivolumab in MMR-Proficient Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 20-202
  • NCT ID: NCT04457284

Conditions

  • Colorectal Adenocarcinoma

Interventions

DrugSynonymsArms
Temozolomide (TMZ)temozolomide, cisplatin and nivolumab
Cisplatintemozolomide, cisplatin and nivolumab
Nivolumabtemozolomide, cisplatin and nivolumab

Purpose

This study will test whether the combination of cisplatin, nivolumab, and temozolomide is an effective treatment for in people with advanced and/or metastatic colorectal cancer that is mismatch repair-proficient (MMR-proficient). The researchers will also look at how safe the study drug combination is in participants.

Trial Arms

NameTypeDescriptionInterventions
temozolomide, cisplatin and nivolumabExperimentalSubjects will receive oral TMZ at 150-200 mg/m2 day 1 to 5 every 4 weeks, cisplatin via IV infusion at 40 mg/m2 every two weeks (Q2W), and nivolumab via IV infusion at 480 mg every four weeks (Q4W).
  • Temozolomide (TMZ)
  • Cisplatin
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Subject or legally authorized representative is willing and able to provide written
             informed consent/assent for the trial.

          -  Histologically- or cytologically- confirmed colorectal adenocarcinoma.

          -  Locally advanced unresectable or metastatic CRC.

          -  Undergone testing for MSI/dMMR and determined to be MSS or MMR proficient.

          -  Undergone testing for BRAF and POLE and determined to be wild type.

          -  Subjects must be refractory to, or intolerant of, at least 2 lines of standard
             chemotherapy, according to NCCN guidelines for patients eligible for intensive
             therapy, or have received prior FOLFOXIRI. Patients are considered refractory if
             progressed within 3 months of last dose, or within 6 months of completing adjuvant
             FOLFOX/CAPEOX. At a minimum, such therapies should include oxaliplatin, irinotecan and
             a fluoropyrimidine.

          -  At least one index lesion which is measurable based on RECIST 1.1.

          -  Be ≥ 18 years of age on day of signing informed consent.

          -  Consent for use of archival tissue and blood draws for research purposes.

          -  Have an ECOG performance status of 0 or 1.

          -  Demonstrate adequate organ function as defined in Table 6.1, all screening labs should
             be performed within 28 days of treatment initiation.

          -  Adequate organ function, defined as:

               -  Absolute Neutrophil Count ≥ 1,500/mcL.

               -  Platelet count ≥ 100,000/mcL.

               -  Serum creatinine ≤ 1.5 x ULN or CrCl ≥60 mL/min for subjects with creatinine
                  levels >1.5 ULN.

               -  WBC ≥ 2000/μL

               -  Hemoglobin ≥ 9.0 g/dL

               -  AST and ALT ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with liver metastases.

               -  Bilirubin ≤ 1.5 × ULN or Direct bilirubin ≤ ULN for subjects with bilirubin
                  levels >1.5

               -  INR/PT and PTT ≤1.5 X ULN unless on anticoagulant therapy and PT/PTT within
                  therapeutic range.

        aCreatinine clearance should be calculated per institutional standard.

          -  Adequate method of contraception.

        Exclusion Criteria:

          -  Subject is currently participating in or has participated in a study of an
             investigational agent or using an investigational device within 4 weeks of the first
             dose of treatment.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10
             mg/day prednisone, or equivalent) or any other form of immunosuppressive therapy
             within 7 days prior to the first dose of trial treatment. Inhaled or topical steroids
             are permitted in the absence of active autoimmune disease

          -  Prior chemotherapy, targeted small molecule therapy, or biological therapy, within 2
             weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline)
             from adverse events due to a previously administered agent (exc. alopecia).

          -  If subject received major surgery, they must have recovered adequately prior to
             starting therapy.

          -  Has a known additional malignancy that is progressing or requires active treatment.

          -  Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment.

          -  Has an active, known or suspected autoimmune disease requiring systemic treatment
             within the past 3 months or a documented history of clinically severe autoimmune
             disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
             Subjects with vitiligo or resolved childhood asthma/atopy, type 1 diabetes mellitus
             are permitted. Subjects that require intermittent use of bronchodilators or local
             steroid injections would not be excluded from the study. Subjects with hypothyroidism
             stable on hormone replacement or Sjogren's syndrome will not be excluded from the
             study.

          -  Has an active infection requiring systemic therapy

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or it is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 5 months for females, 7 months for males after the last dose of trial
             treatment.

          -  Prior anti-PD-1, anti-PDL-1, anti-PDL-2, anti-Cytotoxic T-lymphocyte-associated
             antigen-4 (CTLA-4) antibody or any other antibody or drug specifically targeting
             T-cell co-stimulation or checkpoint pathways.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment.

          -  Subject is a prisoners, or compulsory detained
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response
Time Frame:1 year
Safety Issue:
Description:will be evaluated in this study using the new international criteria proposed in RECIST 1.1 [Eur J Ca 45:228-247, 2009]. Changes in the largest diameter (unidimensional measurement) of the tumor and the shortest diameter of malignant lymph nodes are used with the RECIST criteria.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Temozolomide
  • Cisplatin,
  • Nivolumab
  • 20-202

Last Updated

June 30, 2020