Temozolomide, Cisplatin, and Nivolumab in People With Colorectal Cancer

NCT04457284 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-202
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Colorectal Adenocarcinoma

Keywords

Temozolomide; Cisplatin,; Nivolumab; 20-202

Outcome Measures

Primary Outcomes (1)

• Response

  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.

  1 year

Study Arms (1)

temozolomide, cisplatin and nivolumab

EXPERIMENTAL

Subjects 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).

Drug: Temozolomide (TMZ); Drug: Cisplatin; Drug: Nivolumab

Interventions

Temozolomide (TMZ) DRUG

TMZ 150 mg/m2 Day 1 - 5 Q4W PO Cycle 1 TMZ 200 mg/m2 Day 1 - 5 Q4W PO Cycle 2 +

temozolomide, cisplatin and nivolumab

Cisplatin DRUG

Cisplatin 40 mg/m2 Q2W IV infusion Cycle 1 +

temozolomide, cisplatin and nivolumab

Nivolumab DRUG

Nivolumab 480 mg Q4W IV infusion Cycle 1 +

temozolomide, cisplatin and nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Rockville Centre, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

Temozolomide; Cisplatin; Nivolumab

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Neil Segal, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a two-stage design, single arm, phase II study.

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: July 7, 2020
• Study Start: November 18, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)