Triple Therapy for Colorectal Cancer

Recruiting at 7 trial locations

Overseen By Neil H Segal, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active CNS metastases, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

18 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment.

What data supports the effectiveness of the drug combination of Cisplatin, Nivolumab, and Temozolomide for colorectal cancer?

Research shows that the combination of Temozolomide and Cisplatin has been effective in treating other cancers, like melanoma and glioma, by enhancing the antitumor activity. This suggests potential effectiveness for colorectal cancer, although direct evidence for this specific cancer is not provided. ^{1 2 3 4 5}

Is the triple therapy for colorectal cancer, including Cisplatin, Nivolumab, and Temozolomide, generally safe for humans?

Cisplatin has been used in cancer treatments and is known to cause nausea and vomiting, but these side effects can be managed with medications like metoclopramide. The safety of Cisplatin in humans is established, but specific safety data for the combination with Nivolumab and Temozolomide is not provided in the available research. ^{6 7 8 9 10}

What makes the triple therapy for colorectal cancer unique?

The triple therapy for colorectal cancer combines Cisplatin, Nivolumab, and Temozolomide, which is unique because it includes Nivolumab, an immunotherapy drug that helps the immune system attack cancer cells, alongside traditional chemotherapy agents. This combination aims to enhance the overall effectiveness by using different mechanisms to target cancer. ^{11 12 13 14 15}

Research Team

Neil H Segal,, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with advanced colorectal cancer that's spread and hasn't responded to at least two standard chemotherapies can join this trial. They need a certain level of blood cells, good organ function, and no major health issues like HIV or active infections. Pregnant or breastfeeding individuals are excluded.

Inclusion Criteria

I am fully active or can carry out light work.

aCreatinine clearance should be calculated per institutional standard.

My recent tests show my organs are functioning well.

Exclusion Criteria

I have another cancer, but it's either not growing or doesn't need treatment, except for certain skin cancers or treated cervical cancer.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral temozolomide at 150-200 mg/m2 day 1 to 5 every 4 weeks, cisplatin via IV infusion at 40 mg/m2 every two weeks, and nivolumab via IV infusion at 480 mg every four weeks

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cisplatin
• Nivolumab
• Temozolomide

Trial Overview The study is testing a combination of three drugs: Temozolomide (TMZ), Cisplatin, and Nivolumab in people whose colorectal cancer has not been helped by standard treatments. It aims to see if this mix is safe and works better for those with specific genetic features in their tumors.

Participant Groups

Group I: temozolomide, cisplatin and nivolumab Experimental Treatment 3 Interventions

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).

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

In a phase II trial involving 33 patients with recurrent malignant glioma, the combination of cisplatin and temozolomide showed a progression-free survival (PFS) rate of 52% at 6 months, indicating a potential benefit for patients with this aggressive cancer.

The treatment resulted in partial responses in 18.8% of patients and stable disease in 39.9%, but also led to significant toxic effects, including severe neutropenia and thrombocytopenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin plus temozolomide, in recurrent and progressive malignant glioma patients. Silvani, A., Eoli, M., Salmaggi, A., et al.[2022]

In a study of 32 patients with brain metastases from solid tumors, the combination of temozolomide (TMZ) and cisplatin (CDDP) showed promising efficacy, with a 28.1% partial response rate and a median overall survival of 5.5 months.

The treatment was generally well-tolerated, although some patients experienced grade III-IV toxicities, including anemia and leukopenia, indicating that while the regimen is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study. Christodoulou, C., Bafaloukos, D., Linardou, H., et al.[2018]

The modified DCS therapy (docetaxel, cisplatin, and S-1) demonstrated a high overall response rate of 79.1% in patients with unresectable gastric cancer, with 34.9% of patients eligible for curative conversion surgery.

While modified DCS resulted in fewer severe toxicities compared to the original regimen, significant side effects like grade 3/4 neutropenia (79.1%) and febrile neutropenia (34.9%) were still common, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of modified docetaxel, cisplatin, and S-1 (mDCS) chemotherapy for unresectable advanced gastric cancer. Uemura, N., Kikuchi, S., Sato, Y., et al.[2022]

The study evaluated the safety of a triple combination therapy of Paclitaxel (PTX), Cisplatin (CDDP), and 5-fluorouracil (5-FU) in 12 patients with unresectable or recurrent gastric cancer, finding it to be a safe treatment option despite some cases of hematological and non-hematological toxicities.

While there were instances of grade 3 or higher toxicities, including leukopenia and neutropenia, no infections occurred, and the maximum tolerated dose of 5-FU was determined to be 400 mg, indicating that the combination therapy can be administered with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel, cisplatin and 5-fluorouracil combination chemotherapy for unresectable / recurrent gastric cancer. Kato, J., Nagahara, A., Iijima, K., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Temozolomide and cisplatin versus temozolomide in patients with advanced melanoma: a randomized phase II study of the Hellenic Cooperative Oncology Group. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. [2019]

3. Greece pubmed.ncbi.nlm.nih.gov

Temozolomide and cisplatin in avdanced malignant melanoma. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin plus temozolomide, in recurrent and progressive malignant glioma patients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Metoclopramide. A review of antiemetic trials. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Intravenous metoclopramide. An effective antiemetic in cancer chemotherapy. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Comparison of methylprednisolone and metoclopramide in the prophylactic treatment of cis-platin-induced nausea and vomiting. [2022]

9. England pubmed.ncbi.nlm.nih.gov

5-Hydroxytryptamine M-receptor antagonism to prevent cisplatin-induced emesis. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Chlorpromazine, placebo and droperidol in the treatment of nausea and vomiting associated with cisplatin therapy. [2019]

11. Japan pubmed.ncbi.nlm.nih.gov

Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer. [2018]

12. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of modified docetaxel, cisplatin, and S-1 (mDCS) chemotherapy for unresectable advanced gastric cancer. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel, cisplatin and 5-fluorouracil combination chemotherapy for unresectable / recurrent gastric cancer. [2015]

14. Japan pubmed.ncbi.nlm.nih.gov

Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer. [2019]

15. England pubmed.ncbi.nlm.nih.gov

Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. [2021]