A Phase II Study Evaluating an Organ Preservation Strategy Using Immune Checkpoint Blockade for Participants With Primary Colorectal or Gastroesophageal Cancer

NCT06410534 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 10001691001691-C
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: People with colorectal cancer (CRC) or gastroesophageal cancer (GEC) must often have major surgery to remove tumors from the esophagus, stomach, colon, or rectum. These surgeries can have adverse effects on their quality of life. Researchers want to know if one or two approved drugs (nivolumab with or without ipilimumab) can help people with CRC or GEC delay or avoid surgery. Objective: To test 1 or 2 drugs in people with CRC or GEC. Eligibility: People aged 18 years and older with CRC or GEC. People with GEC must also have changes in a particular gene. Design: Participants will visit the clinic about 15 times over the first 2 years. Each visit will last 4 to 8 hours. Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans. Small samples of tissue will be collected from their upper or lower digestive tract where the tumor is located. Both ipilimumab and nivolumab are administered through a tube attached to a needle inserted into a vein in the arm. Some participants will receive both drugs. Some will receive only nivolumab. Treatment will be given once every 3 weeks for up to 8 cycles up to (24 weeks). Participants will be evaluated every 6 weeks. Those who are responding well will continue with the drug treatments. If their disease progresses, they will go to surgery. After treatment ends, participants will have follow-up visits every 6 months for up to 5 years....

Conditions

Colorectal Cancer; Gastroesophageal Cancer

Keywords

nivolumab; Ipilimumab; Immune Checkpoint Blockade; mismatch repair

Outcome Measures

Primary Outcomes (1)

• Clinical complete response (CR) or near-complete response (nCR)

  Assessed endoscopically with concordant radiographic findings clinical CR/nCR in each cohort will be reported along with 80% and 95% two-sided confidence intervals.

  6, 12 18 and 24 weeks

Secondary Outcomes (5)

• Disease free survival (DFS)

  6, 12 18 and 24 weeks then every 4 months for 2 years then every 6 months for years 3-5

• Resection-free survival (RFS)

  6, 12 18 and 24 weeks then every 4 months for 2 years then every 6 months for years 3-5

• Safety

  until 30 days after the last dose of study drugs

• Delay in surgery

  until 30 days after documented progressive disease

• Locoregional failure

  6, 12 18 and 24 weeks then every 4 months for 2 years then every 6 months for years 3-5

Study Arms (2)

1: nivolumab and ipilimumab

EXPERIMENTAL

Nivolumab (3 mg/kg) every 3 weeks for up to an initial 4 cycles (an additional 4 cycles may be given depending on response, for a total of 8 cycles); low-dose ipilimumab at 1 mg/kg every other cycle (every 6 weeks) for up to an initial 2 doses (an additional 2 doses may be given depending on response, for a maximum of 4 doses).

Drug: nivolumab; Drug: ipilimumab

2: nivolumab

EXPERIMENTAL

Nivolumab (3 mg/kg) every 3 weeks for up to an initial 4 cycles (an additional 4 cycles may be given depending on response, for a total of 8 cycles).

Drug: nivolumab

Interventions

nivolumab DRUG

Nivolumab will be dosed at 3 mg/kg and given as an IV over 30-60 minutes on day 1 of each cycle. It will be administered every 3 weeks (21 days) for up to 8 cycles

1: nivolumab and ipilimumab; 2: nivolumab

ipilimumab DRUG

Ipilimumab will be dosed at 1 mg/kg and given as an IV over approximately 30 minutes on day 1 of every other cycle (every 6 weeks or 42 days) for up to 4 doses

1: nivolumab and ipilimumab

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have biopsy-proven stage I-III colorectal cancer (CRC) \[any MMR or Tumor Mutational Burden (TMB) status\] or stage I-III gastroesophageal cancer (GEC) (MMR deficient only).
• Participants with known mismatch repair protein expression by immunohistochemical staining and/ or known next-generation sequencing report of tumor mutational burden and/or microsatellite status. Note: For participants that come to NIH with an equivocal MMR status, next-generation sequencing (NGS) by TSO500 will be done at NIH.
• More than four weeks must have elapsed since completion of any prior systemic therapy or radiotherapy at the time of enrollment. Participants are permitted to have undergone prior treatment with systemic chemotherapy (e.g. FOLFOX, FOLFIRI, FLOT) and/or radiotherapy. Note: Participant may have undergone minor surgical procedures within the four weeks prior to enrollment, if related major organ toxicities have recovered to \<= grade 1.
• Participants must have endoscopically evaluable disease.
• Age \>=18 years.
• ECOG performance status =\<1.
• Participants must have adequate organ and marrow function as defined below:
• White Blood Cell (WBC), \>=3,000/mm\^3
• Hemoglobin \>8.0 d/dL, (transfusion permitted)
• platelets, \>=100,000/mm\^3
• total bilirubin, \< 1.5 mg/dL (except in participants with Gilbert s Syndrome, who must have a total bilirubin \< 3.0 mg/dL)
• AST(SGOT)/ALT(SGPT), 5.0 X institutional upper limit of normal
• serum creatinine, \< 1.6 mg/dL
• No pre-existing autoimmune or infectious conditions for which treatment with immune checkpoint blockade is contraindicated.
• Serology

You may not qualify if:

• Participants who are receiving any other investigational agents.
• Previous treatment with checkpoint inhibitors (anti-CTLA-4, anti-PD-1 or anti-PD-L1 antibodies) for the primary tumor in question.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab and ipilimumab or other agents used in study.
• Concomitant medications, such as steroids or other immunosuppressive agents, that have the potential to affect the activity of the study agents.
• Any active or uncompensated major medical illness that would preclude major intraabdominal surgery.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) or any immune disorder that would be a contraindication to ICB treatment.
• Concurrent opportunistic infections
• Tumor is causing symptomatic bowel obstruction (participants with a diverting ostomy are eligible).
• History of significant autoimmune adverse events due to administration of anti-PD-1, anti-PD L1 or anti-CTLA-4 antibodies when given for prior indication.
• Participants who are medically unfit to undergo major abdominal surgery.
• Participants with tumors that are unable to be endoscopically evaluated.
• Uncontrolled intercurrent illness that would limit compliance with study requirements.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nicholas D Klemen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2024
• First Posted: May 13, 2024
• Study Start: September 9, 2025
• Primary Completion: September 9, 2025
• Study Completion: September 9, 2025
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)