Nivolumab and Ipilimumab and Radiation Therapy in MSS and MSI High Colorectal and Pancreatic Cancer

NCT03104439 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 17-021
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a combination of drugs with radiation therapy as a possible treatment for Microsatellite Stable Colorectal Cancer, Pancreatic Cancer, or MSI High Colorectal Cancer. The interventions involved in this study are:

• Nivolumab
• Ipilimumab
• Radiation Therapy

Conditions

Microsatellite Stable Colorectal Cancer; Pancreatic Cancer; MSI High Colorectal Cancer

Keywords

Pancreatic Cancer; Microsatellite Stable Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate

  The percentage of participants with disease control following treatment with nivolumab/ipilimumab/radiation. Disease control is defined as the percentage of participants who have achieved complete response (CR), partial response (PR), or stable disease (SD) as defined by Response Evaluation Criteria In Solid Tumors (RECIST). Tumors may be evaluated for response with X-ray, computerized tomography (CT) scan, Magnetic resonance imaging (MRI), FDG (fluorodeoxyglucose) positron emission tomography (PET) scan, PET-CT, or cytology/histology.

  2 years

Secondary Outcomes (2)

• Median Progression free Survival

  2 years

• Median Overall Survival

  2 years

Study Arms (1)

Nivolumab+Ipilimumab

EXPERIMENTAL

* Nivolumab will be administered intravenously 3 times per cycle * Ipilimumab will be administered intravenously once per cycle * Radiation Therapy will be administered per hospital standard

Drug: Nivolumab; Drug: Ipilimumab; Radiation: Radiation Therapy

Interventions

Nivolumab DRUG

The antibodies in nivolumab work by causing programmed cell death of the cancer cells

Also known as: Opdivo

Nivolumab+Ipilimumab

Ipilimumab DRUG

The antibodies in ipilimumab work by not allowing cancer cell growth

Also known as: Yervoy

Nivolumab+Ipilimumab

Radiation Therapy RADIATION

Radiation therapy is believed to increase the likelihood of response of immunotherapy

Nivolumab+Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed adenocarcinoma of colorectal or pancreatic origin
• Age \>18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Life expectancy of greater than 3 months
• Participants must have normal organ and marrow function as defined in Table 1, all screening labs should be performed within 14 days of protocol registration.
• Table 1 Adequate Organ Function Laboratory Values
• System Laboratory Value
• Hematological
• Absolute neutrophil count (ANC) ≥1500 /mcL
• White blood count (WBC) ≥2000 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL
• Renal
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
• Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL

You may not qualify if:

• Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days of protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Participants who are receiving any other investigational agents.
• Patients are excluded if they have an active, known or suspected autoimmune disease other than those listed below. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Colorectal patients are excluded if they have had prior systemic treatment with an anti-CTLA4, anti-PD1 (Programmed cell death protein 1) or PDL1 (Programmed death-ligand 1) antibody. Pancreatic patients are excluded if they have previously received anti-CTLA-4 therapy. Prior PD-1 or PDL1 therapy will be permitted for pancreas patients
• Has a known history of active TB (Bacillus Tuberculosis)
• Patients are excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Patients are excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). These participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• 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 woman and 7 months for men, after the last dose of trial treatment.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Parikh AR, Szabolcs A, Allen JN, Clark JW, Wo JY, Raabe M, Thel H, Hoyos D, Mehta A, Arshad S, Lieb DJ, Drapek LC, Blaszkowsky LS, Giantonio BJ, Weekes CD, Zhu AX, Goyal L, Nipp RD, Dubois JS, Van Seventer EE, Foreman BE, Matlack LE, Ly L, Meurer JA, Hacohen N, Ryan DP, Yeap BY, Corcoran RB, Greenbaum BD, Ting DT, Hong TS. Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial. Nat Cancer. 2021 Nov;2(11):1124-1135. doi: 10.1038/s43018-021-00269-7. Epub 2021 Nov 18.

  PMID: 35122060 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Nivolumab; Ipilimumab; Radiotherapy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Julie Koenig, MD

  Massachusetts General Hospital

  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: PRINCIPAL INVESTIGATOR
• PI Title: Physician, Radiation Oncology

Study Record Dates

• First Submitted: April 3, 2017
• First Posted: April 7, 2017
• Study Start: May 10, 2017
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)