Nivolumab+Ipilimumab+RT in MSS mCRC

NCT04575922 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: 20-256
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

This research is being done to study the effects of the combination of ipilimumab, nivolumab, and radiation therapy in people with metastatic microsatellite stable colorectal cancer. This research study involves the following drugs and interventions:

• Ipilimumab
• Nivolumab
• Radiation Therapy

Conditions

Metastatic Microsatellite Stable Colorectal Cancer

Keywords

metastatic microsatellite stable colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate for unirradiated lesions (ORR)

  Estimate the overall response rate (ORR) for unirradiated lesions for nivolumab/ipilimumab/radiation in metastatic, microsatellite stable colorectal cancer by RECIST 1.1. ORR is the number of patients that achieve either a CR or PR. * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From the start of the treatment until disease progression/recurrence, up to 5 years

Secondary Outcomes (5)

• Disease control rate (DCR)

  From the start of the treatment until the criteria for progression are met, up to 5 years

• Overall response rate for irradiated lesions (ORR)

  From the start of the treatment until disease progression/recurrence, up to 5 years

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE 5

  6 Weeks

• Progression-free survival (PFS)

  Duration from the first day of protocol treatment to the earliest date of tumor progression by RECIST or clinical criteria, appearance of new metastases, or death due to any cause, up to 5 years

• Overall survival (OS)

  Duration from the first day of protocol treatment to the date of death due to any cause, up to 5 years

Study Arms (1)

Nivolumab+Ipilimumab+Radiation Therapy (RT)

EXPERIMENTAL

Study cycles are 6 weeks long, participants will receive: Cycle 1: Nivolumab every 2 weeks during cycle, Ipilimumab 1x on Day 1 of cycle, and Radiation Therapy every other weekday or 2 days for a total of 3 treatments during week 1 of Cycle 1 only. Cycles 2-4: Nivolumab every 2 weeks during each cycle, Ipilimumab 1x on Day 1 of each cycle Cycles 5-Disease Progression: Nivolumab every 2 weeks during each cycle

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

Interventions

Nivolumab DRUG

Administered into vein by intravenous infusion every 2 weeks over 6 week study cycle.

Also known as: Opdivo

Nivolumab+Ipilimumab+Radiation Therapy (RT)

Ipilimumab DRUG

Administered into vein by intravenous infusion day 1 of each 6 week study cycle.

Also known as: Yervoy

Nivolumab+Ipilimumab+Radiation Therapy (RT)

Radiation Therapy RADIATION

3 radiation treatments, every other weekday or 2 days during week 1 of cycle 1 only of study.

Nivolumab+Ipilimumab+Radiation Therapy (RT)

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 origin
• Age \>18 years.
• 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) ≥1000 /mcL
• White blood count (WBC) ≥2000 /mcL
• Platelets ≥75,000 / mcL
• Hemoglobin ≥7.5 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)
• 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 Male CrCl = (140 - age in years) x weight in kg x 1.00 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.
• Patients who have had radiation within 8 weeks prior to protocol registration.
• 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 (\> 12 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 12 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
• Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 12 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Patients are excluded if they have previously received anti-CTLA-4 therapy. Prior anti- PD-1 or anti-PD-L1 therapy is permitted with 6-month washout period unless the following treatment-related toxicities are present:
• Any toxicity NCI CTCAE grade \>/= 3 from previous immunotherapy that did not resolve to grade 1 with or without immunosuppressive therapy. Patients must be off all immunosuppressive therapy prior to enrollment.
• Myocarditis, any grade.
• Pneumonitis, any grade.
• Patients with grade 2 hepatitis or colitis will be evaluated on a case-by-case basis and may be included only after consultation with a Gastroenterologist and the study physician.
• Has a known history of active TB (Bacillus Tuberculosis).
• No active or chronic HBV or HCV. Patients are excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. Subjects with a history of HBV or HCV require documentation of treatment completion, further testing is not required.
• 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.

Sponsors & Collaborators

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

Study Sites (3)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Interventions

Nivolumab; Ipilimumab; Radiotherapy

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

• Theodore S Hong, 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: Principal Investigator

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 5, 2020
• Study Start: October 5, 2020
• Primary Completion: December 1, 2023
• Study Completion: June 1, 2024
• Last Updated: September 8, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (3)