Nivolumab + Ipilimumab + Radiation in MSS Pancreatic Cancer

NCT04361162 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 19-587
• Study Type: interventional
• Target: 30
• 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 microsatellite stable pancreatic cancer. The names of the study interventions involved in this study are:

• Ipilimumab
• Nivolumab
• Radiation Therapy

Conditions

Pancreatic Cancer; Metastatic Pancreatic Cancer

Keywords

Pancreatic Cancer; Metastatic Pancreatic Cancer; Metastatic, Microsatellite Stable Pancreatic Cancer; Immunotherapy; Radiation therapy

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Overall response rate (ORR) will be evaluated by RECIST. Nivolumab and ipilimumab combined with radiation will be considered to have promising activity in metastatic MSS pancreatic cancer if at least 3 of 30 patients were to achieve CR or PR.

  6 weeks

Secondary Outcomes (4)

• Disease control rate (DCR)

  Up to 5 yrs

• Number of Participants with Treatment Related Adverse Events as Assessed NCI CTCAE 5.0 guidelines

  Up to 5 years

• Progression-free survival (PFS)

  Up to 5 years

• Overall survival (OS) in patients

  Up to 5 years

Study Arms (1)

Nivolumab + Ipilimumab + Radiation

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits, (Study cycles are 6 weeks.) * Nivolumab via iv, at predetermined dose every 2 weeks for duration of study. * Ipilimumab via iv at a predetermined dose on day 1 of 4 study cycles. * Radiation treatments will be administered every other weekday or 2 days during week 1 of cycle 1.

Drug: Nivolumab; Drug: Ipilimumab; Radiation: Radiation

Interventions

Nivolumab DRUG

Nivolumab is a type of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer

Also known as: Opdivo

Nivolumab + Ipilimumab + Radiation

Ipilimumab DRUG

Ipilimumab is a type of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Ipilimumab work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer

Also known as: Yervoy

Nivolumab + Ipilimumab + Radiation

Radiation RADIATION

3D Conformal Radiotherapy to shrink or kill tumors

Also known as: RT

Nivolumab + Ipilimumab + Radiation

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 metastatic MSS adenocarcinoma of pancreatic origin
• Age \>18 years.
• ECOG performance status \<2
• 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.
• 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: ≤ Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) OR
• Measured or calculated Creatinine clearance should be calculated per institutional standard: ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
• (GFR can also be used in place of creatinine or CrCl)
• 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 (dexamethasone 1.5mg or prednisone \<10mg) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses dexamethasone 1.5mg or prednisone \<10mg 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, dexamethasone 1.5mg or prednisone \<10mg. 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.
• Patients are excluded if they have previously received anti-CTLA-4 therapy. Prior PD-1 or PDL1 therapy will be permitted.
• Has a known history of active TB (Bacillus Tuberculosis)
• Known HBV or HCV. (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 (3)

Massachusetts General Hospital

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

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis

Interventions

Nivolumab; Ipilimumab; Radiation

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

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: April 22, 2020
• First Posted: April 24, 2020
• Study Start: May 18, 2020
• Primary Completion: October 1, 2022
• Study Completion (Estimated): October 1, 2026
• 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)