A Phase II Study of Niraparib and Dostarlimab With Radiation in Patients With Metastatic Pancreatic Cancer
Overview
- Phase
- Phase 2
- Intervention
- Niraparib
- Conditions
- Pancreatic Cancer
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Disease Control Rate With RECIST 1.1 Criteria
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
This research is being done to see how the combination of dostarlimab, niraparib, and radiation therapy works in controlling metastatic pancreatic cancer.
Detailed Description
This two-stage single arm phase II trial will evaluate the efficacy of niraparib with dostarlimab and radiation therapy in patients with metastatic pancreatic cancer The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. The names of the experimental interventions involved in this study are: * Dostarlimab * Niraparib * Radiation Therapy It is expected that about 25 people will take part in this research study. An initial 15 participants will be enrolled during the first stage and evaluated for treatment disease control, if none of the initial 15 participants achieve disease control the study will be terminated. It is expected participants will be on the research study for as long as the experimental interventions are safe, and their metastatic pancreatic cancer does not progress with up to 5 years of follow up after participants stop taking the experimental interventions. This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The U.S. Food and Drug Administration (FDA) has not approved dostarlimab as a treatment for any disease. Dostarlimab is a type of antibody (a protein that attaches to other cells to fight off infection) that is believed to work by attaching to a protein called PD-1 on Tcells. This PD-1 protein controls parts of the immune system (the system in the body that fights off infections and diseases) by shutting down certain immune responses responsible for recognizing and destroying cancer cells. The investigators believe that dostarlimab will inhibit the PD-1 protein, thus allowing the immune cells to recognize and destroy cancer cells. The FDA has not approved niraparib for metastatic pancreatic cancer, but it has been approved for other uses. Niraparib is a type of drug called a "PARP inhibitor", which blocks DNA (the genetic material of cells) damage from being repaired or may prevent damage from occurring in the first place. In cancer treatment, inhibiting PARP may help kill cancer cells by not allowing the cancer cells to repair its DNA damage or prevent DNA damage from occurring. It is believed that the combination of dostarlimab, niraparib, and radiation therapy may have a greater effect on metastatic pancreatic cancer cells than when these interventions are used alone.
Investigators
Julie Koenig
Principal Investigator
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed metastatic adenocarcinoma of pancreatic origin.
- •Age \> 18 years.
- •ECOG performance status ≤
- •Life expectancy of greater than 3 months.
- •Participants must have normal organ and marrow function as defined below:
- •leukocytes ≥ 2,000/mcL
- •absolute neutrophil count ≥ 1,500/mcL
- •platelets ≥ 100,000/mcL
- •hemoglobin ≥ 9 g/dL
- •AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal(subjects with liver metastases can have an AST (SGOT) ≤ 5 x ULN
Exclusion Criteria
- •Participants who meet any of the following criteria will be excluded:
- •Systemic anticancer or biological therapy including prior chemotherapy, immunotherapy, targeted small molecule therapy within 14 days prior to investigational agent, 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. Participants with ≤ grade 2 neuropathy are an exception to these criteria and may qualify for the study. If the participant received major surgery, then they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Received investigational therapy ≥ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
- •Major surgery ≤ 3 weeks prior to initiating protocol therapy and/or not recovered from any surgical effects.
- •Received radiation therapy encompassing \>20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to day 1 of protocol therapy.
- •Received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy
- •Received colony-stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior to initiating protocol therapy. Known history of Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
- •Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- •Active, known or suspected autoimmune disease that has required systemic treatment within the past 2 years other than 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.
- •Any 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. Participants 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 \> 10 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.
Arms & Interventions
Niraparib+Dostarlimab + Radiation
Each study treatment cycle lasts 21 days * Niraparib oral, once a day, predetermined dose.Dosing will commence on cycle 1 day 1 and will continue until the participant is taken off treatment * Dostarlimab by intravenous infusion once every cycle for as long as they remain on the study * Radiation therapy on every other week day of cycle 2 only. Radiation will begin on Cycle 2 Day 1
Intervention: Niraparib
Niraparib+Dostarlimab + Radiation
Each study treatment cycle lasts 21 days * Niraparib oral, once a day, predetermined dose.Dosing will commence on cycle 1 day 1 and will continue until the participant is taken off treatment * Dostarlimab by intravenous infusion once every cycle for as long as they remain on the study * Radiation therapy on every other week day of cycle 2 only. Radiation will begin on Cycle 2 Day 1
Intervention: Dostarlimab
Niraparib+Dostarlimab + Radiation
Each study treatment cycle lasts 21 days * Niraparib oral, once a day, predetermined dose.Dosing will commence on cycle 1 day 1 and will continue until the participant is taken off treatment * Dostarlimab by intravenous infusion once every cycle for as long as they remain on the study * Radiation therapy on every other week day of cycle 2 only. Radiation will begin on Cycle 2 Day 1
Intervention: Radiation
Outcomes
Primary Outcomes
Disease Control Rate With RECIST 1.1 Criteria
Time Frame: up to 17 months
Disease control rate (DCR) is the percentage of participants who experienced a complete response (CR), partial response (PR), or stable disease (SD) assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria below. * CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * PR = At least 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum diameters. * SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the baseline sum diameters while on study. * Progressive Disease (PD) = At least 20% increase in the sum of longest diameters of target lesions, taking as reference the baseline sum diameters while on study. Appearance of one or more new lesions is also considered progression.
Secondary Outcomes
- Disease Control Rate With irRECIST Criteria(up to 17 months)
- Progression-free Survival(up to 17 months)
- Overall Survival(up to 17 months)
- Number of Treatment-Related Adverse Events Per CTCAE v5.0(up to 19 weeks)