A Phase I/II Trial of the PD-L1 Inhibitor, Durvalumab Plus CV301 in Combination With Maintenance Chemotherapy for Patients With Metastatic Colorectal or Pancreatic Adenocarcinoma
Overview
- Phase
- Phase 1
- Intervention
- Durvalumab
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Georgetown University
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Recommended Phase II Dose of Durvalumab
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a dual arm, open label phase I/II study to evaluate the safety and clinical activity of the combination of durvalumab with CV301 in combination with maintenance chemotherapy for patients with metastatic colorectal or pancreatic cancer whose disease is stable on, or responding to 1st line therapy for metastatic disease. Patients with metastatic colorectal or pancreatic adenocarcinoma who still have an adequate performance status and normal hepatic and renal function will be eligible.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically proven metastatic pancreatic or colorectal adenocarcinoma with measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST 1.1 criteria.
- •Stable on, or responding to 1st line therapy for metastatic disease
- •At least 8 and not more than 16 weeks after initiating 1st line therapy for metastatic disease
- •Tumor stability/response on 1st line therapy will be determined as per RECIST 1.1
- •Prior adjuvant chemotherapy is allowed, as long as a minimum of 3 months (for pancreatic cancer) and 6 months (for colorectal cancer) has passed between the completion of adjuvant therapy and the start of first line therapy
- •Disease that is amenable to serial biopsies
- •ECOG performance status 0-1
- •Age \>= 18 years
- •Blood pressure \<160/100 mmHg
- •Adequate hepatic, bone marrow, and renal function:
Exclusion Criteria
- •Any prior immunotherapy or vaccine therapy
- •History of active or prior documented autoimmune disease within the past 2 years including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, auto-immune Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, with the following caveats:
- •Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
- •Patients with Grave's disease, vitiligo, autoimmune alopecia, or psoriasis not requiring systemic treatment (within the past 2 years) are eligible upon consultation with the Study Chairs
- •Patients with questionable diagnosis of autoimmune disease who have never been treated with immunosuppressive regimen and have no ongoing symptoms at the time of enrollment may be eligible after discussion with medical monitor and principle investigator
- •Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNFα antagonists) within 28 days prior to Week 1, Day 1
- •Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Study Co-chairs.
- •The use of inhaled, intranasal, ophthalmic or topical corticosteroids is allowed
- •The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension is allowed.
- •Physiologic doses of systemic corticosteroids at doses which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
Arms & Interventions
Phase I - Safety
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks (colorectal cancer patients only)
Intervention: Durvalumab
Phase I - Safety
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks (colorectal cancer patients only)
Intervention: CV301
Phase I - Safety
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks (colorectal cancer patients only)
Intervention: Capecitabine
Phase I - Safety
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks (colorectal cancer patients only)
Intervention: Bevacizumab
Phase II - Colorectal Cancer Arm
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks
Intervention: Durvalumab
Phase II - Colorectal Cancer Arm
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks
Intervention: CV301
Phase II - Colorectal Cancer Arm
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks
Intervention: Capecitabine
Phase II - Colorectal Cancer Arm
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly * Bevacizumab - q2weeks
Intervention: Bevacizumab
Phase II - Pancreatic Cancer Arm
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly
Intervention: Durvalumab
Phase II - Pancreatic Cancer Arm
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly
Intervention: CV301
Phase II - Pancreatic Cancer Arm
* MVA-BN-CV301 (prime) - Day 1 and Day 29. * FPV-CV301 (boost) - Day 1 of Weeks 9, 13, 17, 21, 25, 37, and q24 weeks starting week 53. * Durvalumab - q2 weeks * Capecitabine - twice a day, Monday - Friday Weekly
Intervention: Capecitabine
Outcomes
Primary Outcomes
Recommended Phase II Dose of Durvalumab
Time Frame: 6 months
The Recommended Phase II dose of durvalumab in the combination of durvalumab plus CV301 with maintenance chemotherapy as determined by the Phase I design
Progression Free Survival (PFS) Colorectal Cancer
Time Frame: 24 months
To determine the progression free survival (PFS) of durvalumab plus CV301 in combination with maintenance capecitabine and bevacizumab in patients with metastatic colorectal cancer, whose disease is stable on, or responding to 1st line therapy for metastatic disease
Progression Free Survival (PFS) Pancreatic Cancer
Time Frame: 24 months
To determine the progression free survival rate (PFS) of durvalumab plus CV301 in combination with maintenance capecitabine in patients with metastatic pancreatic cancer, whose disease is stable on, or responding to 1st line therapy for metastatic disease
Secondary Outcomes
- Objective Response Rate (ORR)(1 year)
- Disease Control Rate (DCR)(4 months)
- Progression Free Survival (PFS)(24 months)
- Overall Survival (OS)(4 years)
- Duration of Response(1 year)
- Tolerability and Safety of the Combination(2 years)