Durvalumab Plus CV301 With Maintenance Chemotherapy in Metastatic Colorectal or Pancreatic Adenocarcinoma

NCT03376659 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 2017-1189
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer; Colorectal Adenocarcinoma; Pancreatic Adenocarcinoma; Metastatic Pancreatic Cancer

Keywords

PD-L1

Outcome Measures

Primary Outcomes (3)

• Recommended Phase II Dose of Durvalumab

  The Recommended Phase II dose of durvalumab in the combination of durvalumab plus CV301 with maintenance chemotherapy as determined by the Phase I design

  6 months

• Progression Free Survival (PFS) Colorectal Cancer

  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

  24 months

• Progression Free Survival (PFS) Pancreatic Cancer

  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

  24 months

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  1 year

• Progression Free Survival (PFS)

  24 months

• Overall Survival (OS)

  4 years

• Disease Control Rate (DCR)

  4 months

• Tolerability and Safety of the Combination

  2 years

Study Arms (3)

Phase I - Safety

EXPERIMENTAL

* 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)

Drug: Durvalumab; Biological: CV301; Drug: Capecitabine; Drug: Bevacizumab

Phase II - Colorectal Cancer Arm

EXPERIMENTAL

* 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

Drug: Durvalumab; Biological: CV301; Drug: Capecitabine; Drug: Bevacizumab

Phase II - Pancreatic Cancer Arm

EXPERIMENTAL

* 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

Drug: Durvalumab; Biological: CV301; Drug: Capecitabine

Interventions

Durvalumab DRUG

750mg IV q2 weeks

Also known as: MEDI4736

Phase I - Safety; Phase II - Colorectal Cancer Arm; Phase II - Pancreatic Cancer Arm

CV301 BIOLOGICAL

MVA-BN-CV301 (prime) - two priming doses of 1.6 x 109 infectious units/0.5 mL (Inf.U) given subcutaneously (s.c.) FPV-CV301 (boost) - dosed at 1 × 109 Inf.U/0.5 mL given s.c.

Phase I - Safety; Phase II - Colorectal Cancer Arm; Phase II - Pancreatic Cancer Arm

Capecitabine DRUG

1000mg orally twice a day, Monday - Friday Weekly

Also known as: Xeloda

Phase I - Safety; Phase II - Colorectal Cancer Arm; Phase II - Pancreatic Cancer Arm

Bevacizumab DRUG

5mg/kg IV q2weeks

Also known as: Avastin

Phase I - Safety; Phase II - Colorectal Cancer Arm

Eligibility Criteria

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

You may qualify if:

• 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:
• Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin ≥ 9.0 g/dL
• Renal function: Serum creatinine ≤ 1.5 X upper normal limit of institution's normal range OR creatinine clearance ≥ 40 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. Creatinine clearance should be determined by the Cockcroft-Gault formula (below) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
• Females:

You may not qualify if:

• 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
• High dose steroid pre-treatment for CT contrast dye allergy is allowed, provided the dose(s) of steroids is(are) given at least 1 week prior to starting the study medications
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan
• o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• Positive test for HIV infection

Sponsors & Collaborators

• Georgetown University: lead
• Mayo Clinic: collaborator
• Indiana University: collaborator
• Emory University: collaborator
• National Cancer Institute (NCI): collaborator
• George Mason University: collaborator
• Thomas Jefferson University: collaborator
• MedImmune LLC: collaborator
• Bavarian Nordic: collaborator

Study Sites (1)

Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Pancreatic Neoplasms

Interventions

durvalumab; Capecitabine; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Benjamin Weinberg, MD
• Organization: Georgetown University

benjamin.a.weinberg@gunet.georgetown.edu

202-444-2223

Study Officials

• Michael Pishvaian, MD PhD

  Johns Hopkins University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: December 18, 2017
• Study Start: August 8, 2018
• Primary Completion: August 30, 2021
• Study Completion: August 1, 2023
• Last Updated: February 5, 2024
• Results First Posted: January 10, 2023

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)