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

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ClinicalTrials.gov Identifier: NCT03376659
Recruitment Status : Not yet recruiting
First Posted : December 18, 2017
Last Update Posted : August 13, 2018
Sponsor:
Collaborators:
Mayo Clinic
Indiana University
Emory University
National Cancer Institute (NCI)
George Mason University
Thomas Jefferson University
MedImmune LLC
Bavarian Nordic, Inc.
Information provided by (Responsible Party):
Georgetown University

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Colorectal Adenocarcinoma Pancreatic Adenocarcinoma Metastatic Pancreatic Cancer Drug: Durvalumab Biological: CV301 Drug: Capecitabine Drug: Bevacizumab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: 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)
Drug: Durvalumab
750mg IV q2 weeks
Other Name: MEDI4736

Biological: CV301

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.


Drug: Capecitabine
1000mg orally twice a day, Monday - Friday Weekly
Other Name: Xeloda

Drug: Bevacizumab
5mg/kg IV q2weeks
Other Name: Avastin

Experimental: 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
Drug: Durvalumab
750mg IV q2 weeks
Other Name: MEDI4736

Biological: CV301

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.


Drug: Capecitabine
1000mg orally twice a day, Monday - Friday Weekly
Other Name: Xeloda

Drug: Bevacizumab
5mg/kg IV q2weeks
Other Name: Avastin

Experimental: 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
Drug: Durvalumab
750mg IV q2 weeks
Other Name: MEDI4736

Biological: CV301

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.


Drug: Capecitabine
1000mg orally twice a day, Monday - Friday Weekly
Other Name: Xeloda




Primary Outcome Measures :
  1. 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

  2. 8.5 month progression free survival rate (PFS8.5mos) [ Time Frame: 8.5 months ]
    To determine the 8.5 month progression free survival rate (PFS8.5mos) 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

  3. 4 month progression free survival rate (PFS4mos) [ Time Frame: 4 months ]
    To determine the 4 month progression free survival rate (PFS4mos) 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 Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 1 year ]
    To determine the objective response rate

  2. Progression free survival (PFS) [ Time Frame: 1 year ]
    To determine the progression free survival

  3. Overall survival (OS) [ Time Frame: 1 year ]
    To determine the overall survival

  4. Disease control rate (DCR) [ Time Frame: 4 months ]
    To determine the disease control rate

  5. Tolerability and safety of the combination as determined by the number of treatment emergent adverse events [ Time Frame: 1 year ]
    Tolerability and safety of the combination during the Phase II portion

  6. Duration of response [ Time Frame: 1 year ]
    To determine the duration of response



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Stable on, or responding to 1st line therapy for metastatic disease

    1. At least 8 and not more than 16 weeks after initiating 1st line therapy for metastatic disease
    2. Tumor stability/response on 1st line therapy will be determined as per RECIST 1.1
  3. 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
  4. Disease that is amenable to serial biopsies
  5. ECOG performance status 0-1
  6. Age >= 18 years
  7. Blood pressure <160/100 mmHg
  8. Adequate hepatic, bone marrow, and renal function:

    1. Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin ≥ 9.0 g/dL
    2. 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:

      Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)

    3. Hepatic function: AST and ALT ≤ 2.5 X the upper normal limit of institution's normal range. Non-fasting bilirubin ≤ 1.5 X the upper normal limit of institution's normal range.
  9. Partial Thromboplastin Time (PTT) must be ≤ 1.5 X upper normal limit of institution's normal range and INR (International Normalized Ratio) ≤ 1.5. Subjects on anticoagulant (such as coumadin) will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator. Due to the drug-drug interaction between warfarin and capecitabine, alternate anticoagulation should be considered.
  10. Life expectancy > 12 weeks.
  11. Women of childbearing potential must have a negative serum or urine pregnancy test within 28 days prior to initiation of treatment AND confirmed prior to initiation of treatment on Day 1.
  12. Alternatively, female subjects must be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy).
  13. Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consents, approved by the Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

  1. Any prior immunotherapy or vaccine therapy
  2. 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
  3. 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
  4. 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.

  5. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  6. Positive test for HIV infection
  7. Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening)

    o Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive IgG antibody to hepatitis B core antigen [anti-HBc] OR negative HBV viral load by PCR) are eligible.

  8. Active hepatitis C

    o Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.

  9. Active tuberculosis OR known history of previous clinical diagnosis of tuberculosis
  10. Severe infections within 4 weeks prior to Week 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia

    o Any course of oral or IV antibiotics must have been completed at least 2 weeks prior to the first dose of study medications

  11. Signs or symptoms of infection within 2 weeks prior to Week 1, Day 1
  12. Received oral or IV antibiotics within 2 weeks prior to Week 1, Day 1

    o Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.

  13. Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  14. Administration of a live, attenuated vaccine within 30 days before Week 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study

    o Influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccine (e.g., FluMistTM) within 4 weeks prior to Week 1, Day 1 or at any time during the study.

  15. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  16. Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 2 weeks prior to initiation of study treatment, with the following exceptions:

    • Hormone-replacement therapy or oral contraceptives
    • Herbal therapy > 1 week before Week 1, Day 1 (herbal therapy intended as anti-cancer therapy must be discontinued at least 1 week before Week 1, Day 1)
  17. CNS metastases including a history of leptomeningeal carcinomatosis
  18. Subjects with uncontrolled seizures
  19. The subject has had another active malignancy within the past five years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin. Questions regarding the inclusion of individual subjects should be directed to the Principle Investigator.
  20. Cardiovascular disease including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months
  21. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
  22. Life-threatening visceral disease or other severe concurrent disease
  23. Grade ≥2 proteinuria at screening (or known prior)
  24. Women who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not employing two highly effective and acceptable forms of contraception throughout their participation in the study and for 90 days after last dose of study drug.
  25. Patients concurrently receiving any other investigational agents.
  26. History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab or any excipient or any egg products
  27. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03376659


Locations
United States, District of Columbia
Lombardi Comprehensive Cancer Center Not yet recruiting
Washington, District of Columbia, United States, 20007
Contact: Sarah Parenti    202-687-8350    sep88@georgetown.edu   
Principal Investigator: Michael Pishvaian, MD PhD         
Sponsors and Collaborators
Georgetown University
Mayo Clinic
Indiana University
Emory University
National Cancer Institute (NCI)
George Mason University
Thomas Jefferson University
MedImmune LLC
Bavarian Nordic, Inc.
Investigators
Study Chair: Michael Pishvaian, MD PhD Georgetown University

Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT03376659     History of Changes
Other Study ID Numbers: 2017-1189
First Posted: December 18, 2017    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Georgetown University:
PD-L1

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenocarcinoma
Pancreatic Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Bevacizumab
Capecitabine
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites