Clinical Trials /

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

NCT03376659

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab Plus CV301 With Maintenance Chemotherapy in Metastatic Colorectal or Pancreatic Adenocarcinoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2017-1189
  • NCT ID: NCT03376659

Conditions

  • Metastatic Colorectal Cancer
  • Colorectal Adenocarcinoma
  • Pancreatic Adenocarcinoma
  • Metastatic Pancreatic Cancer

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Phase I - Safety
CV301Phase I - Safety
CapecitabineXelodaPhase I - Safety
BevacizumabAvastinPhase I - Safety

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase I - SafetyExperimentalMVA-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)
  • Durvalumab
  • CV301
  • Capecitabine
  • Bevacizumab
Phase II - Colorectal Cancer ArmExperimentalMVA-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
  • Durvalumab
  • CV301
  • Capecitabine
  • Bevacizumab
Phase II - Pancreatic Cancer ArmExperimentalMVA-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
  • Durvalumab
  • CV301
  • Capecitabine

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase II dose of durvalumab
Time Frame:6 months
Safety Issue:
Description:The Recommended Phase II dose of durvalumab in the combination of durvalumab plus CV301 with maintenance chemotherapy as determined by the Phase I design

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:1 year
Safety Issue:
Description:To determine the objective response rate
Measure:Progression free survival (PFS)
Time Frame:1 year
Safety Issue:
Description:To determine the progression free survival
Measure:Overall survival (OS)
Time Frame:1 year
Safety Issue:
Description:To determine the overall survival
Measure:Disease control rate (DCR)
Time Frame:4 months
Safety Issue:
Description:To determine the disease control rate
Measure:Tolerability and safety of the combination as determined by the number of treatment emergent adverse events
Time Frame:1 year
Safety Issue:
Description:Tolerability and safety of the combination during the Phase II portion
Measure:Duration of response
Time Frame:1 year
Safety Issue:
Description:To determine the duration of response

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Georgetown University

Trial Keywords

  • PD-L1

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