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Trial record 1 of 1 for:    NCT02643303
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A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers

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ClinicalTrials.gov Identifier: NCT02643303
Recruitment Status : Recruiting
First Posted : December 31, 2015
Last Update Posted : August 28, 2019
Sponsor:
Collaborators:
MedImmune LLC
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

Tracking Information
First Submitted Date  ICMJE December 18, 2015
First Posted Date  ICMJE December 31, 2015
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE December 28, 2016
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2019)
Progression-Free Survival (PFS) at 24 weeks [ Time Frame: up to 24 weeks ]
Analyzed by irRECIST
Original Primary Outcome Measures  ICMJE
 (submitted: December 28, 2015)
  • To determine the recommended combination doses of the dosing regimen, based on assessment of toxicity and tolerability. [ Time Frame: 12 months ]
    In the Dose-finding Phase, Cohorts 1A - 1C, the safety and tolerability of each regimen will be evaluated to determine the tolerability of IT or systemic tremelimumab and/or IV durvalumab in combination with polyICLC.
  • Clinical Efficacy will be determined by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) and will be assessed by irRECIST and RECIST1.1. [ Time Frame: up to 6 years ]
Change History Complete list of historical versions of study NCT02643303 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2019)
  • Safety and tolerability [ Time Frame: up to 15 months ]
    Adverse events according to CTCAE V4.03
  • Clinical Efficacy by objective response rate (ORR) [ Time Frame: up to 15 months ]
    assessed by irRECIST
  • Clinical Efficacy by progression-free survival (PFS) [ Time Frame: up to 15 months ]
    assessed by irRECIST
  • Clinical Efficacy by overall survival (OS) [ Time Frame: up to 15 months ]
    assessed by irRECIST
Original Secondary Outcome Measures  ICMJE
 (submitted: December 28, 2015)
  • Individual durvalumab concentrations [ Time Frame: First dose of durvalumab through 3 months after the last dose of study medication ]
  • Individual tremelimumab concentrations after IV and IT administration [ Time Frame: First dose of tremelimumab through 3 months after the last dose of study medication ]
  • Number of subjects that develop changes in detectable antidrug antibodies to durvalumab [ Time Frame: First dose of durvalumab through 6 months after the last dose of study medication ]
  • Number of subjects that develop changes in detectable antidrug antibodies to tremelimumab [ Time Frame: First dose of tremelimumab through 6 months after the last dose of study medication ]
  • Durvalumab and Tremelimumab Immunogenicity [ Time Frame: up to 39 months ]
    Anti-drug antibody samples for the assessment of anti-tremelimumab and anti- durvalumab antibodies will be collected at each time point. Validated electrochemiluminescence assays using the MSD platform will be used for the detection of anti-tremelimumab and antidurvalumab antibodies in human serum.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: December 28, 2015)
Changes in Biomarkers [ Time Frame: Screening through 1 months after the last dose of study medication ]
Evaluate biomarkers that may correlate with clinical activity of durvalumab monotherapy plus Poly ICLC, tremelimumab IV and IT monotherapy plus PolyICLC and durvalumab, tremelimumab and PolyICLC in combination.
 
Descriptive Information
Brief Title  ICMJE A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers
Official Title  ICMJE A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab (MEDI4736) Plus the Toll-like Receptor Agonist PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers
Brief Summary This is an open-label, multicenter Phase 1/2 study of the CTLA-4 antibody, tremelimumab, and the PD-L1 antibody, durvalumab (MEDI4736), in combination with the tumor microenvironment (TME) modulator polyICLC, a TLR3 agonist, in subjects with advanced, measurable, biopsy-accessible cancers.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Head and Neck Squamous Cell Carcinoma
  • Breast Cancer
  • Sarcoma
  • Merkel Cell Carcinoma
  • Cutaneous T-Cell Lymphoma
  • Melanoma
  • Renal Cancer
  • Bladder Cancer
  • Prostate Cancer
  • Testicular Cancer
  • Solid Tumor
Intervention  ICMJE
  • Drug: Durvalumab
    Other Name: MEDI4736
  • Drug: Tremelimumab
  • Drug: Poly ICLC
    Other Name: Hiltonol
Study Arms  ICMJE
  • Experimental: Phase 1, Cohort 1A
    IV Durvalumab + IT/IM polyICLC
    Interventions:
    • Drug: Durvalumab
    • Drug: Poly ICLC
  • Experimental: Phase 1, Cohort 1B
    IV Durvalumab + IV Tremelimumab + IT/IM polyICLC
    Interventions:
    • Drug: Durvalumab
    • Drug: Tremelimumab
    • Drug: Poly ICLC
  • Experimental: Phase 1, Cohort 1C
    IV Durvalumab + IT Tremelimumab + IT/IM polyICLC
    Interventions:
    • Drug: Durvalumab
    • Drug: Tremelimumab
    • Drug: Poly ICLC
  • Experimental: Phase 2 Cohort
    Once the recommended combination doses of the triplet dosing regimen has been determined in Cohort 1C, subsequent subjects will be enrolled into Cohort 2 to receive the recommended combination doses of both checkpoint antibodies in combination with polyICLC.
    Interventions:
    • Drug: Durvalumab
    • Drug: Tremelimumab
    • Drug: Poly ICLC
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 28, 2015)
102
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subjects must have histologic confirmation of advanced, biopsy-accessible, measurable cancers of the following histologies:

    • Non-viral-associated head and neck squamous cell carcinoma (HNSCC) or HPV-associated HNSCC after failure of prior therapy
    • Locally recurrent or metastatic breast cancer
    • Sarcoma
    • Merkel Cell Carcinoma (MCC)
    • Cutaneous T cell Lymphoma (CTCL)
    • Melanoma after failure of available therapies
    • GU cancers with accessible metastases (e.g., bladder, renal)
    • Any solid tumors with masses that are accessible
  2. Subjects with measurable disease, must have at least 2 lesions (1 measurable lesion and 1 biopsy/injectable lesion, which will not need to be measurable).
  3. Any number of prior systemic therapies.
  4. ECOG performance status 0-1.
  5. Laboratory parameters for vital functions should be in the normal range or not clinically significant.

Exclusion Criteria:

  1. Prior treatment with combination CTLA-4 and PD-1/PD-L1 blockade, with the exception of subjects with melanoma.
  2. Participants may not have been treated intratumorally with polyICLC.
  3. Subjects with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any active brain metastases, or, within 6 months of the first date of treatment on this study, history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage.
  4. Active, suspected or prior documented autoimmune disease, clinically significant cardiovascular disease or clinically uncontrolled hypertension.
  5. History of pneumonitis or interstitial lung disease or any unresolved immune-related adverse events following prior biological therapy.
  6. Other malignancy within 2 years prior to entry into the study, except for those treated with surgical therapy only (e.g., localized low-grade cervical or prostate cancers).
  7. Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who require drainage gastrostomy tube and/or parenteral hydration or nutrition.
  8. Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C positivity. Antibody to Hepatitis B or C without evidence of active infection may be allowed.
  9. History of severe allergic reactions to any unknown allergens or any components of the study drugs.
  10. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
  11. History of allogeneic organ transplant.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kristen Aufiero Ramirez 212-450-1515 clintrialinformation@licr.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02643303
Other Study ID Numbers  ICMJE LUD2014-011
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ludwig Institute for Cancer Research
Study Sponsor  ICMJE Ludwig Institute for Cancer Research
Collaborators  ICMJE
  • MedImmune LLC
  • Cancer Research Institute, New York City
Investigators  ICMJE
Study Chair: Craig L Slingluff, Jr., MD University of Virginia
Study Chair: Nina Bhardwaj, MD, PhD Tisch Cancer Institute Ichan School of Medicine at Mount Sinai
PRS Account Ludwig Institute for Cancer Research
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP