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Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines

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ClinicalTrials.gov Identifier: NCT02432378
Recruitment Status : Recruiting
First Posted : May 4, 2015
Last Update Posted : June 19, 2019
Sponsor:
Collaborators:
Hemispherx Biopharma
National Cancer Institute (NCI)
University of Pittsburgh
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE April 8, 2015
First Posted Date  ICMJE May 4, 2015
Last Update Posted Date June 19, 2019
Study Start Date  ICMJE July 2015
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 28, 2015)
  • Change in the number of CD8+ tumor infiltrating T cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
    The difference in CD8+ tumor infiltrating T cells over 3 cycles of platinum based chemotherapy plus immunotherapy compared with baseline.
  • Number of adverse events for the different combinations [ Time Frame: 8 weeks ]
    2 patients will be treated and observed for 2 cycles on each of the dose tiers to identify the acceptable dose of IFN in combination with the other protocol drugs/vaccine for the second phase of the trial.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02432378 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2015)
  • Change in the number of CD3+CD8+ T cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the number of effector CD8+ T cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the number of CD4+ T cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the number of Tregs in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the number of myeloid-derived suppressor cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 28, 2015)
  • Change in the number of TH1 cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the number of natural killer cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the number of dendritic cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the number of activated macrophages in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the number of tumor cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of CCL3 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of CCL4 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of CCL5 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of CXCL9 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of CXCL10 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of CXCL11 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of CXCL12 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of GrB in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of IFN gamma in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of FoxP3 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of IDO in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of NO in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of IL-10 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the concentration of COX-2 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  • Change in the number of CD3+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CD4+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CD8+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CD11b+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CD11c+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of GrB+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of FoxP3+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of IDO+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CCL3 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CCL4 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CCL5 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CXCL9 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CXCL10 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CXCL11 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CCL22 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of CXCL12 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of GrB cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of IFN gamma cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of FoxP3 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of IDO cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of NO cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of IL-10 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  • Change in the number of COX-2 cells in the tumor tissue. [ Time Frame: 8 weeks ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines
Official Title  ICMJE A Phase 1-2 Neoadjuvant Dose Finding, Safety, and Immunologic Efficacy Trial of Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer and Tumor-Specific Intranodal Autologous Alpha-DC1 Vaccines
Brief Summary The main goal of this research study is to determine if intraperitoneal (IP) administration of cisplatin in addition to an investigational vaccine (the DC vaccine) with or without an investigational drug combination of IP rintatolimod, IP interferon alpha-2b (IFN), and oral celecoxib, has any effect, good or bad, on recurrent ovarian cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cancer of Ovary
  • Cancer of the Ovary
  • Neoplasms, Ovarian
  • Ovarian Cancer
  • Ovary Cancer
  • Ovary Neoplasms
Intervention  ICMJE
  • Biological: Cisplatin + celecoxib + DC vaccine
    Cisplatin 50 mg/m2 by IP once per cycle (21 days) + celecoxib daily 200 mg by mouth daily + intranodal vaccine injections once per cycle
  • Biological: Cisplatin + CKM + Celecoxib + DC Vaccine
    Cisplatin 50 mg/m2 by IP once per cycle (21 days) + celecoxib daily 200 mg by mouth daily + IFN by IP once per cycle + rintatolimod 200 mg by IP once per cycle + intranodal vaccine injections once per cycle
Study Arms  ICMJE
  • Experimental: Cisplatin + Celecoxib + DC Vaccine
    Cisplatin 50 mg/m2 by IP once per cycle (21 days) + celecoxib daily 200 mg by mouth daily + intranodal vaccine injections once per cycle
    Intervention: Biological: Cisplatin + celecoxib + DC vaccine
  • Experimental: Cisplatin + CKM + Celecoxib + DC Vaccine
    Cisplatin 50 mg/m2 by IP once per cycle (21 days) + celecoxib daily 200 mg by mouth daily + IFN by IP once per cycle + rintatolimod 200 mg by IP once per cycle + intranodal vaccine injections once per cycle
    Intervention: Biological: Cisplatin + CKM + Celecoxib + DC Vaccine
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: April 28, 2015)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have peritoneal recurrence of epithelial adenocarcinoma or carcinosarcoma of ovarian, tubal, or peritoneal origin. Histologic documentation of the original primary tumor is required via the pathology report. Original tumor blocks from primary diagnosis will be reviewed by our study pathologist at Magee.
  • Patients must have completed front-line taxane/platinum-based therapy of their primary tumor with a progression free interval of greater than 6 months from last therapy and measurable relapsed disease must be present in the abdomen greater than 1 cm.
  • Patients must have documentation of a defined initial progression free interval (PFI 1) of greater than 6 months following front-line therapy.
  • Patients must have documentation of relapse that includes either doubling of CA125 serum levels confirmed by measurements greater than one week apart or identification of a new measurable lesion greater than 1 cm in the peritoneal cavity either by CT/MRI, PET/CT scan or physical exam (expanding pockets of ascites fluid that may serve as an alternative source of tumor cells) if the index lesion is not accessible for biopsy for vaccine formulation. Recurrence outside the peritoneal cavity will be accessed using standard RECIST criteria.
  • Patients must be reasonable candidates for laparoscopy and IP platinum regimen with no prior evidence of clinically significant intra-abdominal adhesions, persistent abdominal wall infections, renal toxicity, or bowel obstruction.
  • Prior to enrollment, the CA125 should have been elevated to at least double the level seen at the nadir value following the first complete response and measurable intraperitoneal disease that can be identified radiologically and accessed by laparoscopy/laparotomy for a biopsy and peritoneal catheter placement.
  • Patients must have documented available tumor greater than 1 cm of bulk tumor mass or 200 cc of ascites fluid for tumor isolation prior to starting chemotherapy.
  • Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to the first date of treatment on this study.
  • Patient may be required to undergo leukapheresis (depending on the study phase/cohort) and must agree to leukapheresis if so assigned.
  • Patients must agree to appropriate clinical monitoring to receive the study regimens.
  • Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/µL, equivalent to CTCAE v4 grade 1. Platelets greater than or equal to 100,000/µL; hemoglobin greater than or equal to 8.0 g/dL.
  • Renal function: creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v4 grade 1.
  • Hepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE v4 grade 1). SGOT and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v4 grade 1).
  • Patients who have signed informed consent and authorization permitting release of personal health information.
  • Patients must be ≥ 18 years of age.
  • Patients must have a GOG Performance Status of 0 or 1.

Exclusion Criteria:

  • Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis).
  • Patients with a known allergy to cisplatin chemotherapy. Patients with carboplatin allergy may be included if they tolerate a test dose of IV cisplatin given in monitored floor conditions.
  • Patients being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH), or systemic corticosteroids.
  • Patients with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; patients who have acquired, hereditary, or congenital immunodeficiencies.
  • Patients with uncontrolled diseases other than cancer will be excluded.
  • Patients who are pregnant or nursing.
  • Patients who have contraindications to the use of NSAID's like chronic renal failure, coronary artery disease, or bleeding ulcers.
  • Patients with tumors of low malignant potential, except ovarian pseudomyxoma or with no peritoneal disease.
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
  • Patients with previous pelvic radiation therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Emily Staniszewski 412-641-3578 staniszewskie@upmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02432378
Other Study ID Numbers  ICMJE 11-128
5P01CA132714 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE
  • Hemispherx Biopharma
  • National Cancer Institute (NCI)
  • University of Pittsburgh
Investigators  ICMJE
Principal Investigator: Robert P Edwards, MD University of Pittsburgh
PRS Account Roswell Park Cancer Institute
Verification Date June 2019

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