Clinical Trials /

Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines

NCT02432378

Description:

Please Note : This study will be moving from the Phase I portion of the study into the Phase II portion of the study with an Anticipated start date of March 1, 2020. 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.

Related Conditions:
  • Fallopian Tube Adenocarcinoma
  • Fallopian Tube Carcinosarcoma
  • Ovarian Adenocarcinoma
  • Ovarian Carcinosarcoma
  • Primary Peritoneal Carcinosarcoma
  • Primary Peritoneal Serous Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 11-128
  • SECONDARY ID: 5P01CA132714
  • NCT ID: NCT02432378

Conditions

  • Cancer of Ovary
  • Cancer of the Ovary
  • Neoplasms, Ovarian
  • Ovarian Cancer
  • Ovary Cancer
  • Ovary Neoplasms

Interventions

DrugSynonymsArms
Cisplatin + celecoxib + DC vaccineCisplatin + Celecoxib + DC Vaccine
Cisplatin + CKM + Celecoxib + DC VaccineCisplatin + CKM + Celecoxib + DC Vaccine

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cisplatin + Celecoxib + DC VaccineExperimentalCisplatin 50 mg/m2 by IP once per cycle (21 days) + celecoxib daily 200 mg by mouth daily + intranodal vaccine injections once per cycle
    Cisplatin + CKM + Celecoxib + DC VaccineExperimentalCisplatin 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

      Eligibility Criteria

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

      Primary Outcome Measures

      Measure:Change in the number of CD8+ tumor infiltrating T cells in the peritoneal fluid.
      Time Frame:8 weeks
      Safety Issue:
      Description:The difference in CD8+ tumor infiltrating T cells over 3 cycles of platinum based chemotherapy plus immunotherapy compared with baseline.

      Secondary Outcome Measures

      Measure:Change in the number of CD3+CD8+ T cells in the peritoneal fluid.
      Time Frame:8 weeks
      Safety Issue:
      Description:
      Measure:Change in the number of effector CD8+ T cells in the peritoneal fluid.
      Time Frame:8 weeks
      Safety Issue:
      Description:
      Measure:Change in the number of CD4+ T cells in the peritoneal fluid.
      Time Frame:8 weeks
      Safety Issue:
      Description:
      Measure:Change in the number of Tregs in the peritoneal fluid.
      Time Frame:8 weeks
      Safety Issue:
      Description:
      Measure:Change in the number of myeloid-derived suppressor cells in the peritoneal fluid.
      Time Frame:8 weeks
      Safety Issue:
      Description:

      Details

      Phase:Phase 1/Phase 2
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Pawel Kalinski

      Last Updated

      January 19, 2017