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Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02432378
Recruitment Status : Suspended
First Posted : May 4, 2015
Last Update Posted : October 19, 2022
Sponsor:
Collaborators:
AIM ImmunoTech Inc.
National Cancer Institute (NCI)
University of Pittsburgh
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:

This study will evaluate the immunologic and potential clinical effectiveness of intensive locoregional sequential intraperitoneal (IP) cisplatin (IPC) with intravenous (iv) paclitaxel followed by peritoneal infusion of a chemokine modulatory (CKM) regimen composed of a cocktail of IP rintatolimod and interferon-alpha (IFNα) for patients with advanced stage ovarian cancer (III-IV) at primary neoadjuvant setting.

In the safety phase I phase, we determined the tolerable dose of IPC-CKM. In this phase 2 we will add intradermal (ID) autologous αDC1 vaccines (known to be nontoxic) to the tolerable IPC-CKM regimen. The effectiveness will be determined by rate of complete pathologic response.


Condition or disease Intervention/treatment Phase
Cancer of Ovary Cancer of the Ovary Neoplasms, Ovarian Ovarian Cancer Ovary Cancer Ovary Neoplasms Biological: Cisplatin + celecoxib + DC vaccine Biological: Cisplatin + CKM + Celecoxib + DC Vaccine Phase 1 Phase 2

Detailed Description:
On Phase 1, patients received up to 6 cycles of IPC, with CKM after the 2nd to 6th cycles. On Phase 2, patients will receive up to 6 -8 cycles of chemotherapy with ID injections of DC1 vaccine with CKM. To optimize the pattern of immunity, all patients will also receive oral celecoxib (COX2 inhibitor).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 4, 2015
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : June 1, 2026


Arm Intervention/treatment
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
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

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
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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Change in the number of CD3+CD8+ T cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  2. Change in the number of effector CD8+ T cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  3. Change in the number of CD4+ T cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  4. Change in the number of Tregs in the peritoneal fluid. [ Time Frame: 8 weeks ]
  5. Change in the number of myeloid-derived suppressor cells in the peritoneal fluid. [ Time Frame: 8 weeks ]

Other Outcome Measures:
  1. Change in the number of TH1 cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  2. Change in the number of natural killer cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  3. Change in the number of dendritic cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  4. Change in the number of activated macrophages in the peritoneal fluid. [ Time Frame: 8 weeks ]
  5. Change in the number of tumor cells in the peritoneal fluid. [ Time Frame: 8 weeks ]
  6. Change in the concentration of CCL3 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  7. Change in the concentration of CCL4 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  8. Change in the concentration of CCL5 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  9. Change in the concentration of CXCL9 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  10. Change in the concentration of CXCL10 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  11. Change in the concentration of CXCL11 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  12. Change in the concentration of CXCL12 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  13. Change in the concentration of GrB in the peritoneal fluid. [ Time Frame: 8 weeks ]
  14. Change in the concentration of IFN gamma in the peritoneal fluid. [ Time Frame: 8 weeks ]
  15. Change in the concentration of FoxP3 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  16. Change in the concentration of IDO in the peritoneal fluid. [ Time Frame: 8 weeks ]
  17. Change in the concentration of NO in the peritoneal fluid. [ Time Frame: 8 weeks ]
  18. Change in the concentration of IL-10 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  19. Change in the concentration of COX-2 in the peritoneal fluid. [ Time Frame: 8 weeks ]
  20. Change in the number of CD3+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  21. Change in the number of CD4+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  22. Change in the number of CD8+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  23. Change in the number of CD11b+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  24. Change in the number of CD11c+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  25. Change in the number of GrB+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  26. Change in the number of FoxP3+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  27. Change in the number of IDO+ cells in the tumor tissue. [ Time Frame: 8 weeks ]
  28. Change in the number of CCL3 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  29. Change in the number of CCL4 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  30. Change in the number of CCL5 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  31. Change in the number of CXCL9 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  32. Change in the number of CXCL10 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  33. Change in the number of CXCL11 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  34. Change in the number of CCL22 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  35. Change in the number of CXCL12 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  36. Change in the number of GrB cells in the tumor tissue. [ Time Frame: 8 weeks ]
  37. Change in the number of IFN gamma cells in the tumor tissue. [ Time Frame: 8 weeks ]
  38. Change in the number of FoxP3 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  39. Change in the number of IDO cells in the tumor tissue. [ Time Frame: 8 weeks ]
  40. Change in the number of NO cells in the tumor tissue. [ Time Frame: 8 weeks ]
  41. Change in the number of IL-10 cells in the tumor tissue. [ Time Frame: 8 weeks ]
  42. Change in the number of COX-2 cells in the tumor tissue. [ Time Frame: 8 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Patients must have advanced stage (III-IV) epithelial carcinoma 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 biopsy will be reviewed by our study pathologist at Magee.
    • Patients must be receiving neoadjuvant chemotherapy
  • Patients must be eligible for cancer-related definitive therapy with neoadjuvant chemotherapy
  • Patients must be chemonaive and receiving therapy in primary first line neoadjuvant setting
  • Patients must have GOG performance of 0-1
  • Patients must be reasonable candidates for interval debulking surgery as well as IP platinum based combination chemotherapy regimen with no prior evidence of clinically significant intra-abdominal adhesions, persistent abdominal wall infections, renal toxicity, or bowel obstruction.
  • 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 must be willing to undergo leukapheresis
  • Patients must agree to appropriate clinical monitoring to receive the study regimens.
  • Patient must have:

    • 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 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 or taxane chemotherapy. Patients with carboplatin allergy may be included if they tolerate a test dose of IV cisplatin given in monitored floor conditions. Patients who are allergic to paclitaxel, can be alternatively treated with abraxane.
  • 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.

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): NCT02432378


Locations
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United States, Pennsylvania
UPMC CancerCenter at Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, United States, 15213
Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Roswell Park Cancer Institute
AIM ImmunoTech Inc.
National Cancer Institute (NCI)
University of Pittsburgh
Investigators
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Principal Investigator: Robert P Edwards, MD University of Pittsburgh
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT02432378    
Other Study ID Numbers: 11-128
5P01CA132714 ( U.S. NIH Grant/Contract )
First Posted: May 4, 2015    Key Record Dates
Last Update Posted: October 19, 2022
Last Verified: October 2022
Additional relevant MeSH terms:
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Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Celecoxib
Cisplatin
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors