Clinical trial NCT02432378: Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines
Official title: A PHASE 2 EFFICACY TRIAL OF INTENSIVE LOCOREGIONAL CHEMOIMMUNOTHERAPY FOR ADVANCED STAGE OVARIAN CANCER AND TUMOR-SPECIFIC INTRANODAL AUTOLOGOUS ALPHA-DC1 VACCINES
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Cancer of Ovary
Cancer of the Ovary
Neoplasms, Ovarian
Ovarian Cancer
Ovary Cancer
Ovary Neoplasms
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: AIM ImmunoTech Inc.
name: National Cancer Institute (NCI)
name: University of Pittsburgh
First posted: 2015-05-04
Enrollment: 25
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: On Phase 1, patients received up to 6 cycles of IPC, with CKM after the 2nd to 6th cycles. On Phase 2, (which opened 8/27/24/ )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).

Eligibility 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.

Primary outcomes:
measure: Change in the number of CD8+ tumor infiltrating T cells in the peritoneal fluid.
timeFrame: 8 weeks
measure: Number of adverse events for the different combinations
timeFrame: 8 weeks
Secondary outcomes:
measure: Change in the number of CD3+CD8+ T cells in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the number of effector CD8+ T cells in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the number of CD4+ T cells in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the number of Tregs in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the number of myeloid-derived suppressor cells in the peritoneal fluid.
timeFrame: 8 weeks
Other outcomes:
measure: Change in the number of TH1 cells in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the number of natural killer cells in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the number of dendritic cells in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the number of activated macrophages in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the number of tumor cells in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of CCL3 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of CCL4 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of CCL5 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of CXCL9 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of CXCL10 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of CXCL11 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of CXCL12 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of GrB in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of IFN gamma in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of FoxP3 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of IDO in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of NO in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of IL-10 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the concentration of COX-2 in the peritoneal fluid.
timeFrame: 8 weeks
measure: Change in the number of CD3+ cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CD4+ cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CD8+ cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CD11b+ cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CD11c+ cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of GrB+ cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of FoxP3+ cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of IDO+ cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CCL3 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CCL4 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CCL5 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CXCL9 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CXCL10 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CXCL11 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CCL22 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of CXCL12 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of GrB cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of IFN gamma cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of FoxP3 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of IDO cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of NO cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of IL-10 cells in the tumor tissue.
timeFrame: 8 weeks
measure: Change in the number of COX-2 cells in the tumor tissue.
timeFrame: 8 weeks
Locations:
city: Pittsburgh
country: United States
facility: UPMC CancerCenter at Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hillman Cancer Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Robert P Edwards, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Orr B, Mahdi H, Fang Y, Strange M, Uygun I, Rana M, Zhang L, Suarez Mora A, Pusateri A, Elishaev E, Kang C, Tseng G, Gooding W, Edwards RP, Kalinski P, Vlad AM. Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity. Clin Cancer Res. 2022 May 13;28(10):2038-2049. doi: 10.1158/1078-0432.CCR-21-3659.