NCT02432378

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Sep 2015

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 8, 2015

Completed
26 days until next milestone

First Posted

Study publicly available on registry

May 4, 2015

Completed
4 months until next milestone

Study Start

First participant enrolled

September 4, 2015

Completed
9.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 19, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 19, 2025

Completed
Last Updated

June 19, 2025

Status Verified

June 1, 2025

Enrollment Period

9.8 years

First QC Date

April 8, 2015

Last Update Submit

June 18, 2025

Conditions

Cancer of OvaryCancer of the OvaryNeoplasms, OvarianOvarian CancerOvary CancerOvary Neoplasms

Outcome Measures

Primary Outcomes (2)

  • Change in the number of CD8+ tumor infiltrating T cells in the peritoneal fluid.

    The difference in CD8+ tumor infiltrating T cells over 3 cycles of platinum based chemotherapy plus immunotherapy compared with baseline.

    8 weeks

  • Number of adverse events for the different combinations

    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.

    8 weeks

Secondary Outcomes (5)

  • Change in the number of CD3+CD8+ T cells in the peritoneal fluid.

    8 weeks

  • Change in the number of effector CD8+ T cells in the peritoneal fluid.

    8 weeks

  • Change in the number of CD4+ T cells in the peritoneal fluid.

    8 weeks

  • Change in the number of Tregs in the peritoneal fluid.

    8 weeks

  • Change in the number of myeloid-derived suppressor cells in the peritoneal fluid.

    8 weeks

Other Outcomes (42)

  • Change in the number of TH1 cells in the peritoneal fluid.

    8 weeks

  • Change in the number of natural killer cells in the peritoneal fluid.

    8 weeks

  • Change in the number of dendritic cells in the peritoneal fluid.

    8 weeks

  • +39 more other outcomes

Study Arms (2)

Cisplatin + Celecoxib + DC Vaccine

EXPERIMENTAL

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 + CKM + Celecoxib + DC Vaccine

EXPERIMENTAL

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

Interventions

Cisplatin + celecoxib + DC vaccineBIOLOGICAL

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

Cisplatin + Celecoxib + DC Vaccine
Cisplatin + CKM + Celecoxib + DC VaccineBIOLOGICAL

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

Cisplatin + CKM + Celecoxib + DC Vaccine

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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;
  • +8 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

UPMC CancerCenter at Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

  • 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.

    PMID: 35046055DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

CisplatinCelecoxibCreatine Kinase, MM Form

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsBenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsPyrazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCreatine KinasePhosphotransferases (Nitrogenous Group Acceptor)PhosphotransferasesTransferasesEnzymesEnzymes and Coenzymes

Study Officials

  • Robert P Edwards, MD

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 8, 2015

First Posted

May 4, 2015

Study Start

September 4, 2015

Primary Completion

June 19, 2025

Study Completion

June 19, 2025

Last Updated

June 19, 2025

Record last verified: 2025-06

Locations

US(2)