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Phase II: Pembrolizumab/Carboplatin/Taxol in Epithelial Ovary Cancer

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ClinicalTrials.gov Identifier: NCT02766582
Recruitment Status : Recruiting
First Posted : May 10, 2016
Last Update Posted : October 22, 2018
Sponsor:
Collaborator:
The Cleveland Clinic
Information provided by (Responsible Party):
Denise Uyar, Medical College of Wisconsin

Brief Summary:
Phase II single arm, open label, nonrandomized study. The aim of our study is to assess the Progression Free Survival (PFS) in suboptimally cytoreduced epithelial ovarian/ primary peritoneal/ fallopian tube cancer patients treated with the novel combination of carboplatin every 21 days (triweekly) /weekly paclitaxel IV with pembrolizumab IV followed by maintenance pembrolizumab IV.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Pembrolizumab Drug: Carboplatin Drug: Paclitaxel Phase 2

Detailed Description:
Utilization of combination standard intravenous chemotherapy with intravenous pembrolizumab (for 6 cycles) in first line treatment of patients with advanced ovarian cancer post surgery with any residual disease. This will be followed by single agent intravenous pembrolizumab (every 3 weeks) for 12 additional cycles.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Open Label Nonrandomized Trial of the Anti PD 1 Therapy Pembrolizumab With First Line Platinum Based Chemotherapy Followed by 12 Months Pembrolizumab Monotherapy for Patients With Stage III/IV Epithelial Ovarian Cancer
Study Start Date : October 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Chemotherapy combined with pembrolizumab

Single arm study:

Pembrolizumab IV every 21 days (200 mg) Carboplatin IV every 21 days Paclitaxel IV infusion (80 mg/m2) every 7 days for 6 cycles Followed by 12 months pembrolizumab IV every 21 days

Drug: Pembrolizumab
IV every 21 days at 200 mg
Other Name: Keytruda

Drug: Carboplatin
IV every 21 days
Other Name: Paraplatin

Drug: Paclitaxel
IV infusion (80mg/m2) every 7 days for 6 cycles
Other Names:
  • Taxol
  • Onxol




Primary Outcome Measures :
  1. Progression Free Survival (PFS) of combination platinum based therapy with anti-Programmed Death (PD)-1 therapy followed by maintenance anti-PD-1 therapy in patients with epithelial ovarian cancer (EOC). [ Time Frame: 24-48 months ]
    Time to progression free survival (PFS) is the period from study entry (first dose of therapy) until disease progression, death or date of last contact.


Secondary Outcome Measures :
  1. Overall Survival (OS) of combination platinum based therapy with anti-PD-1 therapy followed by maintenance anti-PD-1 therapy in patient with suboptimally cytoreduced epithelial ovarian cancer. [ Time Frame: 24-48 months ]
    Overall survival (OS) will be defined as observed length of life from entry into the protocol (first dose of therapy) to death, or for living patients, date of last contact (regardless of whether or not this contact is on a subsequent protocol.

  2. Monitor quality of life during combination therapy and single agent maintenance therapy with anti-PD-1 therapy with the Functional Assessment of Cancer Therapy (FACT) surveys at intervals during therapy. [ Time Frame: Every 6 months during treatment until 6 months after completion of therapy. 24-28 months ]
    Each cycle is 21 days.


Other Outcome Measures:
  1. PD-L1 expression in preserved tissue obtained at the time of initial diagnosis for patients [ Time Frame: At enrollment tissue from cytoreductive surgery will be obtained from pthology blocks. ]
    PD-L1 expression in preserved tissue obtained at the time of initial diagnosis for patients with suboptimally cytoreduced ovarian cancer using immunohistochemistry (IHC) of initial tumor samples and correlate with clinical outcomes of response and survival.

  2. CD4 lymphocyte subset panel at discrete time intervals during therapy and after therapy completion [ Time Frame: At screening, within one week of initiating cycle 7 of maintenance, 30 days post discontinuation and at the time of recurrence. 36- 48 months. ]
    The investigators will utilize multiparametric flow cytometry of CD4 leukocyte subsets from patient samples to augment understanding of the human immune system undergoing combination chemotherapy and immunotherapy. Each cycle is 21 days.

  3. CD8 lymphocyte subset panel at discrete time intervals during therapy and after therapy completion [ Time Frame: At screening, within one week of initiating cycle 7 of maintenance and 30 days post discontinuation at at the time of recurrence. 36- 48 months. ]
    The investigators will utilize multiparametric flow cytometry of CD8 leukocyte subsets from patient samples to augment understanding of the human immune system undergoing combination chemotherapy and immunotherapy. Each cycle is 21 days.

  4. B-Cell lymphocyte subset panel at discrete time intervals during therapy and after therapy completion. [ Time Frame: At screening, within one week of initiating cycle 7 of maintenance and 30 days post discontinuation at at the time of recurrence. 36 -48 months. ]
    The investigators will utilize multiparametric flow cytometry of B-cell leukocyte subsets from patient samples to augment understanding of the human immune system undergoing combination chemotherapy and immunotherapy. each cycle is 21 days.

  5. T-cell lymphocyte subset panel at discrete time intervals during therapy and after therapy completion. [ Time Frame: At screening, within one week of initiating cycle 7 of maintenance and 30 days post discontinuation at at the time of recurrence. 36 -48 months. ]
    The investigators will utilize multiparametric flow cytometry of T-cell leukocyte subsets from patient samples to augment the understanding of the human immune system undergoing combination chemotherapy and immunotherapy. each cycle is 21 days.

  6. Natural Killer Cell lymphocyte subset panel at discrete time intervals during therapy and after therapy completion. [ Time Frame: At screening, within one week of initiating cycle 7 of maintenance and 30 days post discontinuation at at the time of recurrence. 36 -48 months. ]
    The investigators will utilize multiparametric flow cytometry of Natural Killer Cell leukocyte subsets from patient samples to augment the understanding of the human immune system undergoing combination chemotherapy and immunotherapy. Each cycle is 21 days.



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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:

  • Have advance stage III/IV epithelial ovarian, fallopian tube or primary peritoneal cancer
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be 18 years of age or older on day of signing informed consent.
  • Suboptimal cytoreductive surgery defined as any residual disease noted per operative report and/or have measurable/macroscopic disease (defined as target and/or non-target lesions) based on RECIST 1.1.
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
  • Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.
  • Demonstrate adequate organ function
  • All screening labs should be performed within 28 days of treatment initiation.
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication.
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.

Exclusion Criteria:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has a known additional malignancy within the last 3 years, or that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study. The investigator should consult the Study Chair.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Patients with borderline ovarian tumors, recurrent epithelial ovarian/ primary peritoneal cancer/fallopian tube cancer or non-epithelial ovarian cancer are not eligible.
  • Has received a live vaccine within 30 days of planned start of study 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): NCT02766582


Contacts
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Contact: Denise Uyar, MD 414-805-6634 duyar@mcw.edu

Locations
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United States, Wisconsin
Medical College of Wisconsin and Froedtert Hospital Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Denise Uyar, MD    414-805-6606    duyar@mcw.edu   
Contact: Suki Skandarajah, B.Sc    414-805-5337    sskandarajah@mcw.edu   
Sponsors and Collaborators
Medical College of Wisconsin
The Cleveland Clinic
Investigators
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Principal Investigator: Denise Uyar, MD Medical College of Wisconsin

Publications:

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Responsible Party: Denise Uyar, Associate Professor; Chief of Gynecologic Oncology, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT02766582     History of Changes
Other Study ID Numbers: Uyar 25680 IIT Merck
First Posted: May 10, 2016    Key Record Dates
Last Update Posted: October 22, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Denise Uyar, Medical College of Wisconsin:
Ovarian
platinum
pembrolizumab
taxane

Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Carboplatin
Pembrolizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological