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Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03126812
Recruitment Status : Recruiting
First Posted : April 24, 2017
Last Update Posted : January 22, 2021
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief Summary:
This is a single arm feasibility study in patients with primary FIGO stage IV serous ovarian, peritoneal, or fallopian tube cancer to evaluate neo-adjuvant + adjuvant pembrolizumab for its capacity to induce and broaden T cell responses against tumor neo-antigens.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Stage IV Peritoneal Cancer Fallopian Tube Cancer Drug: Carboplatin Drug: Paclitaxel Drug: Pembrolizumab Phase 1 Phase 2

Detailed Description:

Long-term survival in stage IV serous ovarian, peritoneal, and fallopian tube cancer is poor and has not significantly improved over the last decades. Standard treatment consists of debulking surgery and six courses of carboplatin and paclitaxel. Nevertheless, the disease recurs in >90% of women, usually within two years.

Since early observations that the presence of infiltrating T cells is associated with improved outcome, ovarian cancer is linked to a potential benefit of immunotherapy.10 More recently, T cell checkpoint blockade with anti-PD1 and anti-PDL1 have shown promising activity in platinum resistant ovarian cancer with objective and durable responses in 10-20% of patients. This finding raises the question whether anti-PD1 could also play a role in first line treatment of ovarian cancer.

To fully use the power of T cell checkpoint inhibition, sufficient TCR stimulation is required. Importantly, the amount of antigen that can provide this signal will correlate with tumor load, and because of this adjuvant immunotherapy may work most efficiently, when initiated prior to surgery. In addition, we postulate that antigen retrieval will increase after induction treatment with cytotoxic therapy.

To address these questions, we propose a feasibility study in patients with FIGO stage IV serous ovarian, peritoneal, or fallopian tube cancer in which we evaluate pembrolizumab added to standard treatment for its capacity to induce and broaden T cell responses against neo-antigens.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Feasibility Study of Neo-adjuvant Treatment With Carboplatin, Paclitaxel and Pembrolizumab in Primary Stage IV Serous Ovarian Cancer
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2025

Arm Intervention/treatment
Experimental: Carboplatin, paclitaxel, pembrolizumab
Carboplatin AUC= 6 paclitaxel 80 mg/m2 Pembrolizumab 200 mg starting cycle 2
Drug: Carboplatin
Carboplatin AUC=6

Drug: Paclitaxel
paclitaxel 80 mg/m2

Drug: Pembrolizumab
200 mg flat dose, starting cycle 2

Primary Outcome Measures :
  1. Number of T-cells in peripheral blood [ Time Frame: up to week 52 ]
    determine the number of T cells in peripheral blood samples and tissue samples

Secondary Outcome Measures :
  1. Toxicity; Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0 [ Time Frame: up to 30 days after end of treatment ]
    Toxicity will be analyzed in patients who have received at least one administration of pembrolizumab.

  2. Response Rate [ Time Frame: at week 12, debulking surgery ]
    number of patients with no viable invasive tumor left in the resection specimen

  3. Response rate according to RECIST [ Time Frame: at week 3 and 6 ]
    Number of patients with partial or complete response according to RECIST

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Written informed consent for the trial.
  • Diagnosis of primary stage IV high-grade serous ovarian, peritoneal, or fallopian tube cancer.
  • Age >= 18 years on day of signing informed consent.
  • Willing and able to provide three tumor biopsies (1 FFPE, 2 fresh frozen) prior to start of treatment
  • Performance status of 0 or 1 on the ECOG Performance Scale.
  • Adequate organ function as defined in Table 1 of the protocol
  • 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. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Exclusion Criteria:

  • Previously received treatment for ovarian, peritoneal, or fallopian tube cancer.

    • 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.
  • Known additional malignancy, unless treated with curative intent without chemotherapy at least five years ago. In situ cancers, basal cell carcinoma of the skin or squamous cell carcinoma of the skin that have undergone potentially curative therapy within the past five years may also be eligible.
  • 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.
  • 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.
  • 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

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 identifier (NCT number): NCT03126812

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Contact: Gabe Sonke, MD +3120512 ext 9111
Contact: Ingrid Mandjes, MSc

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Antoni van Leeuwenhoek Recruiting
Amsterdam, Netherlands
Contact: G Sonke, MD   
Contact: L Aronson   
Principal Investigator: G Sonke, MD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Merck Sharp & Dohme Corp.
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Responsible Party: The Netherlands Cancer Institute Identifier: NCT03126812    
Other Study ID Numbers: N16OPE
First Posted: April 24, 2017    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: to be determinated

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The Netherlands Cancer Institute:
Primary stage 4
Neo adjuvant
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological