Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT03126812
• Recruitment Status: Recruiting
• First Posted: April 24, 2017
• Last Update Posted: January 22, 2021
• Sponsor: The Netherlands Cancer Institute
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): The Netherlands Cancer Institute

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Gabe Sonke, MD; +3120512 ext 9111; g.sonke@nki.nl

Contact: Ingrid Mandjes, MSc; i.mandjes@nki.nl

Locations

Netherlands

Antoni van Leeuwenhoek; Recruiting

Amsterdam, Netherlands

Contact: G Sonke, MD g.sonke@nki.nl

Contact: L Aronson l.aronson@nki.nl

Principal Investigator: G Sonke, MD

Sponsors and Collaborators

The Netherlands Cancer Institute

Merck Sharp & Dohme Corp.

More Information

• Responsible Party: The Netherlands Cancer Institute
• ClinicalTrials.gov Identifier: NCT03126812
• Other Study ID Numbers: N16OPE
• First Posted: April 24, 2017
• 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

• 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:

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