Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer

NCT ID: NCT03126812

Last Updated: 2024-05-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-01
• Study Completion Date: 2024-03-05

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.

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.

Conditions

Ovarian Cancer Stage IV; Peritoneal Cancer; Fallopian Tube Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carboplatin, paclitaxel, pembrolizumab

Carboplatin AUC= 6 paclitaxel 80 mg/m2 Pembrolizumab 200 mg starting cycle 2

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Carboplatin AUC=6

Paclitaxel

Intervention Type: DRUG

paclitaxel 80 mg/m2

Pembrolizumab

Intervention Type: DRUG

200 mg flat dose, starting cycle 2

Interventions

Carboplatin

Carboplatin AUC=6

Intervention Type: DRUG

Paclitaxel

paclitaxel 80 mg/m2

Intervention Type: DRUG

Pembrolizumab

200 mg flat dose, starting cycle 2

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Countries

Netherlands

Other Identifiers

N16OPE

Identifier Type: -

Identifier Source: org_study_id