Back to results

Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer

Primary Purpose

Ovarian Cancer Stage IV, Peritoneal Cancer, Fallopian Tube Cancer

Status

Recruiting

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

Carboplatin

Paclitaxel

Pembrolizumab

About this trial

This is an interventional treatment trial for Ovarian Cancer Stage IV focused on measuring Primary stage 4, Neo adjuvant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Antoni van LeeuwenhoekRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Carboplatin, paclitaxel, pembrolizumab

Arm Description

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

Outcomes

Primary Outcome Measures

Number of T-cells in peripheral blood

determine the number of T cells in peripheral blood samples and tissue samples

Secondary Outcome Measures

Toxicity; Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0

Toxicity will be analyzed in patients who have received at least one administration of pembrolizumab.

Response Rate

number of patients with no viable invasive tumor left in the resection specimen

Response rate according to RECIST

Number of patients with partial or complete response according to RECIST

Full Information

NCT ID

NCT03126812

First Posted

December 19, 2016

Last Updated

March 21, 2022

Sponsor

The Netherlands Cancer Institute

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03126812

Brief Title

Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer

Official Title

Feasibility Study of Neo-adjuvant Treatment With Carboplatin, Paclitaxel and Pembrolizumab in Primary Stage IV Serous Ovarian Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 1, 2017 (Actual)

Primary Completion Date

June 2023 (Anticipated)

Study Completion Date

June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The Netherlands Cancer Institute

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ovarian Cancer Stage IV, Peritoneal Cancer, Fallopian Tube Cancer

Keywords

Primary stage 4, Neo adjuvant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Carboplatin, paclitaxel, pembrolizumab

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

Carboplatin AUC=6

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Intervention Description

paclitaxel 80 mg/m2

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Intervention Description

200 mg flat dose, starting cycle 2

Primary Outcome Measure Information:

Title

Number of T-cells in peripheral blood

Description

determine the number of T cells in peripheral blood samples and tissue samples

Time Frame

up to week 52

Secondary Outcome Measure Information:

Title

Toxicity; Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0

Description

Toxicity will be analyzed in patients who have received at least one administration of pembrolizumab.

Time Frame

up to 30 days after end of treatment

Title

Response Rate

Description

number of patients with no viable invasive tumor left in the resection specimen

Time Frame

at week 12, debulking surgery

Title

Response rate according to RECIST

Description

Number of patients with partial or complete response according to RECIST

Time Frame

at week 3 and 6

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Gabe Sonke, MD

Phone

+3120512

Ext

9111

g.sonke@nki.nl

First Name & Middle Initial & Last Name or Official Title & Degree

Ingrid Mandjes, MSc

i.mandjes@nki.nl

Facility Information:

Facility Name

Antoni van Leeuwenhoek

City

Amsterdam

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

G Sonke, MD

g.sonke@nki.nl

First Name & Middle Initial & Last Name & Degree

L Aronson

l.aronson@nki.nl

First Name & Middle Initial & Last Name & Degree

G Sonke, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

to be determinated

Learn more about this trial

Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer

We'll reach out to this number within 24 hrs