| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Primary stage IV high-grade serous ovarian, peritoneal, or fallopian tube cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10070908 |
| E.1.2 | Term | Ovarian cancer stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| to determine the immune-activating capacity of treatment with pembrolizumab and carboplatin/paclitaxel in the neo-adjuvant setting of primary stage IV ovarian cancer as measured by the alteration in magnitude and breadth of the tumor specific T cell response during therapy in peripheral blood. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the safety of the carboplatin-paclitaxel-pembrolizumab treatment
- To evaluate the tolerability of the carboplatin-paclitaxel-pembrolizumab treatment based on adverse events according to CTCAE version 4.03
- To assess the tumor response based on RECIST 1.1 and serum CA-125 levels
- To assess the efficacy of the treatment based on the result of the debulking surgery (no viable invasive tumor left in the resection specimen)
- To evaluate the feasibility of the carboplatin-paclitaxel-pembrolizumab treatment
- To evaluate Overall survival (OS, time from start chemotherapy to death from any cause)
- To evaluate Disease free Survival (DFS, time from start chemotherapy to tumor progression)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Have given written informed consent for the trial.
2. Have a histologically proven diagnosis of primary high-grade serous ovarian, peritoneal, or fallopian tube cancer. Stage IV disease should ideally be cytologically or histologically proven.
3. Be equal or more then 18 years of age on day of signing informed consent.
4. Be willing and able to provide three tumor biopsies (1 FFPE, 2 fresh frozen) prior to start of treatment in which the tumor’s immunogenic mutational load can be determined by DNA and RNA sequencing.
5. Have a performance status of 0 or 1 on the ECOG Performance Scale.
6. Demonstrate adequate organ function as defined in the protocol
7. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to first cycle of treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
|
|
| E.4 | Principal exclusion criteria |
1. Has previously received treatment for ovarian, peritoneal, or fallopian tube cancer.
1a 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.
1b 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.
2. Has a 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.
3. 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.
4. 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.
5. Has a known history of active TB (Bacillus Tuberculosis)
6. Hypersensitivity to pembrolizumab or any of its excipients.
7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
8. 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
9. Has known history of, or any evidence of active, non-infectious pneumonitis.
10. Has an active infection requiring systemic therapy.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| to determine the immune-activating capacity of treatment with pembrolizumab and carboplatin/paclitaxel in the neo-adjuvant setting of primary stage IV ovarian cancer as measured by the alteration in magnitude and breadth of the tumor specific T cell response during therapy in peripheral blood. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Prior to start treatment, before first en second cycle carboplatin/paclitaxel/pembrolizumab, before start pembrolizumab monotherapy, at end of treatment |
|
| E.5.2 | Secondary end point(s) |
- To evaluate the safety of the carboplatin-paclitaxel-pembrolizumab treatment
- To evaluate the tolerability of the carboplatin-paclitaxel-pembrolizumab treatment based on adverse events according to CTCAE version 4.03
- To assess the tumor response based on RECIST 1.1 and serum CA-125 levels
- To assess the efficacy of the treatment based on the result of the debulking surgery (no viable invasive tumor left in the resection specimen)
- To evaluate the feasibility of the carboplatin-paclitaxel-pembrolizumab treatment
- To evaluate Overall survival (OS, time from start chemotherapy to death from any cause)
- To evaluate Disease free Survival (DFS, time from start chemotherapy to tumor progression)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Safety/adverse events to be assessed after every cycle
- Response/efficay after 2 cycles chemotherapy and at surgery (pathology report)
- OS and DFS; follow up after treatment every 3 months until death |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
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