The primary objective of this study is 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…
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective: The primary objective of this study is 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.
Secondary outcome
Secondary objectives of this study are:
- 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)
Background summary
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 objective
The primary objective of this study is 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.
Study design
- Three cycles carboplatin/paclitaxel. Pembrolizumab will be added from cycle 2.
- Debulking surgery (standard)
- Three cycles carboplatin/paclitaxel/pembrolizumab
- 7 cycles mono therapy pembrolizumab
Protocol version 2.1 dated 15 January2020:
Patients with germline or somatic BRCA1 / 2 mutations will be treated with
PARPi according to the local guideline when indicated. This oral therapy is
added to the standard treatment, and therefore also to the current study
protocol.
Study burden and risks
The patient may experience additional side effects from the addition of
pembrolizumab to the standard chemotherapy schedule.
The patient may also experience physical discomfort with some of the procedures
performed during the study such as blood sampling, the IV line en tumor biopsy.
Plesmanlaan 121
Amsterdam 1066CX
NL
Plesmanlaan 121
Amsterdam 1066CX
NL
Listed location countries
Inclusion criteria
1. Written informed consent for the trial.
2. Diagnosis of primary high-grade serous ovarian, peritoneal, or fallopian
tube cancer. Stage IV disease should ideally be cytologically or histologically
proven
3. Age >= 18 years on day of signing informed consent.
4. Willing and able to provide three tumor biopsies (1 FFPE, 2 fresh frozen)
prior to start of treatment
5. Performance status of 0 or 1 on the ECOG Performance Scale.
6. Adequate organ function as defined in Table 1 of the protocol
7. 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
1. previously received treatment for ovarian, peritoneal, or fallopian tube
cancer.
2. 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. 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. 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. A known history of active TB (Bacillus Tuberculosis)
6. Hypersensitivity to pembrolizumab or any of its excipients.
7. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior
to study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004700-56-NL |
| ClinicalTrials.gov | NCT03126812 |
| CCMO | NL59444.031.16 |