Ovarian Cancer Stage IVPhase 1/2NCT03126812
Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer
A Phase 1/2 study testing Carboplatin, Paclitaxel and Pembrolizumab in people with Ovarian Cancer Stage IV and Peritoneal Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer Stage IV, Peritoneal Cancer, Fallopian Tube Cancer
- What is being tested?
- Carboplatin, Paclitaxel and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Nov 2017to 5 Mar 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Feasibility Study of Neo-adjuvant Treatment With Carboplatin, Paclitaxel and Pembrolizumab in Primary Stage IV Serous Ovarian Cancer
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.
Read the 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.
- Being tested
- Carboplatin, Paclitaxel, Pembrolizumab
- Keywords
- Primary stage 4, Neo adjuvant
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Carboplatin AUC=6
PaclitaxelDrug
paclitaxel 80 mg/m2
PembrolizumabDrug
200 mg flat dose, starting cycle 2
| Study group | Role | What they receive |
|---|---|---|
| Carboplatin, paclitaxel, pembrolizumab | Experimental | Carboplatin AUC= 6 paclitaxel 80 mg/m2 Pembrolizumab 200 mg starting cycle 2 Receives: Drug: Carboplatin; Drug: Paclitaxel; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of T-cells in peripheral blood
determine the number of T cells in peripheral blood samples and tissue samples
Measured: up to week 52
Secondary outcomes (3)
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.
Measured: up to 30 days after end of treatment
Response Rate
number of patients with no viable invasive tumor left in the resection specimen
Measured: at week 12, debulking surgery
Response rate according to RECIST
Number of patients with partial or complete response according to RECIST
Measured: at week 3 and 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2017
- Study start1 Nov 2017
- Primary completion1 Jun 2023
- Study completion5 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian Cancer Stage IVStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03126812
- Sponsor's protocol ID
- N16OPE
- Status last verified
- May 2024
- First submitted
- 19 Dec 2016
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: to be determinated
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility Study of Neo-adjuvant Treatment With Carboplatin, Paclitaxel and Pembrolizumab in Primary Stage IV Serous Ovarian Cancer
- ClinicalTrials.gov ID
- NCT03126812
- Acronym / sponsor ID
- N16OPE
- Keywords
- Primary stage 4, Neo adjuvant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 5 Mar 2024 (actual)
- First posted
- 24 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carboplatin, paclitaxel, pembrolizumab | Experimental | Drug: Carboplatin, Drug: Paclitaxel, Drug: PembrolizumabCarboplatin AUC= 6 paclitaxel 80 mg/m2 Pembrolizumab 200 mg starting cycle 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- Previously received treatment for ovarian, peritoneal, or fallopian tube cancer.
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarboplatinCarboplatin AUC=6 | Drug | Carboplatin, paclitaxel, pembrolizumab |
| Paclitaxelpaclitaxel 80 mg/m2 | Drug | Carboplatin, paclitaxel, pembrolizumab |
| Pembrolizumab200 mg flat dose, starting cycle 2 | Drug | Carboplatin, paclitaxel, pembrolizumab |
Primary outcome
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
3 secondary outcomes
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
Response Rate
Time frame: at week 12, debulking surgery
Response rate according to RECIST
Time frame: at week 3 and 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
- Individual participant dataSharing planned: Undecided. to be determinated
Related trials for Ovarian Cancer Stage IV
RecruitingPhase 2
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Cancer
Metastatic Colorectal Cancer, Metastatic Pancreatic Cancer
Active, not recruitingPhase 2
Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Active, not recruiting
e-Health Intervention (Day-by-Day) for the Management of Fear of Progression in Women With Stage III or IV Gynecologic Cancer: A Pilot Study
Malignant Female Reproductive System Neoplasm, Stage III Cervical Cancer AJCC v8
RecruitingPhase 3
Mo-Rez in First- Line (1L) Maintenance Treatment of Non-Homologous Recombination Deficient Ovarian Cancer (Non-HRd OC) [BEHOLD-Ovarian03]
Ovarian Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Carboplatin, Paclitaxel and Pembrolizumab in people with Ovarian Cancer Stage IV and Peritoneal Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of T-cells in peripheral blood (time frame: up to week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2024.