This study has been transitioned to CTIS with ID 2023-506177-35-00 check the CTIS register for the current data. Objective: To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab,…
ID
Source
Brief title
Condition
- Ovarian and fallopian tube disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary: To compare pembrolizumab plus paclitaxel with or without bevacizumab
to placebo plus paclitaxel with or without bevacizumab, with
respect to progression-free survival (PFS) per RECIST 1.1 as assessed by the
investigator
Secondary outcome
Secondary:
- To compare pembrolizumab plus paclitaxel with or without bevacizumab to
placebo plus paclitaxel with or without bevacizumab, with
respect to overall survival (OS)
- To compare pembrolizumab plus paclitaxel with or without bevacizumab to
placebo plus paclitaxel with or without bevacizumab, with respect to
progression free survival (PFS)
- To evaluate the safety and tolerability of pembrolizumab in combination with
paclitaxel with or without bevacizumab
- To compare pembrolizumab plus paclitaxel with or without bevacizumab to
placebo plus paclitaxel with or without bevacizumab, with respect to Global
Health Status/Quality of Life (GHS/QoL) score
Background summary
Ovariumcarcinoma (OC) is the 20th most common cancer, with an estimated 295,414
new cases diagnosed worldwide. OC is typically diagnosed in advanced stages.
The 5-year survival rate for patients with OC is only about 48%, and in
patients with distant disease only 29%. Given the high toxicity with the
current SOC chemotherapeutic regimens and no clear improvement in OS, there
remains an urgent requirement for novel therapies to be identified for women
with platinum-resistant disease. Due to over-expressed PD-LI in OC, the
combination of chemotherapy and immune checkpoint blockade may be a rational
approach for the treatment of recurrent OC.
Pembrolizumab is a potent humanized IgG4 monoclonal antibody (mAb) with high
specificity of binding to the programmed cell death 1 (PD-1) receptor, thus
inhibiting its interaction with ligand PD-L1 and ligand PD-L2. Based on
preclinical in vitro data, pembrolizumab has high affinity and potent receptor
blocking activity for PD-1. Pembrolizumab has an acceptable preclinical safety
profile and is in clinical development as an intravenous (IV) immunotherapy for
advanced malignancies. Keytruda® (pembrolizumab) is indicated for the treatment
of patients across a number of
indications.
The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to
suppress immune control. The normal function of PD-1, expressed on the cell
surface of activated T- cells under healthy conditions, is to down-modulate
unwanted or excessive immune responses, including autoimmune reactions. As a
consequence, the PD-1/PD-L1 pathway is an attractive target for therapeutic
intervention of recurrent OC
Study objective
This study has been transitioned to CTIS with ID 2023-506177-35-00 check the CTIS register for the current data.
Objective: To compare pembrolizumab plus paclitaxel with or without bevacizumab
to placebo plus paclitaxel with or without bevacizumab, with
respect to progression-free survival (PFS) per RECIST 1.1 as assessed by the
investigator.
Study design
This is an randomized, multicenter, double-blind, phase 3-study with
pembrolizumab (MK3475) plus paclitaxel versus placebo plus paclitaxel, with or
without bevacizumab for patient with Platinum-resistant Recurrent Ovarian
Cancer.
Approximately 616 participants will be randomly assigned (1:1) to 1 of 2
treatment arms. Screening procedures must be completed within 28 days prior to
treatment. Eligible participants are randomly assigned to Arm 1 or 2 to one fo
the following study intervention groups until one of the conditions for
discontinuation of study intervention is met.After the end-of-treatment, each
participant will be followed for the
occurrence of adverse events and spontaneously reported pregnancy.
The Sponsor estimates that the study will require approximately 65 months from
the time the first participant (or their legally acceptable representative)
provides documented informed consent until the last participant*s last
study-related contact.All participants will be followed for overall survival
until death, withdrawal of consent, or the end of the study.
Intervention
Arm 1:
Pembrolizumab 400 mg (Q6W, 18 cycles)
+
Paclitaxela 80 mg/m2 days 1, 8, 15 of each Q3W-cycle
(± bevacizumab 10 mg/kg Q2Wb)
Arm 2:
Placebo (Q6W, 18 cycles)
+
Paclitaxela 80 mg/m2 days 1, 8, 15 of each Q3W-cyclus
(± bevacizumab 10 mg/kg Q2Wb)
Study burden and risks
For this study, patients will be subjected to invasive procedures such as blood
collection, Biopsy (if applicable), CT-MRI or bone scans, physical exams,
possibly confrontational questionnaires, and patients will be asked to visit
the hospital regularly. Patients will be administered with different kinds of
medication present in the different interventiongroups during sixweek cycles up
to a maximum of 18 doses and 9 additional doses.
It cannot be guaranteed that participants in clinical studies will directly
benefit from study intervention during participation, as clinical studies are
designed to provide information about the safety and effectiveness of an
investigational medicine. Pembrolizumab has been administered in a large number
of cancer participants with a well characterized safety profile and has
received regulatory approval for multiple malignancies. Overall, pembrolizumab
is well tolerated at doses up to 10 mg/kg every 2 weeks (Q2W). Pembrolizumab
has also demonstrated anticancer clinical activity and efficacy in a broad
range of cancer indications.
Waarderweg 39
Haarlem 2031 BN
NL
Waarderweg 39
Haarlem 2031 BN
NL
Listed location countries
Age
Inclusion criteria
The below-mentioned inclusion criteria are the most important ones. A complete
list of cohort specific inclusion criteria can be found in the protocol.
1. Has histologically confirmed epithelial (including high-grade serous or
predominantly
serous, low-grade serous, any-grade endometrioid, malignant mixed Müllerian
tumors
[carcinosarcoma], or clear cell) ovarian, fallopian tube, or primary peritoneal
carcinoma.
2. Has received 1 or 2 prior lines of systemic therapy for OC, including at
least 1 prior
platinum-based therapy.
3. Has radiographic evidence of disease progression within 6 months (180 days)
after the
last dose of platinum-based chemotherapy for OC (ie, platinum-resistant
disease).
4. Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
5. Is female, and at least 18 years of age, at the time of signing the informed
consent.
6. Has an ECOG performance status of 0 to 1 assessed within 3 days before
randomization.
7. A female participant is eligible to participate if she is not pregnant or
breastfeeding
8. The participant (or legally acceptable representative) has provided
documented informed
consent for the study
9. Has radiographically evaluable disease
10. Archival tumor tissue sample or newly obtained core or
incisional/excisional biopsy of a
tumor lesion not previously irradiated has been provided
11. Have adequate organ function
Exclusion criteria
The below-mentioned exclusion criteria are the most important ones. A complete
list of cohort specific exclusion criteria can be found in the protocol.
1. Has nonepithelial cancers (germ cell tumors and sex cord-stromal tumors),
borderline
tumors (low malignant potential), mucinous, seromucinous that is predominantly
mucinous, malignant Brenner*s tumor and undifferentiated carcinoma.
2. Has primary platinum-refractory disease, defined as disease that has
progressed per
radiographic imaging while receiving or within 28 days of the last dose of
first-line platinum-based therapy.
3. Has prior disease progression on weekly paclitaxel alone.
4. Has uncontrolled hypertension. Note: only for patients receiving bevacizumab
5. Has current, clinically relevant bowel obstruction. Note: only for patients
receiving bevacizumab
6. Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active
gastrointestinal
bleeding within 6 months before randomization.Note: This applies only to
participants who will receive bevacizumab.
7. Has received >2 prior lines of systemic therapy for OC
8. Has received prior systemic anticancer therapy, including investigational
agents or maintanance therapy (including bevacizumab maintanance therapy) within
4 weeks before randomization
9. Has received prior radiation therapy within 2 weeks of start of study
intervention.
10. Has not recovered adequately from surgery and/or any complications from the
surgery.
11.Has received colony-stimulating factors within 4 weeks before randomization.
12. Has received a live or live-attenuated vaccine within 30 days before the
first dose of
study intervention
13. Has received an investigational agent or
has used an investigational device within 4 weeks prior to study intervention
administration.
14. Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy within 7 days before the first dose of study medication.
15. Has a known additional malignancy that is progressing or has required
active treatment
within the past 3 years.
16. Has known active CNS metastases and/or carcinomatous meningitis.
Participants with
previously treated brain metastases may participate provided they are
radiologically stable
17. Has severe hypersensitivity (>=Grade 3) to pembrolizumab, paclitaxel, or
bevacizumab
18. Has an active autoimmune disease that has required systemic treatment in
the past 2 years
19. Has a history of (noninfectious) pneumonitis/interstitial lung disease that
required
steroids or has current pneumonitis/interstitial lung disease.
20. Has an active infection requiring systemic therapy
21. Has a known history of HIV infection.
22. Has a known history of Hepatitis B or known active Hepatitis C virus
23. Has a history or current evidence of any condition, therapy, laboratory
abnormality, or other circumstance that might confound the results of the study
or interfere with the participant's participation for the full duration of the
study
24. Has a known psychiatric or substance abuse disorder that would interfere
with the participant's ability to cooperate with the requirements of the study.
25. Participant, in the judgement of the investigator, is unlikely to comply
with the study procedures, restrictions, and requirements of the study.
26. Has had an allogenic tissue/solid organ transplant
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 |
|---|---|
| EU-CTR | CTIS2023-506177-35-00 |
| EudraCT | EUCTR2020-005027-37-NL |
| CCMO | NL79015.028.21 |