Brief Title
Trial of Pembrolizumab Following Weekly Paclitaxel for Platinum-resistant Ovarian, Fallopian Tube or Peritoneal Cancer
Official Title
Phase II Trial of Maintenance Pembrolizumab Following Weekly Paclitaxel for Platinum-resistant Ovarian, Fallopian Tube or Peritoneal Cancer
Brief Summary
The overall aim of the study is to demonstrate a clinically meaningful extension of
progression free survival using maintenance pembrolizumab. The aim of the translational
research is to study the immune microenvironment before and during pembrolizumab therapy.
Detailed Description
This study aims to investigate the effect of maintenance pembrolizumab in patients who have
undergone treatment with weekly paclitaxel for platinum-resistant recurrent ovarian cancer
and have either responded or have not progressed after a minimum of 4 cycles of treatment.
In this study patients will receive 3 weekly pembrolizumab until progression and the
investigators will monitor the immune microenvironment by tumour biopsy and blood sampling
before starting pembrolizumab and again before cycle 4 of treatment. The clinical endpoint
will be to demonstrate a worthwhile improvement in the 6 month median PFS and to study
possible predictive markers or response to pembrolizumab. This is a non-randomised phase II
study, and the population may be different from those who received paclitaxel and
bevacizumab.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression-Free Survival (PFS) measured from start of study treatment to the date of objective progression (investigator assessed using RECIST 1.1) or date of death from any cause (in the absence of progression).
Secondary Outcome
Overall survival measured from start of study treatment to the date of death from any cause
Condition
Ovarian Cancer
Intervention
Pembrolizumab
Study Arms / Comparison Groups
Treatment
Description: All patient will receive Pembrolizumab (100 mg/ 4mL) every 3 weeks for a maximum of 2 years. Pembrolizumab 200mg will be administered as a 30 minute IV infusion every 3 weeks.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
28
Start Date
May 16, 2019
Completion Date
November 16, 2022
Primary Completion Date
November 16, 2020
Eligibility Criteria
Inclusion Criteria:
1. Patients must have a diagnosis of high grade recurrent ovarian/fallopian tube or
primary non-mucinous peritoneal cancer
2. Be willing and able to provide written informed consent for the trial, indicating that
the patient has been informed of and understands the experimental nature of the study,
possible risks and benefits, trial procedures, and alternative options
3. Be >=18 years of age on day of signing informed consent
4. Patients should be treated with a minimum of 4 cycles of weekly paclitaxel for
recurrent disease. [Non-platinum-based therapy given for CT/MR documented recurrence
where further platinum therapy considered unsuitable]
5. Patients can have had up to 3 prior lines of platinum-based chemotherapy for ovarian
cancer before starting weekly paclitaxel
6. Patients must have achieved at least stable disease or response following a minimum of
four cycles of weekly paclitaxel (measured by CT/MR)
7. Trial treatment with pembrolizumab must start within 8 weeks after last paclitaxel
dose
8. Availability of archival tissue
9. Patient has disease amenable to biopsy after paclitaxel (baseline biopsy)
10. Patient is willing to have a biopsy at baseline and before start of the 4th cycle of
pembrolizumab
11. Patient has measurable disease based on RECIST v1.1
12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
13. Willing and able to comply with the protocol for the duration of the study, including
the treatment plan, investigations required and follow up visits
14. Demonstrate adequate organ function as defined in the protocol, all screening labs
should be performed within 10 days of treatment initiation.
15. Patients of childbearing potential should have a negative urine or serum pregnancy
test. If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required
16. Patients of childbearing potential must be willing to use an adequate method of
contraception as outlined in protocol from the start of treatment through to 4 months
after the last dose of study medication
Exclusion criteria:
1. Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40,
CD137)
2. Has a diagnosis of low grade or mucinous ovarian cancer
3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (dose
exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive
therapy within 7 days prior to the first dose of trial treatment (n.b. the use of
physiologic doses of corticosteroids may be approved after consultation with UCL CTC).
Use of inhaled steroids is permitted.
4. Has a known history of active TB (Bacillus Tuberculosis)
5. Has known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known Hepatitis C virus (defined as HCV RNA [qualitative] is detected)*
6. Has a known history of Human Immunodeficiency Virus (HIV)
7. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks (could consider shorter interval for kinase inhibitors or other short
half-life drugs) prior to registration.
Note: Participants must have recovered from all AEs due to previous therapies to
≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible
8. Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (a maximum of 2 weeks radiotherapy is allowed) to non-CNS
disease
9. Patients with concurrent or previous malignancy within the last 5 years (except Stage
I grade 1 endometrial cancer; in situ cervical cancer; DCIS of the breast) that could
compromise assessment of the primary or secondary endpoints of the trial
10. Active central nervous system (CNS) metastases and/or carcinomatous meningitis;
patients with previously treated brain metastases may participate
11. Has active autoimmune disease that required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, corticosteroids (at doses >10mg prednisolone
daily or equivalent) or immunosuppressive drugs) except vitiligo or resolved childhood
asthma/atopy. Replacement hormone therapy (e.g. levothyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
permitted
12. Has a corrected serum calcium of >1.5 x ULN despite maximal antihypercalcaemic therapy
13. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis or has a history of interstitial lung disease
14. Has a newly diagnosed venous thrombotic event (e.g. PE, DVT) untreated with
anticoagulation. Patients must have received at least 14 days of anticoagulation for a
new thrombotic event and be suitable for continued therapeutic anticoagulation during
trial participation. Patients are excluded if they have a history of arterial
thrombosis
15. Has an active infection requiring systemic therapy
16. Has symptoms of bowel obstruction in the past three months
17. Any serious and/or unstable pre-existing medical, psychiatric or other condition that,
in the treating clinician's judgement could interfere with patient safety or obtaining
informed consent
18. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
19. Is pregnant or breastfeeding, or expecting to conceive children within the projected
duration of the trial, starting with the screening visit through to 4 months after the
last dose of trial treatment
20. Has received a live vaccine within 30 days of planned start of study treatment.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
UCL Cancer Trials Centre, +44 (0)2076799016, [email protected]
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT03430700
Organization ID
UCL/17/0629
Responsible Party
Sponsor
Study Sponsor
University College, London
Collaborators
Merck Sharp & Dohme Corp.
Study Sponsor
UCL Cancer Trials Centre, Study Chair, UCL
Verification Date
September 2019