Brief Title
Pembrolizumab and Carboplatin in Treating Patients With Relapsed or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Official Title
Anti-PD-1 Therapy in Combination With Platinum Chemotherapy for Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Brief Summary
This phase I/II trial studies how well pembrolizumab and carboplatin work in treating
patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back
(relapsed) or has not responded to previous treatment (refractory). Immunotherapy with
monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the
cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in
chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving pembrolizumab and carboplatin with platinum resistant chemotherapy may work
better than platinum chemotherapy alone in treating patients with ovarian, fallopian tube, or
primary peritoneal cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the clinical response rate of platinum chemotherapy and pembrolizumab
(MK-3475) in platinum chemotherapy pretreated ovarian, fallopian tube, and primary
peritoneal.
II. To examine whether retreatment with platinum chemotherapy in platinum resistant ovarian,
fallopian tube, and primary peritoneal cancers improves progression free survival by
concurrent administration of MK-3475.
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of concurrent administration of MK-3475 with
platinum chemotherapy in patients with platinum resistant recurrent ovarian, fallopian tube,
and primary peritoneal cancers.
II. To determine the relationship between PD-L1 expression and response to the combination of
MK-3475 and platinum.
III. To assess the overall survival of patients treated with the combination of MK-3475 and
platinum.
EXPLORATORY OBJECTIVE:
I. To explore whether treatment with MK-3475 and platinum alters soluble factors in sera,
peripheral immune responses and immune cell profile.
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and carboplatin IV
over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for
1 year, every 6 months for 1 year, and then every 12 weeks thereafter.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Response rate (RR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Secondary Outcome
Incidence of adverse events evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Condition
Recurrent Fallopian Tube Carcinoma
Intervention
Carboplatin
Study Arms / Comparison Groups
Treatment (pembrolizumab, carboplatin)
Description: Patients receive pembrolizumab IV over 30 minutes on day 1 and carboplatin IV over 30 minutes on days 8 and 15. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
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
29
Start Date
March 14, 2017
Completion Date
December 31, 2023
Primary Completion Date
March 31, 2021
Eligibility Criteria
Inclusion Criteria:
- Have a diagnosis of ovarian, fallopian tube, or primary peritoneal cancer patients who
had a complete response to primary treatment with platinum based chemotherapy, have
progressed within 6 months of completing platinum based chemotherapy and have
subsequently received at least one, non-platinum-based, therapy
- Have relapsed, refractory, or progressive disease following last line of treatment
- Have estimated life expectancy of at least 3 months
- Be willing and able to provide written informed consent/assent for the trial
- Have measurable disease with at least 1 unidimensional lesion based on Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
performance scale
- Absolute neutrophil count (ANC) >= 1,500/mcL (within 10 days of treatment initiation)
- Platelets >= 100,000/mcL (within 10 days of treatment initiation)
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)
dependency (within 7 days of assessment) (within 10 days of treatment initiation)
- Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated
creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine
levels > 1.5 X institutional ULN (within 10 days of treatment initiation)
*Creatinine clearance should be calculated per institutional standard
- Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total
bilirubin levels > 1.5 ULN (within 10 days of treatment initiation)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
ULN OR =< 5 X ULN for subjects with liver metastases (within 10 days of treatment
initiation)
- Albumin >= 2.5 mg/dL (within 10 days of treatment initiation)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless
subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
time (PTT) is within therapeutic range of intended use of anticoagulants (within 10
days of treatment initiation)
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulants (within 10 days of treatment initiation)
- 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
- Female subjects of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 120 days after the last dose of study medication; subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year
Exclusion Criteria:
- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy within 4 weeks of the first
dose of treatment
- 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
* Short-term administration of systemic steroids (i.e., for allergic reactions or the
management of immune related adverse events [irAEs]) is allowed
- Has 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
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
- Note: subjects with =< grade 2 neuropathy are an exception to this criterion and
may qualify for the study
- Note: if subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting therapy
- Has a known additional malignancy that is progressing or requires active treatment;
exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer
- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis; subjects with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment; this exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability
- 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
- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive children within the projected
duration of the trial, starting with the pre-screening or screening visit through 120
days after the last dose of trial treatment
- Clinically significant cardiovascular disease
- Known severe hypersensitivity reactions to monoclonal antibodies or carboplatin >=
grade 3, any history of anaphylaxis, or uncontrolled asthma
- Has received prior therapy with pembrolizumab
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
detected)
- Has received a live vaccine within 30 days of planned start of study therapy
- Note: seasonal influenza vaccines for injection are generally inactivated flu
vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)
are live attenuated vaccines, and are not allowed
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
John Liao, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03029598
Organization ID
9740
Secondary IDs
NCI-2016-01962
Responsible Party
Sponsor
Study Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
Study Sponsor
John Liao, Principal Investigator, Fred Hutch/University of Washington Cancer Consortium
Verification Date
October 2020