Ovarian Cancer
Conditions
Keywords
Ovarian, platinum, pembrolizumab, taxane
Brief summary
Phase II single arm, open label, nonrandomized study. The aim of our study is to assess the Progression Free Survival (PFS) in suboptimally cytoreduced epithelial ovarian/ primary peritoneal/ fallopian tube cancer patients treated with the novel combination of carboplatin every 21 days (triweekly) /weekly paclitaxel IV with pembrolizumab IV followed by maintenance pembrolizumab IV.
Detailed description
Utilization of combination standard intravenous chemotherapy with intravenous pembrolizumab (for 6 cycles) in first line treatment of patients with advanced ovarian cancer post surgery with any residual disease. This will be followed by single agent intravenous pembrolizumab (every 3 weeks) for 12 additional cycles.
Interventions
DRUGPembrolizumab
IV every 21 days at 200 mg
DRUGCarboplatin
IV every 21 days
DRUGPaclitaxel
IV infusion (80mg/m2) every 7 days for 6 cycles
Sponsors
The Cleveland Clinic
Merck Sharp & Dohme LLC
Medical College of Wisconsin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have advance stage III/IV epithelial ovarian, fallopian tube or primary peritoneal cancer * Be willing and able to provide written informed consent/assent for the trial. * Be 18 years of age or older on day of signing informed consent. * Suboptimal cytoreductive surgery defined as any residual disease noted per operative report and/or have measurable/macroscopic disease (defined as target and/or non-target lesions) based on RECIST 1.1. * Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor. * Have a performance status of 0, 1 or 2 on the ECOG Performance Scale. * Demonstrate adequate organ function * All screening labs should be performed within 28 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. * 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.
Exclusion criteria
* Is 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. * 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. * 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: 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 history of (non-infectious) pneumonitis that required steroids or current pneumonitis. * Has a known additional malignancy within the last 3 years, or 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. * 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * 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. * Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study. The investigator should consult the Study Chair. * 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. * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. * Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Patients with borderline ovarian tumors, recurrent epithelial ovarian/ primary peritoneal cancer/fallopian tube cancer or non-epithelial ovarian cancer are not eligible. * Has received a live vaccine within 30 days of planned start of study therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) of Combination Platinum Based Therapy With Anti-Programmed Death (PD)-1 Therapy Followed by Maintenance Anti-PD-1 Therapy in Patients With Epithelial Ovarian Cancer (EOC). | measured from date of completion of primary therapy to the date of the first clinical, biochemical or radiologic evidence of disease progression or death due to any cause | Time to progression free survival (PFS) is the period from study entry (first dose of therapy) until disease progression, death or date of last contact. All patients underwent baseline computed tomographic scans prior to initiation of therapy. The residual disease information was collected from surgical operative reports as well as post operative CT scans. Treatment responses were assessed with CA 125 at each cycle of therapy. CT scans were performed post-operatively prior to initiation of systemic therapy, at the completion of combination platinum, taxane, and pembrolizumab therapy, and at the completion of maintenance pembrolizumab therapy. CT scans were also performed with increasing CA 125 or if clinically indicated per treating physician and assessments were made using response evaluation criteria in solid tumor (RECIST) criteria defined as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in non-target l |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monitor Quality of Life During Combination Therapy and Single Agent Maintenance Therapy With Anti-PD-1 Therapy With the Functional Assessment of Cancer Therapy- Ovarian (FACT- O) Surveys at Intervals During Therapy. | Time of enrollment until 18 months from initiation of therapy | Each cycle is 21 days. All participants were asked to complete FACT-O surveys at baseline/ time of enrollment, at 3 months, 6 months and 18 months from initiation of therapy. FACT-O is a validated 26-item summary score 112 points that captures the FACT-General (FACT-G) QOL dimensions of Physical Well-Being (7 items), Functional Well-Being (7 items), and an Ovarian Cancer Subscale (12 items). FACT-0 is a survey with 39 items self administered survey. Each item is scored on 5 point Likert-type scale. The FACT-0 scoring range is from 0-44. The subscale scoring ranges for FACT-G is 0-108. The higher the total score the better the patient well-being. the outcome measure data represent FACT-G scoring as it is the section that pertains to QOL. https://www.facit.org/measures/FACT-O |
Other
| Measure | Time frame | Description |
|---|---|---|
| PD-L1 Expression in Preserved Tissue Obtained at the Time of Initial Diagnosis for Patients | At enrollment tissue from cytoreductive surgery will be obtained from pathology blocks. | PD-L1 expression in preserved tissue obtained at the time of initial diagnosis for patients with suboptimally cytoreduced ovarian cancer using immunohistochemistry (IHC) of initial tumor samples and correlate with clinical outcomes of response and survival. |
Countries
United States
Participant flow
Recruitment details
Patients enrolled from academic gyn oncology practice between 2016 and 2020
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy Combined With Pembrolizumab Single arm study:
Pembrolizumab IV every 21 days (200 mg) Carboplatin IV every 21 days Paclitaxel IV infusion (80 mg/m2) every 7 days for 6 cycles Followed by 12 months pembrolizumab IV every 21 days
Pembrolizumab: IV every 21 days at 200 mg
Carboplatin: IV every 21 days
Paclitaxel: IV infusion (80mg/m2) every 7 days for 6 cycles | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Chemotherapy Combined With Pembrolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 64 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 29 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 0 Participants |
| Stage III and IV | 29 units on a scale |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 29 |
| other Total, other adverse events | 0 / 29 |
| serious Total, serious adverse events | 7 / 29 |
Outcome results
Primary
Progression Free Survival (PFS) of Combination Platinum Based Therapy With Anti-Programmed Death (PD)-1 Therapy Followed by Maintenance Anti-PD-1 Therapy in Patients With Epithelial Ovarian Cancer (EOC).
Time to progression free survival (PFS) is the period from study entry (first dose of therapy) until disease progression, death or date of last contact. All patients underwent baseline computed tomographic scans prior to initiation of therapy. The residual disease information was collected from surgical operative reports as well as post operative CT scans. Treatment responses were assessed with CA 125 at each cycle of therapy. CT scans were performed post-operatively prior to initiation of systemic therapy, at the completion of combination platinum, taxane, and pembrolizumab therapy, and at the completion of maintenance pembrolizumab therapy. CT scans were also performed with increasing CA 125 or if clinically indicated per treating physician and assessments were made using response evaluation criteria in solid tumor (RECIST) criteria defined as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in non-target l
Time frame: measured from date of completion of primary therapy to the date of the first clinical, biochemical or radiologic evidence of disease progression or death due to any cause
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy Combined With Pembrolizumab | Progression Free Survival (PFS) of Combination Platinum Based Therapy With Anti-Programmed Death (PD)-1 Therapy Followed by Maintenance Anti-PD-1 Therapy in Patients With Epithelial Ovarian Cancer (EOC). | 13.2 months |
Secondary
Monitor Quality of Life During Combination Therapy and Single Agent Maintenance Therapy With Anti-PD-1 Therapy With the Functional Assessment of Cancer Therapy- Ovarian (FACT- O) Surveys at Intervals During Therapy.
Each cycle is 21 days. All participants were asked to complete FACT-O surveys at baseline/ time of enrollment, at 3 months, 6 months and 18 months from initiation of therapy. FACT-O is a validated 26-item summary score 112 points that captures the FACT-General (FACT-G) QOL dimensions of Physical Well-Being (7 items), Functional Well-Being (7 items), and an Ovarian Cancer Subscale (12 items). FACT-0 is a survey with 39 items self administered survey. Each item is scored on 5 point Likert-type scale. The FACT-0 scoring range is from 0-44. The subscale scoring ranges for FACT-G is 0-108. The higher the total score the better the patient well-being. the outcome measure data represent FACT-G scoring as it is the section that pertains to QOL. https://www.facit.org/measures/FACT-O
Time frame: Time of enrollment until 18 months from initiation of therapy
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Chemotherapy Combined With Pembrolizumab | Monitor Quality of Life During Combination Therapy and Single Agent Maintenance Therapy With Anti-PD-1 Therapy With the Functional Assessment of Cancer Therapy- Ovarian (FACT- O) Surveys at Intervals During Therapy. | screening | 85 score on a scale |
| Chemotherapy Combined With Pembrolizumab | Monitor Quality of Life During Combination Therapy and Single Agent Maintenance Therapy With Anti-PD-1 Therapy With the Functional Assessment of Cancer Therapy- Ovarian (FACT- O) Surveys at Intervals During Therapy. | 3 months | 88 score on a scale |
| Chemotherapy Combined With Pembrolizumab | Monitor Quality of Life During Combination Therapy and Single Agent Maintenance Therapy With Anti-PD-1 Therapy With the Functional Assessment of Cancer Therapy- Ovarian (FACT- O) Surveys at Intervals During Therapy. | 6 months | 83.9 score on a scale |
| Chemotherapy Combined With Pembrolizumab | Monitor Quality of Life During Combination Therapy and Single Agent Maintenance Therapy With Anti-PD-1 Therapy With the Functional Assessment of Cancer Therapy- Ovarian (FACT- O) Surveys at Intervals During Therapy. | 18 months | 86 score on a scale |
Other Pre-specified
PD-L1 Expression in Preserved Tissue Obtained at the Time of Initial Diagnosis for Patients
PD-L1 expression in preserved tissue obtained at the time of initial diagnosis for patients with suboptimally cytoreduced ovarian cancer using immunohistochemistry (IHC) of initial tumor samples and correlate with clinical outcomes of response and survival.
Time frame: At enrollment tissue from cytoreductive surgery will be obtained from pathology blocks.