- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02728830
A Study of Pembrolizumab on the Tumoral Immunoprofile of Gynecologic Cancers
A Pilot Study Investigating the Effect of Pembrolizumab on the Tumoral Immunoprofile of Gynecologic Cancers of Mullerian Origin
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Have histologically or cytologically confirmed gynecologic tumor of müllerian origin, specifically epithelial ovarian, fallopian tube, primary peritoneal, or uterine endometrial cancer.
- Have disease amenable to surgical resection.
- Be willing and able to provide written informed consent for the trial.
- Be at least 18 years of age on day of signing informed consent.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement of the investigator.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days of study drug administration:
7a. ANC ≥ 1,500/mcL
7b. Platelets ≥ 100,000/mcL
7c. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
7d. Serum creatinine ≤ 1.5 times the upper limit of normal or calculated creatinine clearance ≥ 60 mL/min for subject with creatinine levels > 1.5 times institutional upper limit of normal
7e. Serum total bilirubin ≤ 1.5 times the upper limit of normal or direct bilirubin ≤ the upper limit of normal with total bilirubin levels > 1.5 times upper limit of normal
7f. AST and ALT ≤ 2.5 times the upper limit of normal or ≤ 5 times the upper limit of normal for subjects with liver metastases
7g. Albumin > 2.5 mg/dL
7h. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
7i. Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
8. Female subjects 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.
9. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity until planned hysterectomy/oophorectomy. 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 a 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 study drug administration.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study drug administration.
- 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 received prior chemotherapy, targeted small molecule therapy, or radiation therapy for the current gynecologic malignancy.
NOTE: Subjects who have received treatment for a prior unrelated malignancy must have 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 known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, 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 study drug administration 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 study drug administration. 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious 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.
- 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).
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Pembrolizumab
Subjects will receive one dose of 200mg pembrolizumab by IV 14-21 days prior to surgery. Subjects will undergo standard surgical cytoreductive surgery as deemed appropriate by their gynecologic oncologist, followed by standard adjuvant chemotherapy for their cancer as deemed appropriate by their treating physician. If subject's disease does not get worse following standard of care chemotherapy, they will receive pembrolizumab in the maintenance setting every three weeks for up to a year. If subject's disease returns after completing a year of pembrolizumab and they have not had adverse reactions to pembrolizumab they may be eligible to continue receiving pembrolizumab for an additional year in the second course phase. |
Pembrolizumab 200mg IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Tumor Immune Infiltrates as Measured by PD-L1 Modified H-Score
Time Frame: Baseline and 14-21 Days
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This outcome measures the change in tumor immune infiltrates post-pembrolizumab versus pre-pembrolizumab as measured by the PD-L1 Modified H-score. Histological score (H-score) is a score that is comprised of intensity and percentage of staining and is used for assessing amount of protein (in this case PD-L1) present in a tissue sample. H-score is determined by adding of the percentages of cell staining at each intensity level multiplied by the membrane intensity of staining (0 (no staining), 1+ (weak staining), 2+ (medium staining), 3+(strong staining)). The H-score has a range of 0 to 300. Lower H-scores represent lower expression of PD-L1 in the tumor sample, while higher scores represent stronger expression of PD-L1 in the tumor samples. |
Baseline and 14-21 Days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity Profile: Frequency and Severity of Adverse Events as Assessed by CTCAE
Time Frame: 18 months
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Frequency and severity of adverse events associated with pembrolizumab when given to patients with newly diagnosed gynecologic cancers of müllerian origin prior to standard surgical therapy and as maintenance therapy after completion of chemotherapy.
All events experienced within the AE reporting time frame deemed probably, possibly, or definitely related to study drug above the reporting threshold of 4%.
Categorized by grade and frequency, defined using CTCAE 4.0 event name and grading.
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18 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory: Changes in Tumoral and Circulating Blood Immunoprofile
Time Frame: Baseline and 14-21 Days
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To characterize changes in the tumoral and circulating blood immunoprofile after administration of pembrolizumab.
Levels of immune and inflammatory mediators, profile of tumor immune infiltrates, and the expression of PD-L1 in pre-administration samples will be compared to post-administration surgical resection (including ascites) samples.
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Baseline and 14-21 Days
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Exploratory: Changes in Tumoral and Circulating Blood Immunoprofile for Those Who Enroll in Second Course Phase at Time of Recurrence
Time Frame: 18 months
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To evaluate changes in the tumoral and circulating blood immunoprofile at time of recurrence.
Levels of immune and inflammatory mediators, profile of tumor immune infiltrates, and the expression of PD-L1 in samples at time of recurrence will be compared to pre-administration and surgical samples.
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18 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Angeles A Secord, MD, Duke University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Uterine Neoplasms
- Uterine Diseases
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Fallopian Tube Diseases
- Ovarian Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Fallopian Tube Neoplasms
- Endometrial Neoplasms
- Carcinoma, Ovarian Epithelial
- Genital Neoplasms, Female
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- Pro00068544
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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