A Study of Pembrolizumab on the Tumoral Immunoprofile of Gynecologic Cancers

NCT02728830 | Completed Early Phase 1 Results

• 1 other identifier: Pro00068544
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The ultimate goal of the study is to identify potential biomarkers, immune gene expression signatures, and co-stimulatory pathways that may be used to understand the effect of immune checkpoint inhibitors on gynecologic cancers.

Conditions

Gynecologic Neoplasms; Epithelial Ovarian Cancer; Uterine Endometrial Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Keywords

gynecologic cancers; mullerian cancers; tumoral immunoprofile

Outcome Measures

Primary Outcomes (1)

• Change in Tumor Immune Infiltrates as Measured by PD-L1 Modified H-Score

  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

Secondary Outcomes (1)

• Toxicity Profile: Frequency and Severity of Adverse Events as Assessed by CTCAE

  18 months

Other Outcomes (2)

• Exploratory: Changes in Tumoral and Circulating Blood Immunoprofile

  Baseline and 14-21 Days

• Exploratory: Changes in Tumoral and Circulating Blood Immunoprofile for Those Who Enroll in Second Course Phase at Time of Recurrence

  18 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

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.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab 200mg IV

Also known as: Keytruda

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. ANC ≥ 1,500/mcL
• b. Platelets ≥ 100,000/mcL
• c. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• d. 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
• e. 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
• f. AST and ALT ≤ 2.5 times the upper limit of normal or ≤ 5 times the upper limit of normal for subjects with liver metastases
• g. Albumin \> 2.5 mg/dL
• h. 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AA Secord: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Genital Neoplasms, Female; Carcinoma, Ovarian Epithelial; Endometrial Neoplasms; Fallopian Tube Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Fallopian Tube Diseases

Results Point of Contact

• Title: Dr. Angeles Alvarez Secord
• Organization: Duke Cancer Center

secor002@mc.duke.edu

919-684-3765

Study Officials

• Angeles A Secord, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Obstetrics & Gynecology

Study Record Dates

• First Submitted: March 31, 2016
• First Posted: April 5, 2016
• Study Start: June 1, 2016
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2022
• Last Updated: February 21, 2024
• Results First Posted: July 9, 2020

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)