Pembro/Carbo/Taxol in Endometrial Cancer

NCT02549209 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: BTCRC GYN15-013
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 6

Brief Summary

This is a single-arm, open-label, multi-center phase II study for subjects with measurable advanced or recurrent endometrial cancer using pembrolizumab in combination with carboplatin and paclitaxel chemotherapy. As this combination of agents has not been tested in this subject population, the first six subjects enrolled will constitute a safety run-in cohort.

Conditions

Endometrial Cancer; Endometrial Adenocarcinoma

Keywords

Pembrolizumab; Keytruda; Anti-Programmed [Cell] Death Protein 1 (PD-1) Antibody; Carboplatin; Paclitaxel

Outcome Measures

Primary Outcomes (1)

• Objective Response Rates (ORR)

  Objective response rate(ORR) is defined as the percentage of subjects with a partial response or complete response according to immune-related RECIST criteria. Immune-Related Response Criteria: Complete Response(irCR): Disappearance of all lesions in two consecutive observations not less than 4 wk apart. Partial Reponse (irPR): decrease in tumor burden ≥50 %relative to baseline confirmed by a consecutive assessment at least 4 wk after first documentation Stable Disease (irSD): not meeting criteria for irCR or irPR, in absence of irPD

  From start of treatment Day 1 (D1) and assessed for a maximum of 18 months

Secondary Outcomes (1)

• Proportion of Subjects Who Experience ≥ Grade 3 Toxicity According Per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 Criteria

  From time of consent to up to a maximum of 7 months(30 days following cessation of treatment )

Study Arms (1)

Investigational Treatment

EXPERIMENTAL

Subjects with no prior therapy: * Pembrolizumab administered at 200 mg * Paclitaxel administered at 175mg/m2 * Carboplatin administered at an AUC of 6 Subjects with prior external beam radiation therapy (XRT) and/or platinum-based chemotherapy must initiate paclitaxel and carboplatin at a reduced dose: * Pembrolizumab administered at 200 mg * Paclitaxel administered at 135mg/m2 * Carboplatin administered at an AUC of 5

Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg will be administered every 3 weeks for all subjects

Also known as: MK-3475, Keytruda®

Investigational Treatment

Paclitaxel DRUG

For subjects with no prior therapy, paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion. Subjects with prior XRT/platinum-based chemotherapy must initiate paclitaxel at 135mg/m2 and be administered as a 3-hour continuous IV infusion.

Also known as: Taxol®

Investigational Treatment

Carboplatin DRUG

For subjects with no prior therapy, carboplatin will be dosed at an AUC of 6 and given as an IV infusion in 250ml of D5W over 30 minutes. Subjects with prior XRT/platinum-based chemotherapy must initiate carboplatin at an AUC of 5 given as an IV infusion in 250ml of D5W over 30 minutes.

Also known as: Paraplatin®

Investigational Treatment

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration for protocol therapy.
• o NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0 or 1 within 28 days prior to registration for protocol therapy.
• Histological evidence of newly diagnosed Stage III or IV or recurrent endometrial carcinoma who have had definitive surgery for endometrial cancer (at least hysterectomy and bilateral salpingo-oophorectomy). Pathologic documentation of the recurrence (i.e., biopsy) will be performed per standard of care, at the treating physician's discretion. If a subject with recurrence is undergoing a biopsy for clinical indications and is willing and able, an optional collection of 3 frozen tissue cores of the recurrence site is requested for correlative analysis.
• Measurable disease according to RECIST v1.1 and obtained by imaging within 28 days prior to registration for protocol therapy. Disease in an irradiated field as the only site of measurable disease is acceptable only if there has been clear progression since completion of radiation treatment.
• The subject must have recovered (≤ grade 1) from the acute toxic effects of prior therapy.
• Prior treatment: Subjects may have received none or one platinum-based chemotherapy regimen and none or one non-platinum regimen. Subjects having received prior platinum-based chemotherapy must have a disease-free interval \> 6 months (be platinum sensitive).
• Prior therapy with hormones or biologic agents is allowed. These treatments must be discontinued at least 28 days prior to registration for protocol therapy.
• The subject must have completed radiation therapy at least 28 days prior to registration for protocol therapy, provided that toxicity has resolved to ≤ grade 1.
• NOTES: Subjects may have received prior radiation therapy for treatment of endometrial carcinoma. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy. Chemotherapy used for radiation sensitization is allowed. Chemotherapy used for radiation sensitization will not count as second chemotherapy regimen.
• Palliative radiation given primarily for symptom relief, without the intent to treat or cure the patient's endometrial cancer is excluded from the above criteria. Treatment-directed radiation will be defined as more than 30 Gy of radiation.
• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for at least 5 years.
• Female subjects must be of non-childbearing potential. Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for ≥1 year.
• Laboratory values must be obtained within 14 days prior to registration for protocol therapy. Note: Institutional/laboratory upper limit of normal (ULN)

You may not qualify if:

• Subjects with carcinosarcoma.
• Subjects who have a solitary central pelvic recurrence, which can be curatively resected.
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to registration for protocol therapy 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 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 registration for protocol therapy 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 registration for protocol therapy. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• NOTE: Subjects with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis.
• Treatment with any investigational agent within 28 days prior to registration for protocol therapy.
• Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Active autoimmune disease that has required systemic treatment in 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 received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registration for protocol therapy. (Prednisone (or equivalent) \< 10mg/ day is allowed).
• Has a known history of active TB (Bacillus Tuberculosis).
• Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Evidence of interstitial lung disease.
• Has an active infection requiring systemic therapy with the exception of an uncomplicated urinary tract infection.

Sponsors & Collaborators

• Daniela Matei, MD: lead
• Merck Sharp & Dohme LLC: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (6)

Ironwood Cancer and Research Centers

Mesa, Arizona, 85206, United States

Location

Northwestern University, Robert H. Lurie Cancer Center

Chicago, Illinois, 60611, United States

Location

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Links

• Big Ten Cancer Research Consortium Website

MeSH Terms

Conditions

Endometrial Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

(317) 634-5842

Study Officials

• Daniela Matei, M.D.

  Big Ten Cancer Research Consortium

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open-Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: September 11, 2015
• First Posted: September 15, 2015
• Study Start: August 22, 2017
• Primary Completion: December 12, 2019
• Study Completion: February 10, 2022
• Last Updated: March 2, 2022
• Results First Posted: November 30, 2021

Record last verified: 2022-02

Locations

US (6)