Pembrolizumab, Carboplatin, and Paclitaxel in Treating Patients with Stage III-IV or Recurrent Endometrial Cancer

Status: Active

Description

This phase II trial studies how well pembrolizumab, carboplatin, and paclitaxel work in treating patients with endometrial cancer that is stage III-IV or has come back. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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, carboplatin, and paclitaxel may work better in treating patients with endometrial cancer.

Eligibility Criteria

Inclusion Criteria

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration for protocol therapy * NOTE: HIPAA authorization may be included in the informed consent or obtained separately
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days prior to registration for protocol therapy
  • Histological evidence of primary 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) is required if there is only a single site of disease on imaging and that site is less than 2 cm; 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 Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 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 * NOTES: Subjects may have received a single platinum-based cytotoxic chemotherapy regimen; subjects having received prior cytotoxic chemotherapy must have completed their treatment more than 6 months prior to registration; subjects may have received prior therapy with hormones or biologic agents, but such therapies must be discontinued at least 28 days prior to registration for protocol therapy
  • The subject must have completed prior radiation therapy at least 28 days prior to registration for protocol therapy * 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
  • Subjects with recurrence must have a documented complete response upon completion of initial definitive therapy
  • 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
  • Hemoglobin (Hgb) > 9 g/dL (without transfusion or erythropoietin [EPO] dependency within 7 days of assessment)
  • Platelets > 100 K/mm^3
  • Absolute neutrophil count (ANC) >= 1.5 K/mm^3
  • Creatinine or measured/calculated creatinine clearance (as calculated by institutional standard) =< 1.5 X institutional upper limit of normal (ULN) OR >= 60 mL/min for subjects with creatinine levels > 1.5 x institutional ULN
  • Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase < 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases
  • Albumin >= 2.5 mg/dL
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anti-coagulant therapy as long as partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anti-coagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria

  • 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 computed tomography (CT) scan or brain magnetic resonance imaging (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
  • 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 active, non-infectious pneumonitis
  • Evidence of interstitial lung disease
  • Has an active infection requiring systemic therapy with the exception of an uncomplicated urinary tract infection
  • Pre-existing peripheral neuropathy that is >= grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) v4 criteria
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has a known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [quantitative] is detected)
  • Has received a live vaccine within 30 days prior to registration for protocol 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
  • History of solid organ or stem cell transplant requiring immunosuppressive medications

Locations & Contacts

Illinois

Chicago
Northwestern University
Status: Approved
Contact: Daniela Elena Matei
Email: daniela.matei@northwestern.edu
Lake Forest
Northwestern Medicine Lake Forest Hospital
Status: Active
Contact: Valerie Marie Nelson
Phone: 847-535-7285

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: Active
Contact: Christina Frances Cooper
Phone: 317-274-0220
Email: cfcooper@iu.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To estimate the objective response rate of pembrolizumab in combination with standard carboplatin/paclitaxel in subjects with measurable advanced or recurrent endometrial cancer.

SECONDARY OBJECTIVES:

I. To determine the toxicities of pembrolizumab in combination with standard carboplatin/paclitaxel in subjects with advanced or recurrent endometrial cancer.

TERTIARY OBJECTIVES:

I. To evaluate potential biomarkers or prognostic factors for those who may respond to pembrolizumab.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes, paclitaxel IV over 3 hours, and carboplatin IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 18 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Northwestern University

Principal Investigator
Daniela Elena Matei

Trial IDs

Primary ID BTCRC GYN15-013
Secondary IDs NCI-2017-01660, STU00204968
Clinicaltrials.gov ID NCT02549209