Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pembro/Carbo/Taxol in Endometrial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02549209
Recruitment Status : Recruiting
First Posted : September 15, 2015
Last Update Posted : March 11, 2019
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Hoosier Cancer Research Network
Information provided by (Responsible Party):
Daniela Matei, MD, Big Ten Cancer Research Consortium

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.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Endometrial Adenocarcinoma Drug: Pembrolizumab Drug: Paclitaxel Drug: Carboplatin Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open-Label
Primary Purpose: Treatment
Official Title: Phase II Study of Pembrolizumab in Combination With Carboplatin and Paclitaxel for Advanced or Recurrent Endometrial Adenocarcinoma
Actual Study Start Date : August 22, 2017
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Investigational Treatment

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
Pembrolizumab 200 mg will be administered every 3 weeks for all subjects
Other Names:
  • MK-3475
  • Keytruda®

Drug: Paclitaxel

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.

Other Name: Taxol®

Drug: Carboplatin

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.

Other Name: Paraplatin®




Primary Outcome Measures :
  1. Objective Response Rates (ORR) [ Time Frame: From start of treatment Day 1 (D1) and assessed for a maximum of 18 months ]
    Proportion of confirmed partial response (PR) and complete response (CR) rates per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria for evaluable subjects receiving pembrolizumab in combination with standard carboplatin/paclitaxel therapy.


Secondary Outcome Measures :
  1. Incidence of Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From start of treatment D1 and every treatment visit thereafter up to a maximum of 18 months ]
    Proportion of subjects who experience ≥ Grade 3 toxicity according per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 criteria while receiving pembrolizumab in combination with standard carboplatin/paclitaxel therapy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
  • Hemoglobin (Hgb) > 9 g/dL (without transfusion or EPO dependency within 7 days of assessment)
  • Platelets > 100 K/mm3
  • Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
  • Creatinine or measured/calculated creatinine clearance (as calculated by institutional standard) ≤ 1.5 X institutional ULN OR ≥60mL/min for subjects with creatinine levels > 1.5 x institutional ULN
  • Serum total bilirubin ≤ 1.5 ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
  • AST, ALT or alkaline phosphatase < 2.5 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 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 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.
  • Pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v4 criteria.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
  • Has received a live vaccine within 30 days prior to registration for protocol therapy.

    o 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02549209


Contacts
Layout table for location contacts
Contact: Dylan Cregar 317.634.5842 ext 38 dcregar@hoosiercancer.org
Contact: Daniela Matei, M.D. 312-695-6180 daniela.matei@northwestern.edu

Locations
Layout table for location information
United States, Arizona
Ironwood Cancer and Research Centers Recruiting
Mesa, Arizona, United States, 85206
Contact: Lisa Frick    480-398-7671    lfrick@ironwoodcrc.com   
Principal Investigator: Mario Pineda, MD         
United States, Illinois
Northwestern University, Robert H. Lurie Cancer Center Recruiting
Chicago, Illinois, United States, 60611
Contact: Daniela Matei, M.D.    312-695-6180    daniela.matei@northwestern.edu   
Northwestern Medicine Lake Forest Hospital Recruiting
Lake Forest, Illinois, United States, 60045
Contact: Valerie Nelson, MD    847-582-2134    cancertrials@northwestern.edu   
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Amber Bauchle    317-274-2869    adbauchl@iu.edu   
Principal Investigator: Jeanne Schilder, MD         
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Marian Anderson    319-353-4578    marian-andersen@uiowa.edu   
Principal Investigator: David Bender, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Erin Zielinski    612-624-0937    eezielin@umn.edu   
Principal Investigator: Deanna Teoh, MD         
Sponsors and Collaborators
Daniela Matei, MD
Merck Sharp & Dohme Corp.
Hoosier Cancer Research Network
Investigators
Layout table for investigator information
Study Chair: Daniela Matei, M.D. Big Ten Cancer Research Consortium

Additional Information:
Layout table for additonal information
Responsible Party: Daniela Matei, MD, Sponsor-Investigator, Big Ten Cancer Research Consortium
ClinicalTrials.gov Identifier: NCT02549209     History of Changes
Other Study ID Numbers: BTCRC GYN15-013
First Posted: September 15, 2015    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daniela Matei, MD, Big Ten Cancer Research Consortium:
Pembrolizumab
Keytruda
Anti-Programmed [Cell] Death Protein 1 (PD-1) Antibody
Carboplatin
Paclitaxel
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Endometrial Neoplasms
Uterine Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Pembrolizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological