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.
OUTLINE: This is a multi-center study. INVESTIGATIONAL TREATMENT: To ensure the safety of this combination treatment, an initial safety run-in will be conducted for the first 6 subjects. This initial cohort of 6 subjects will be enrolled and treated with standard doses as described below. Based on toxicity analysis of the initial 6 subjects following completion of 18 weeks of treatment, it will be determined if an extended safety run-in period would be beneficial. In the absence of receiving any prior therapy, eligible subjects will be treated as follows on D1 of cycles lasting 21 days (3 weeks) for a maximum of 6 cycles: * Pembrolizumab 200mg will be administered as a 30-minute intravenous (IV) infusion every 3 weeks. * Paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion. * Carboplatin will be dosed at area under the curve (AUC) of 6 and given as an IV infusion in 250ml of D5W over 30 minutes. Subjects who have had prior radiotherapy/platinum-based chemotherapy must initiate paclitaxel and carboplatin at the following reduced dose levels if they have had prior external radiotherapy involving the whole pelvis or abdomen or over 50% of their spine, and/or prior platinum-based chemotherapy for this, or any other cancer. Eligible subjects will be treated as follows on Day 1 (D1) of cycles lasting 21 days (3 weeks) for a maximum of 6 cycles: * Pembrolizumab 200mg administered as a 30-minute intravenous (IV) infusion every 3 weeks. * Paclitaxel will be dosed at 135mg/m2 and be administered as a 3-hour continuous IV infusion. * Carboplatin will be dosed at an AUC of 5 and given as an IV infusion in 250ml of D5W over 30 minutes. Subsequent doses of paclitaxel and carboplatin may be escalated to the higher doses as indicated above, provided these subjects do not exhibit hematologic or nonhematologic toxicity \> Grade 1, except alopecia. The following laboratory values must be obtained within 14 days prior to registration for protocol therapy: Hematopoietic: * Hemoglobin (Hgb) \> 9 g/dL (without transfusion or erythropoietin (EPO) dependency within 7 days of assessment) * Platelets \> 100 K/mm3 * Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 Renal: * Creatinine or measured/calculated creatinine clearance (as calculated by institutional standard) ≤ 1.5 X institutional upper limits of normal (ULN) OR ≥60mL/min for subjects with creatinine levels \> 1.5 x institutional ULN Hepatic: * Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN * Aspartate aminotransferase (AST), alanine transaminase (ALT) or alkaline phosphatase (ALP) \< 2.5 x ULN OR ≤ 5 x ULN for subjects with liver metastases * Albumin ≥ 2.5 mg/dL Coagulation (Blood Clotting) Tests: * 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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Pembrolizumab 200 mg will be administered every 3 weeks for all subjects
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.
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.
Ironwood Cancer and Research Centers
Mesa, Arizona, United States
Northwestern University, Robert H. Lurie Cancer Center
Chicago, Illinois, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
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
Time frame: From start of treatment Day 1 (D1) and assessed for a maximum of 18 months
Proportion of Subjects Who Experience ≥ Grade 3 Toxicity According Per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 Criteria
Proportion of subjects who experience ≥ Grade 3 toxicity regardless of relation according per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 criteria while receiving pembrolizumab in combination with standard carboplatin/paclitaxel therapy
Time frame: From time of consent to up to a maximum of 7 months(30 days following cessation of treatment )
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University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
University of Minnesota
Minneapolis, Minnesota, United States