Ignite Creation Date:
2025-12-24 @ 4:26 PM
Ignite Modification Date:
2025-12-27 @ 6:16 PM
Study NCT ID:
NCT02365766
Status:
COMPLETED
Last Update Posted:
2025-03-18
First Post:
2015-02-11
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Neoadjuvant Pembrolizumab in Combination With Gemcitabine Therapy in Cis-eligible/Ineligible UC Subjects
Sponsor:
Jason R. Brown
Organization:
Study Overview
Official Title:
Phase Ib/II Study of Neoadjuvant Pembrolizumab With Gemcitabine-Cisplatin (Cisplatin-Eligible) or Gemcitabine (Cisplatin-Ineligible) in Subjects With T2-4aN0M0 Urothelial Cancer: HCRN GU14-188
Status:
COMPLETED
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a pre-surgical study involving subjects with muscle invasive bladder cancer, or urothelial cancer, who are candidates for neoadjuvant therapy. It is is a two-part trial with a one-arm phase Ib portion followed by a two-arm phase II portion. The study treatment is stratified into two cohorts based on cisplatin eligibility.
Detailed Description:
OUTLINE: This is a multi-center study.
INVESTIGATIONAL TREATMENT:
Phase Ib Dose-Finding Cohort I Cisplatin-Eligible:
Phase Ib is a 3+3 design for the cisplatin-eligible group only. Cisplatin-eligible subjects receive: gemcitabine 1000mg/m2 IV D1 and D8 every 21 days repeated for 4 cycles; cisplatin 70mg/m2 IV D1 and D8 every 21 days, repeated for 4 cycles. (Subjects with Ccr of 50-59 mL/min must follow split dosing of cisplatin over two days). Pembrolizumab will be given every 3 weeks for 5 doses, with a starting dose of 200 mg. NOTE: the last dose of pembrolizumab falls on what would be D8 of a 5th 'chemo' cycle, however gemcitabine/cisplatin is NOT GIVEN.
Phase II Arm A: Cohort I Cisplatin-Eligible:
Cisplatin-eligible subjects receive: gemcitabine 1000mg/m2 IV D1 and D8 every 21 days repeated for 4 cycles; cisplatin 70mg/m2 IV D1 and D8 every 21 days, repeated for 4 cycles. (Subjects with Ccr of 50-59 mL/min must follow split dosing of cisplatin over two days). Pembrolizumab at recommended phase II dose (RP2D) is given every 3 weeks for 5 doses starting with C1D8. NOTE: the last dose of pembrolizumab falls on what would be day 8 of a 5th 'chemo' cycle, however gemcitabine/cisplatin is NOT GIVEN. Cohort I treatment with gemcitabine and cisplatin will continue for a maximum of 4 cycles (cycle = 21days).
Phase II Arm B: Cohort II:
Cisplatin-ineligible subjects receive gemcitabine 1000mg/m2 IV D1, D8 and D15 every 28 days, repeated for 3 cycles. Pembrolizumab at RP2D is given every 3 weeks for 5 doses starting with C1D8. NOTE: due to the timing of gemcitabine cycles every 4 weeks, and every three week dosing of pembrolizumab, there are two doses of pembrolizumab given during cycle 2: D1 and D22. Additionally, the last dose of pembrolizumab falls on what would be D8 of a 4th 'chemo' cycle; however gemcitabine is NOT GIVEN. Cohort II treatment with gemcitabine will continue for a maximum of 3 cycles (cycle = 28 days)
Subjects will then have surgery to remove their primary tumor within 2-7 weeks after their last dose of neoadjuvant therapy.
Eastern Cooperative Oncology Group (ECOC) performance status: 0-1 for cisplatin-eligible subjects; 0-2 for cisplatin-ineligible subjects.
Demonstrate adequate organ function as defined by the following laboratory values at study entry. All screening labs should be performed within 28 days of C1D1.
Hematopoetic:
* Absolute neutrophil count (ANC) ≥1,500 /mcL
* Absolute lymphocyte count ≥350 mcL
* Platelets ≥100,000 / mcL
* Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
Renal:
* Measured or calculated creatinine clearance ≥30 mL/min
Hepatic:
* Serum total bilirubin ≤ 1.25 X ULN OR ≤ 2.5 x ULN for subjects with Gilbert's disease
* Aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT) ≤ 2 X ULN
Coagulation:
* International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
* Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy and as long as PT or PTT is within therapeutic range of intended use of anticoagulants
INVESTIGATIONAL TREATMENT:
Phase Ib Dose-Finding Cohort I Cisplatin-Eligible:
Phase Ib is a 3+3 design for the cisplatin-eligible group only. Cisplatin-eligible subjects receive: gemcitabine 1000mg/m2 IV D1 and D8 every 21 days repeated for 4 cycles; cisplatin 70mg/m2 IV D1 and D8 every 21 days, repeated for 4 cycles. (Subjects with Ccr of 50-59 mL/min must follow split dosing of cisplatin over two days). Pembrolizumab will be given every 3 weeks for 5 doses, with a starting dose of 200 mg. NOTE: the last dose of pembrolizumab falls on what would be D8 of a 5th 'chemo' cycle, however gemcitabine/cisplatin is NOT GIVEN.
Phase II Arm A: Cohort I Cisplatin-Eligible:
Cisplatin-eligible subjects receive: gemcitabine 1000mg/m2 IV D1 and D8 every 21 days repeated for 4 cycles; cisplatin 70mg/m2 IV D1 and D8 every 21 days, repeated for 4 cycles. (Subjects with Ccr of 50-59 mL/min must follow split dosing of cisplatin over two days). Pembrolizumab at recommended phase II dose (RP2D) is given every 3 weeks for 5 doses starting with C1D8. NOTE: the last dose of pembrolizumab falls on what would be day 8 of a 5th 'chemo' cycle, however gemcitabine/cisplatin is NOT GIVEN. Cohort I treatment with gemcitabine and cisplatin will continue for a maximum of 4 cycles (cycle = 21days).
Phase II Arm B: Cohort II:
Cisplatin-ineligible subjects receive gemcitabine 1000mg/m2 IV D1, D8 and D15 every 28 days, repeated for 3 cycles. Pembrolizumab at RP2D is given every 3 weeks for 5 doses starting with C1D8. NOTE: due to the timing of gemcitabine cycles every 4 weeks, and every three week dosing of pembrolizumab, there are two doses of pembrolizumab given during cycle 2: D1 and D22. Additionally, the last dose of pembrolizumab falls on what would be D8 of a 4th 'chemo' cycle; however gemcitabine is NOT GIVEN. Cohort II treatment with gemcitabine will continue for a maximum of 3 cycles (cycle = 28 days)
Subjects will then have surgery to remove their primary tumor within 2-7 weeks after their last dose of neoadjuvant therapy.
Eastern Cooperative Oncology Group (ECOC) performance status: 0-1 for cisplatin-eligible subjects; 0-2 for cisplatin-ineligible subjects.
Demonstrate adequate organ function as defined by the following laboratory values at study entry. All screening labs should be performed within 28 days of C1D1.
Hematopoetic:
* Absolute neutrophil count (ANC) ≥1,500 /mcL
* Absolute lymphocyte count ≥350 mcL
* Platelets ≥100,000 / mcL
* Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
Renal:
* Measured or calculated creatinine clearance ≥30 mL/min
Hepatic:
* Serum total bilirubin ≤ 1.25 X ULN OR ≤ 2.5 x ULN for subjects with Gilbert's disease
* Aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT) ≤ 2 X ULN
Coagulation:
* International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
* Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy and as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: