Phase 2 Study of Pembrolizumab in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy

NCT02690558 | Completed Phase 2 Results DMC

• 1 other identifier: LCCC1520
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate whether adding pembrolizumab (Keytruda) to the combination of gemcitabine and cisplatin will improve shrinkage of the tumor before having a cystectomy, for people with muscle-invasive bladder cancer (MIBC).

Conditions

Bladder Cancer

Keywords

muscle-invasive

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects That Reach Pathological Downstaging (Response) at the Time of Cystectomy

  Pathologic (p) anatomic stage for bladder cancer uses the American Joint Committee on Cancer (AJCC) Tumor/Nodes/Metastasis (TNM) system, which is based on: Size of primary tumor (T) and whether it has grown into nearby areas. Spread to regional lymph nodes (N). Spread (metastasis; M) to other organs of the body. Once the T, N, and M categories have been determined, this information is combined into a prognostic group. Higher numbers mean the cancer is more advanced. Pathologic staging is based on the operative and pathology report from cystectomy at the local site. A pathologic response or downstaging is defined as a reduction in stage to below pathological tumor stage 2 (\<pT2) (pT0-T1N0M0)

  14 weeks of treatment plus cystectomy within 70 days after treatment

Secondary Outcomes (4)

• Percentage of Subjects That Reach Complete Pathologic Response (pT0) at the Time of Cystectomy

  14 weeks of treatment plus cystectomy within 70 days of treatment

• Event Free Survival

  14 weeks of treatment plus 5 years of followup

• Overall Survival (OS)

  14 weeks of treatment plus 3 years or until death

• Number of Participants With Treatment Related Adverse Events.

  14 weeks of treatment plus 30 days for toxicity followup

Study Arms (1)

pembrolizumab, gemcitabine and cisplatin

EXPERIMENTAL

There is one arm in this study. Subjects will receive Pembrolizumab 200mg IV on day 1 in combination with cisplatin 35mg/m2 and gemcitabine 1000mg/m2 on day 1 and day 8 every 3 weeks for 4 cycles over 12 weeks.

Drug: pembrolizumab, gemcitabine and cisplatin

Interventions

pembrolizumab, gemcitabine and cisplatin DRUG

neoadjuvant administration of pembrolizumab with gemcitabine and cisplatin prior to cystectomy

Also known as: Keytruda, MK-3475

pembrolizumab, gemcitabine and cisplatin

Eligibility Criteria

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

You may qualify if:

• Be able to give written IRB approved informed consent and be able to follow protocol requirements.
• Be greater than or equal to 18 years of age on day of signing informed consent.
• Has a performance status of 0 or 1 on the ECOG Performance Scale
• Has histologically confirmed urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible. Pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded.
• Has clinical stage T2-T4a N0/X M0 urothelial carcinoma. Clinical T stage is based on the pre-study standard of care transurethral resection of the bladder tumor (TURBT) sample and imaging studies.
• Has staging scans with abdominal/pelvic CT or MRI scan and CT scan or x-ray of the chest within 4 weeks prior to treatment initiation
• Be a medically appropriate candidate for radical cystectomy as determined by an attending urologist and be planning to receive cystectomy.
• Has had no prior systemic cytotoxic chemotherapy for urothelial carcinoma (prior intravesicular chemotherapies are permitted)
• Patients must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission that is sufficient for correlative testing, and agree to submission of a paraffin block or 20 formalin-fixed paraffin embedded (FFPE) slides of 5-10 microns in thickness. Patients must also agree to submission of tissue from cystectomy.
• Demonstrate adequate organ function as defined in the table below; all screening labs should be performed within 10 days of treatment initiation.
• Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculated creatinine clearance (CrCL; GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR
• ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (Creatinine clearance should be calculated per CKD-EPI equation.) Hepatic Serum total bilirubin ≤ 1.5 X ULN (≤ 3 X ULN if Gilbert's Syndrome) OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy. If subject receiving anticoagulants, PT or PTT should be within therapeutic range of intended use of anticoagulants
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of pembrolizumab.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. The two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. Subjects should start using birth control from the screening visit and continue throughout the study period up to 120 days after the last dose of study therapy.

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject meets any of the following:
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of pembrolizumab.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. NOTE: see exception to use of systemic steroid as prophylactic anti-emetic prior to cisplatin in section 4.2.2. Inhaled and topical steroids are allowed.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 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 had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (2)

North Carolina Cancer Hospital (UNC)

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Rose TL, Harrison MR, Deal AM, Ramalingam S, Whang YE, Brower B, Dunn M, Osterman CK, Heiling HM, Bjurlin MA, Smith AB, Nielsen ME, Tan HJ, Wallen E, Woods ME, George D, Zhang T, Drier A, Kim WY, Milowsky MI. Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. J Clin Oncol. 2021 Oct 1;39(28):3140-3148. doi: 10.1200/JCO.21.01003. Epub 2021 Aug 24.

  PMID: 34428076 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

pembrolizumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Robin V. Johnson
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

robin_v_johnson@med.unc.edu

919-966-1125

Study Officials

• Matthew I Milowsky, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 24, 2016
• Study Start: May 1, 2016
• Primary Completion: July 6, 2020
• Study Completion: January 30, 2026
• Last Updated: March 20, 2026
• Results First Posted: August 10, 2021

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)