Pembrolizumab and Docetaxel or Gemcitabine Hydrochloride in Treating Patients Urothelial Cancer

NCT02437370 | Completed Phase 1 DMC

• 4 other identifiers: 723260UCDCC#25251521NCI-2015-00426
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of pembrolizumab when given together with docetaxel or gemcitabine hydrochloride in treating patients with previously treated urothelial cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or that has spread from the primary site (place where it started) to other places in the body (metastatic). Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as docetaxel and gemcitabine hydrochloride, 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 together with docetaxel or gemcitabine hydrochloride may be a better treatment for urothelial cancer.

Conditions

Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Regional Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage III Bladder Urothelial Carcinoma; Stage III Urethral Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Urethral Cancer; Urethral Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of pembrolizumab based on the incidence of dose limiting toxicity, defined as the Incidence of adverse events, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Will be summarized descriptively by tables of numbers and percent of patients experiencing adverse events, overall and by type, grade, seriousness, duration, action taken, and assessment of relation to pembrolizumab or docetaxel or gemcitabine hydrochloride.

  Up to 6 months post-treatment

Secondary Outcomes (3)

• Overall response rate (ORR), assessed using the RECIST version 1.1

  Up to 6 months post-treatment

• Progression free survival (PFS)

  Time from enrollment to the first occurrence of disease progression, as determined by RECIST v1.1, or death from any cause, assessed up to 6 months post-treatment

• PD-L1 expression

  Baseline

Study Arms (2)

Arm A (pembrolizumab, docetaxel)

EXPERIMENTAL

pembrolizumab IV over 30 minutes on day 1 and docetaxel IV over 60 minutes on day 1.

Drug: Pembrolizumab; Drug: Docetaxel

Arm B (pembrolizumab, gemcitabine hydrochloride)

EXPERIMENTAL

pembrolizumab IV as in Arm A and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8.

Drug: Pembrolizumab; Drug: Gemcitabine Hydrochloride

Interventions

Pembrolizumab DRUG

Given IV

Also known as: Keytruda, MK-3475

Arm A (pembrolizumab, docetaxel); Arm B (pembrolizumab, gemcitabine hydrochloride)

Docetaxel DRUG

Given IV

Arm A (pembrolizumab, docetaxel)

Gemcitabine Hydrochloride DRUG

Given IV

Arm B (pembrolizumab, gemcitabine hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Have locally advanced or metastatic urothelial cancer that is not amenable to curative surgical treatment
• Have histologically or cytologically confirmed urothelial tract carcinoma
• Be previously chemotherapy-treated; all patients may have received up to two prior lines of chemotherapy (excludes systemic therapy) for recurrent/advanced disease, as long as one of those regimens was platinum-based; (it is anticipated that patients would have been previously treated with MVAC or GC, or variations of these standard frontline regimens)
• Be willing and able to provide written informed consent for the trial
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
• Life expectancy of greater than 6 months
• Have a performance status of 0 to 1 on the Zubrod performance scale
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated\* creatinine clearance \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN; (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\])
• Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases

You may not qualify if:

• 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 treatment
• Has known hypersensitivity to MK-3475 (pembrolizumab) or any of its incipients
• Patients with a known hypersensitivity to gemcitabine (Arm B only)
• Patients with hypersensitivity to docetaxel or polysorbate 80 (Arm A only)
• 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
• 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: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• 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; free of disease for more than 5 years
• 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 the first dose of trial treatment 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 to trial treatment
• Has an 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; anti-coagulants are permitted
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis
• Has an active serious bacterial infection requiring systemic antimicrobial 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

Sponsors & Collaborators

• University of California, Davis: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Urethral Neoplasms

Interventions

pembrolizumab; Docetaxel; Gemcitabine

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; Urethral Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Primo Lara

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: May 7, 2015
• Study Start: September 1, 2015
• Primary Completion: August 7, 2019
• Study Completion: March 10, 2020
• Last Updated: October 18, 2022

Record last verified: 2022-10

Locations

US (1)