Radiation Therapy and Pembrolizumab in Treating Patients With Localized Urothelial Bladder Cancer

NCT03419130 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: 17522NCI-2017-0219617-22452
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial studies how well radiation therapy and pembrolizumab work in treating patients with urothelial bladder cancer that is restricted to the site of origin, without evidence of spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving radiation therapy and pembrolizumab may work better in treating urothelial bladder cancer.

Conditions

Infiltrating Bladder Urothelial Carcinoma; Stage II Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (3)

• cCR rate (expansion cohort)

  A complete response will be defined as the absence of visible tumor endoscopically (cystoscopically) and the absence of histologic evidence of disease if a biopsy is performed.

  Up to 24 months

• Clinical complete response (cCR) rate (safety lead-in)

  A cCR rate will be defined at week 12 after the initiation of study therapy as no residual muscle-invasive disease (=\< T1) on cystoscopy. This rate will be summarized using descriptive statistics. The point estimate of cCR rate will be obtained with its 95% confidence intervals.

  At 12 weeks

• Incidence of adverse events evaluated according to Common Terminology Criteria for Adverse Events version 4.3 (safety lead-in)

  Safety will be summarized using descriptive statistics.

  Up to 12 weeks

Secondary Outcomes (8)

• Disease specific survival (DSS)

  At 6 months

• Distant metastasis free survival (DMFS)

  At 6 months

• DMFS

  At 12 months

• DSS

  At 12 months

• Incidence of adverse events evaluated according to CTCAE version 4.3

  Up to 24 months

Study Arms (2)

Cohort I (pembrolizumab, hypofractionated RT)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 13 courses in the absence of disease progression or unacceptable toxicity. Patients also receive hypofractionated RT over 5 fractions for 14 days.

Radiation: Hypofractionated Radiation Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Cohort II (pembrolizumab, conventionally fractionated RT)

EXPERIMENTAL

Patients receive pembrolizumab as in Cohort I. Patients also receive conventionally fractionated RT over 30 fractions for 52 weeks.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Radiation: Radiation Therapy

Interventions

Hypofractionated Radiation Therapy RADIATION

Undergo hypofractionated RT

Also known as: Hypofractionated Radiotherapy, hypofractionation

Cohort I (pembrolizumab, hypofractionated RT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Cohort I (pembrolizumab, hypofractionated RT); Cohort II (pembrolizumab, conventionally fractionated RT)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Cohort I (pembrolizumab, hypofractionated RT); Cohort II (pembrolizumab, conventionally fractionated RT)

Radiation Therapy RADIATION

Undergo conventionally fractionated RT

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Cohort II (pembrolizumab, conventionally fractionated RT)

Eligibility Criteria

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

You may qualify if:

• Localized, muscle invasive urothelial carcinoma (T2-4, N0-1, M0) (mixed histology acceptable) ineligible for cystectomy
• Patients must not be suitable for concurrent cisplatin as determined by the following:
• Creatinine clearance less than 60ml/min; glomerular filtration rate (GFR) should be assessed by calculation from serum/plasma creatinine (Cockcroft-Gault formula)
• Common Terminology Criteria for Adverse Events (CTCAE) grade (Gr) \>= 2 hearing loss
• CTCAE Gr \>= 2 neuropathy
• Patients must not be suitable for fluorouracil (5FU)/mitomycin chemotherapy
• Subjects with not meeting the above criteria are still eligible provided the patient declines concurrent chemotherapy with radiation, after specific informed consent describing the known benefits of adding chemotherapy to the definitive bladder radiation regimen; the reason for declining must be documented
• Life expectancy of at least 3 months or greater
• Be willing and able to provide written informed consent/assent for the trial
• Be willing to provide tissue from a newly obtained transurethral resection of bladder tumor (TURBT) or biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to 8 weeks (56 days) prior to initiation of treatment on say 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor
• Have a performance status of 0 - 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>= 1,500 /mcL, performed within 28 days of treatment initiation
• Platelets \>= 100,000 / mcL, performed within 28 days of treatment initiation
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment), performed within 28 days of treatment initiation
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 30 mL/min for subject with creatinine levels \> 1.5 X institutional ULN, performed within 28 days of treatment initiation

You may not qualify if:

• Non-muscle invasive, localized bladder cancer (Tis, Ta, T1)
• Presence of distant metastatic disease or disease not amenable to radiation treatment
• Prior radiation treatment to the pelvis
• Prior cystectomy
• Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks of the first dose of treatment
• 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 a known history of active tuberculosis (TB) (Mycobacterium tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) 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
• Prior systemic chemotherapy for bladder cancer; prior intravesical chemotherapy for the treatment of non-muscle invasive urothelial bladder cancer (UBC) is allowed
• Upper tract urothelial carcinoma
• Has had prior chemotherapy or targeted small molecule 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 or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer

Sponsors & Collaborators

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

Study Sites (1)

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

MeSH Terms

Interventions

Radiation Dose Hypofractionation; pembrolizumab; Radiotherapy; Radiation

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Therapeutics; Physical Phenomena

Study Officials

• Terence Friedlander

  UCSF Medical Center-Mount Zion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: February 1, 2018
• Study Start: July 18, 2018
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2022
• Last Updated: December 7, 2018

Record last verified: 2018-12

Locations

US (1)