Checkpoint Inhibitor and Radiation Therapy in Bulky, Node-Positive Bladder Cancer

NCT04779489 | Terminated Results DMC FDA Device

• 1 other identifier: STU-2021-0114
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Clinically node positive (cN+) bladder cancer carries a poor prognosis, especially in patients who are unable to receive or fail to respond to neoadjuvant chemotherapy. Immune checkpoint inhibitor (ICI) therapy is FDA-approved in advanced bladder cancer for patients unable to receive or failing to respond to platinum-based chemotherapy. The present study seeks to determine if next-generation radiation therapy (personalized ultrafractionated stereotactic ablative radiotherapy, or PULSAR) is feasible and effective in patients receiving ICI for bulky cN+ bladder cancer.

Conditions

Bladder Cancer

Keywords

bladder cancer; lymph node metastasis; immunotherapy; radiation therapy

Outcome Measures

Primary Outcomes (1)

• Protocol Completion

  proportion of patients completing PULSAR and undergoing radical cystectomy

  16 weeks

Secondary Outcomes (1)

• Progression-free Survival

  2 years

Other Outcomes (7)

• Major Complication Rate

  90 days

• Pathologic Complete Response

  at time of radical cystectomy

• Pathologic Non-muscle Invasive Downstaging

  at time of radical cystectomy

Study Arms (1)

PULSAR

EXPERIMENTAL

Eligible patients will receive next-generation stereotactic radiotherapy (PULSAR) 30-36 Gy in 3 fractions to the bladder and targetable, pathologically enlarged lymph nodes

Radiation: personalized ultrafractionated stereotactic ablative radiotherapy

Interventions

personalized ultrafractionated stereotactic ablative radiotherapy RADIATION

next-generation stereotactic ablative radiotherapy to bladder and enlarged lymph nodes

Also known as: PULSAR

PULSAR

Eligibility Criteria

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

You may qualify if:

• Bladder cancer, confirmed pathologically on transurethral resection of bladder tumor (TURBT) or on bladder biopsy. Pure urothelial, variant urothelial, or any proportion of squamous cell carcinoma are permitted. Questions about eligibility may be resolved by consultation with UTSW pathology but formal pathologic review is not required.
• Bulky, clinically node positive disease (cN+) defined as: 1) a single pelvic lymph node of ≥ 1.5 cm largest diameter on CT or MRI; or 2) multiple pelvic lymph nodes ≥ 1 cm largest diameter on CT or MRI. Pathologic confirmation is not required. Imaging to establish eligibility must have been obtained no more than 60 days prior to trial enrollment. The scans must be personally reviewed by the enrolling clinician. For imaging studies obtained outside of UT Southwestern, imaging review of node status and sign off by the enrolling investigator is required. Review and sign off by a UTSW radiologist is optional in ambiguous or questionable cases, but is not mandatory.
• Age ≥ 18 years.
• ECOG performance status 0-1.
• Appropriate candidate for radical cystectomy, as determined by the treating urologist.
• Appropriate candidate for stereotactic ablative radiotherapy, as determined by the treating radiation oncologist.
• Patient is planned to initiate or is within 1-3 weeks of initiation of FDA-approved immune checkpoint inhibitor therapy based on ineligibility to receive platinum-based downstaging chemotherapy (DCT) (Cohort 1, as detailed below) or failure to achieve clinical complete response to platinum-based DCT (Cohort 2, as detailed below).
• Cohort 1 (chemotherapy-ineligible) - either of:
• patient staged with bulky cN+ disease as defined above, medically ineligible to receive any platinum-based chemotherapy or, after appropriate and documented counseling, refusing to receive any-platinum-based chemotherapy; or
• patient staged with bulky cN+ disease as defined above, medically ineligible to receive cisplatin-based chemotherapy, with PD-L1 positive tumor (according to methodology described in the FDA approval label for the respective ICI agent)
• Cohort 2 (chemotherapy non-responding) - any of:
• patient, initially staged with bulky cN+ disease as defined above, with radiologic progression after two cycles of platinum-based DCT (per RECIST 1.1 criteria: ≥20% increase in summed short-axis diameter of visible lesions with ≥ 5 mm absolute increase)
• patient, initially staged with bulky cN+ disease as defined above, failing to achieve radiologic complete response after three or four cycles of platinum-based DCT (failure of all enlarged lymph nodes to decrease to \< 1 cm short-axis diameter)
• patient, initially staged with bulky cN+ disease as defined above, failing to achieve radiologic complete response after one or two cycles of platinum-based DCT which was discontinued due to patient intolerance
• patient, initially not staged with bulky cN+ disease as defined above, who progresses to cN+ disease as defined above after two or more of cycles of platinum-based DCT

You may not qualify if:

• Medical or anatomic contraindication to any of the study treatment modalities (radical cystectomy, stereotactic ablative radiotherapy, immune checkpoint inhibitor therapy).
• Non-urothelial histology (other than pure squamous cell, which is permitted) including pure adenocarcinoma, pure small cell carcinoma, sarcoma, lymphoma, non-genitourinary primary (e.g. colorectal).
• Metastatic (cM1) disease, defined as 1) lymph nodes ≥ 1 cm above the aortic bifurcation (cM1a), or metastases to bone, brain, or any visceral site (cM1b). Patients with a single enlarged retroperitoneal lymph node will be eligible with an adequately performed lymph node biopsy showing no metastatic disease or with a PET scan showing absence of FDG avidity.
• Second primary malignancy, except: 1) non-metastatic (cM0) prostate cancer, 2) non-metastatic (cM0) endometrial cancer, 3) non-melanoma skin cancer, 4) cervical squamous cell carcinoma in situ, 4) any AJCC Stage I/II or organ-confined primary malignancy for which the patient has undergone curative treatment and has been without evidence of disease for three years.
• Prior pelvic radiation therapy.
• Autoimmune disease rendering the patient ineligible for ICI.
• Treatment with any immunosuppressive agent within 14 days of study entry, excluding topical or inhaled corticosteroids or adrenal-replacement steroids.
• End stage renal disease requiring dialysis.
• HIV infection, unless stable on HAART with CD4+ count \> 400.
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab, avelumab, durvalumab, nivolumab, pembrolizumab, or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than atrial fibrillation / atrial flutter), or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Lymphatic Metastasis

Interventions

DEAE-Dextran

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; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dextrans; Glucans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Dr. Solomon Woldu
• Organization: UT Southwestern Medical Center

solomon.woldu@utsouthwestern.edu

214-648-9558

Study Officials

• Solomon L Woldu, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Urology

Model Details: single-arm interventional study

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: March 3, 2021
• Study Start: September 6, 2021
• Primary Completion: June 2, 2023
• Study Completion: June 2, 2023
• Last Updated: February 6, 2024
• Results First Posted: August 22, 2023

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)