Trial of Tremelimumab in Patients With Previously Treated Metastatic Urothelial Cancer

NCT03557918 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN GU17-294
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 7

Brief Summary

This is a phase II trial designed to estimate the activity of single agent tremelimumab in subjects with metastatic urothelial cancer with disease progression despite prior treatment with PD-1/PD-L1 blockade. The primary endpoint is objective response rate and the study will employ a Simon's 2-stage design.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1.

  Up to a maximum of 12 months

Secondary Outcomes (5)

• Adverse Events

  AE had been recorded from time of consent until 30 days after discontinuation of study drug or until a new anti-cancer treatment starts, whichever occurs first; up to a maximum of 13 months

• Disease Control Rate

  Up to a maximum of 12 months

• Duration of Response

  Up to a maximum of 24 months

• Progression Free Survival (PFS)

  Time of treatment start until the criteria for disease progression or death. Up to a maximum of 24 months.

• Overall Survival

  Time of treatment start until death or date of last contact, up to a maximum of 42 months.

Study Arms (1)

Tremelimumab

EXPERIMENTAL

Tremelimumab 750 mg IV Day 1 of each 28 day cycle. Up to 7 cycles.

Drug: Tremelimumab

Interventions

Tremelimumab DRUG

Tremelimumab 750 mg IV on Day 1 of each 28 day cycle; up to 7 cycles. Subjects that complete all initial 7 cycles but later progress during follow up may receive an additional 7 cycles of tremelimumab providing they meet eligibility criteria.

Tremelimumab

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• ECOG Performance Status of 0 or 1 within 14 days prior to registration.
• Histologically or cytologically documented urothelial cancer. Locally advanced (T4b, any N; or any T, N 2-3) or metastatic disease (M1, Stage IV) (also termed TCC or UCC of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra). Subjects with mixed histologies are eligible provided that the predominant component is urothelial cancer. Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera (clinical Stage T4b) or bulky nodal metastasis (N2-N3).
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or at least 15 unstained slides. If archival tissue is not available and the subject is undergoing a standard of care biopsy, tissue from the biopsy is required to be submitted for correlative analyses. Subjects without adequate baseline tumor tissue may be considered for enrollment on a case by case basis after discussion with the sponsor-investigator.
• Measurable disease according to RECIST 1.1 within 28 days prior to registration. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with computed tomography (CT) (preferred) or magnetic resonance imaging (MRI) scans, preferably with IV contrast, and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines; lesions in a previously irradiated field can be used as a measurable disease provided that there has been demonstrated progression in the lesion.
• A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic
• Subjects must have progressed despite prior treatment with anti-PD-1/PD-L1 antibody therapy. In addition, subjects must meet the following criteria:
• Subjects must not have progressed within 2 months of starting prior anti-PD-1/PD-L1 antibody therapy.
• Subjects must have received at least 1 line of prior systemic therapy
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study with the exception of endocrine related AEs that are stable on replacement therapy (e.g., steroids, thyroid hormone) which may be considered eligible but must be discussed with the sponsor-investigator.
• Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic (neuro-muscular) or ocular AE of any grade while receiving prior immunotherapy. NOTE: Subjects with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic. Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
• Patients with Gr 3 AST/ALT elevation \< 8 fold that resolved with steroids without additional immunosuppression can be included (Patients who experienced Hy's law on PD-1/L1 therapy will be excluded)
• Prior cancer treatment must be completed at least 28 days or 5 half-lives (whichever is shorter) prior to first dose of study drug. Subjects must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline.
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration.

You may not qualify if:

• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Known additional malignancy that is active and/or progressive requiring treatment. Patients with incidental histologic findings of prostate cancer (tumor/node/metastasis stage of T1a or T1b or prostate-specific antigen \<10) who have not received hormonal treatment may be included, pending a discussion with the sponsor-investigator
• Treatment with any investigational drug within 28 days prior to registration.
• Prior treatment with an anti-CTLA-4 antibody
• Subjects with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Sponsor Investigator
• Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with tremelimumab (e.g., hearing loss) may be included after consultation with the sponsor-investigator
• Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable (e.g., local surgery or radiotherapy)
• Radiation therapy within 14 days of first dose of study drug
• Major surgical procedure within 28 days prior to first dose of study treatment
• History of allogeneic organ transplantation that requires use of immunosuppressive agents
• Active or prior documented autoimmune of inflammatory disorders (including but not limited to inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc). The following are exceptions to this criterion:
• Subjects with vitiligo
• Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Subjects without active disease in the last5 years may be considered for enrollment after discussion with the sponsor-investigator

Sponsors & Collaborators

• Matthew Galsky: lead
• AstraZeneca: collaborator

Study Sites (7)

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Westwood, Kansas, 66205, United States

Location

Dana Farber- Partners Cancer Care, Inc

Boston, Massachusetts, 02215, United States

Location

Ichan School of Medicine at Mount Sinai

New York, New York, 10029-6542, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Huntsman Cancer Institute University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Miller EJ, Rose TL, Maughan BL, Milowsky MI, Bilen MA, Carthon BC, Gao X, Rapisuwon S, Zhao Q, Yu M, Agarwal N, Galsky MD. Phase 2 trial of tremelimumab in patients with metastatic urothelial cancer previously treated with programmed death 1/programmed death ligand 1 blockade. Cancer. 2024 May 1;130(9):1642-1649. doi: 10.1002/cncr.35179. Epub 2024 Jan 5.

  PMID: 38180804 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

tremelimumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Matthew D Galsky, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: Single group assignment

Study Record Dates

• First Submitted: June 5, 2018
• First Posted: June 15, 2018
• Study Start: November 12, 2018
• Primary Completion: December 6, 2021
• Study Completion: June 7, 2023
• Last Updated: July 3, 2024
• Results First Posted: July 3, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)