Evaluating Immune Therapy, Durvalumab (MEDI4736) With Tremelimumab for Metastatic, Non-transitional Cell Carcinoma of the Urinary Tract

NCT03430895 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 17-511
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

This study is being done test to test the safety and effectiveness of durvalumab combined with tremelimumab in patients who have a rare form of cancer of the urinary tract.

Conditions

Non-Transitional Cell Carcinoma of the Urothelial Tract; Small Cell of the Bladder; Adenocarcinoma of the Bladder; Squamous Cell Carcinoma of the Bladder; Metastatic Bladder Cancer

Keywords

Durvalumab (MEDI4736); Tremelimumab; immunotherapy; 17-511

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  by RECIST 1.1

  2 years

Study Arms (1)

combination of durvalumab and tremelimumab

EXPERIMENTAL

Patients will receive durvalumab 1500 mg and tremelimumab 75 mg IV Q4W for up to 4 doses/cycles, then durvalumab 1500 mg Q4W starting at Week 16 for 9 doses (total treatment duration of 12 months).

Drug: durvalumab and tremelimumab

Interventions

durvalumab and tremelimumab DRUG

Patients will receive durvalumab 1500 mg and tremelimumab 75 mg IV Q4W for up to 4 doses/cycles, then durvalumab 1500 mg Q4W starting 4 weeks after the last combination treatment for up to 9 doses.

combination of durvalumab and tremelimumab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at time of informed consent
• Body weight \> 30 kg
• Histologically or cytologically confirmed small cell carcinoma, squamous cell carcinoma or adenocarcinoma (confirmed at MSKCC) of the bladder, ureter, urethra, urachus, or renal pelvis. Patients with squamous cell carcinoma and adenocarcinoma are required to have a predominant squamous or adenocarcinoma component as reviewed by the pathologist at MSKCC. However, if any element of small cell or neuroendocrine differentiation is present, the patients will be classified as small cell/neuroendocrine.
• Confirmation of availability of sufficient tissue from a prior surgery for correlative studies is required prior to enrollment. Patients must have representative non-TCC or the urothelial tract FFPE archival tumor specimens (tumor blocks or 30 unstained slides; preference for tumor blocks). These samples may be submitted between the time of consent and the start of treatment. Patients with \< 30 slides may be enrolled after discussion with the principal or co-principal investigators.
• Clinical evidence of metastatic (T4b, any N; any T, N2-3; M1) disease.
• Life expectancy of 12 weeks of greater based on assessment by the treating investigator.
• Evidence of measurable disease by RECIST 1.1.
• Patients with small cell carcinoma must have progressed after at least one prior systemic therapy. Patients with squamous cell carcinoma or adenocarcinoma may be previously untreated or have progressed after prior systemic therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen. NOTE: There is no maximum number of prior treatments allowed.
• Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. Subjects with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (\> 1000 per mm\^3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm\^3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (≤ 3 x institutional ULN in patients with Gilbert"s syndrome)

You may not qualify if:

• Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the last 14 days
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia"s Correction
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) \< 21 days prior to enrollment.
• Major surgery within 28 days of starting study treatment. There is no minimum time requirement for minor procedures such as biopsy or vascular access placement.
• Radiation within 14 days of starting study treatment
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Any unresolved toxicity from previous anti-cancer therapy must have resolved to at least ≤ Grade 1 (or baseline) at time of enrollment.
• Patients with irreversible toxicity that is not reasonably expected to be exacerbated by treatment with durvalumab and tremelimumab may be included after consultation with the Principal Investigator or Co-Principal Investigator (e.g. alopecia, hearing loss, peripheral neuropathy).
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis, celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (4)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memoral Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

durvalumab; tremelimumab

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

Results Point of Contact

• Title: Dr. Samuel Funt, MD
• Organization: Memorial Sloan Kettering Cancer Center

funts@mskcc.org

646-888-4770

Study Officials

• Samuel Funt, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: This is a single-arm, phase II study with a Simon minimax design testing the combination of durvalumab and tremelimumab in patients with non-TCC of the urothelial tract.

Study Record Dates

• First Submitted: February 7, 2018
• First Posted: February 13, 2018
• Study Start: January 31, 2018
• Primary Completion: February 10, 2021
• Study Completion: February 10, 2021
• Last Updated: December 1, 2021
• Results First Posted: December 1, 2021

Record last verified: 2021-02

Locations

US (4)