Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Hydronephrosis

Urethral Neoplasms

Ureteral Neoplasms

Pelvic Neoplasms

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urethral Diseases

Urologic Diseases

Male Urogenital Diseases

Kidney Diseases

Ureteral Diseases

Transitional Cell Carcinoma

Urethral Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Cisplatin

Durvalumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Tremelimumab

Ipilimumab

Antineoplastic Agents, Immunological

Immunologic Factors

Immune Checkpoint Inhibitors

Patients receive tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1 of weeks 1 and 4. Beginning 4-6 weeks after the last infusion, patients undergo cystectomy with pelvic lymph node dissection surgery.

Undergo cystectomy with pelvic lymph node dissection

Therapeutic Conventional Surgery

Jianjun Gao

This pilot phase I trial studies the side effects of durvalumab and tremelimumab in treating patients with muscle-invasive, high-risk urothelial cancer that cannot be treated with cisplatin-based therapy before surgery. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of durvalumab and tremelimumab in patients with muscle-invasive, high-risk bladder cancer who are ineligible for neoadjuvant cisplatin-containing chemotherapies.

SECONDARY OBJECTIVES:

I. To assess immunologic/molecular responses (e.g. peripheral blood cluster of differentiation \[CD\] 4+inducible T-cell co-stimulator \[ICOS\]+ T cells) to durvalumab and tremelimumab in patients with muscle-invasive, high-risk bladder cancer who are ineligible for neoadjuvant cisplatin-containing chemotherapies.

II. To evaluate pathologic T0 rate after neoadjuvant treatment with durvalumab and tremelimumab in patients with muscle-invasive, high-risk bladder cancer comparing to historical data (about 10% in patients with high-risk disease).

III. To evaluate relapse-free survival (RFS) and overall survival (OS).

OUTLINE:

Patients receive tremelimumab intravenously (IV) over 1 hour and durvalumab IV over 1 hour on day 1 of weeks 1 and 4. Beginning 4-6 weeks after the last infusion, patients undergo cystectomy with pelvic lymph node dissection surgery.

After completion of study treatment, patients are followed up at 90 days, and then every 3 months for up 1 year.

Durvalumab and Tremelimumab in Treating Patients With Muscle-Invasive, High-Risk Urothelial Cancer That Cannot Be Treated With Cisplatin-Based Therapy Before Surgery

A Pilot Pre-Surgical Study Evaluating Anti-PD-L1 Antibody (Durvalumab) Plus Anti-CTLA-4 (Tremelimumab) in Patients With Muscle-Invasive, High-Risk Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Neoadjuvant Chemotherapy

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Micronutrients

Hematinics

Vitamins

Pemetrexed

Avelumab

Folic Acid Antagonists

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folinic Acid

Folate

Vitamin B9

Patients receive pemetrexed IV over 10 minutes on day 1. Starting cycle 2, patients also receive avelumab IV over 60 minutes. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Amishi Y Shah

This phase II trial studies how well pemetrexed and avelumab work in treating patients with MTAP-deficient urothelial cancer that has spread to other places in the body. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pemetrexed and avelumab may work better in treating patients with MTAP-deficient urothelial cancer.

PRIMARY OBJECTIVES:

I. To evaluate the response rate (RR) in patients with (methylthioadenosine phosphorylase) MTAP-deficient metastatic urothelial cancer treated sequentially with pemetrexed and avelumab.

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) and overall survival (OS) in patients with MTAP-deficient metastatic urothelial cancer treated sequentially with pemetrexed and avelumab.

II. To explore the effect of pemetrexed +/- avelumab on the immune system and tumor microenvironment including peripheral T-cells, tumor-infiltrating T-cells, macrophages, and myeloid-derived suppressor cells (MDSCs).

OUTLINE:

Patients receive pemetrexed intravenously (IV) over 10 minutes on day 1. Starting cycle 2, patients also receive avelumab IV over 60 minutes. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 120 days, and then every 3 months for 2 years.

Pemetrexed and Avelumab in Treating Patients With MTAP-Deficient Metastatic Urothelial Cancer

A Phase II Trial to Evaluate Combination Therapy With Pemetrexed and Avelumab in Previously Treated Patients With MTAP-Deficient Advanced Urothelial Cancer

Will be defined as the number of subjects with a best response of complete response or partial response at any protocol evaluation by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria divided by the total numbers of subjects receiving their first dose of trial therapy.

Will be presented using Kaplan-Meier estimates.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Durvalumab and Tremelimumab in Treating Patients With Muscle-Invasive, High-Risk Urothelial Cancer That Cannot Be Treated With Cisplatin-Based Therapy Before Surgery	NCT02812420	Hydronephrosis Infiltrating Bl... Infiltrating Bl... Infiltrating Bl... Infiltrating Re... Renal Pelvis Ur... Stage II Bladde... Stage II Renal ... Stage II Ureter... Stage II Urethr... Stage III Bladd... Stage III Renal... Stage III Urete... Stage III Ureth... Stage IV Renal ... Stage IV Ureter... Stage IV Urethr... Ureter Urotheli... Urethral Urothe...	Durvalumab Therapeutic Con... Tremelimumab	18 Years -	M.D. Anderson Cancer Center
Pemetrexed and Avelumab in Treating Patients With MTAP-Deficient Metastatic Urothelial Cancer	NCT03744793	Infiltrating Bl... Infiltrating Bl... Infiltrating Bl... Infiltrating Bl... Infiltrating Bl... Metastatic Urot... MTAP Negative	Avelumab Pemetrexed	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for infiltrating bladder urothelial carcinoma sarcomatoid variant