A Phase II Multicenter Study of Chemotherapy Versus Chemotherapy Plus Durvalumab (MEDI 4736) in Patients With Lymph Node Positive Urothelial Carcinoma of the Bladder

NCT05137262 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-1091NCI-2021-12884
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase II randomized study of standard of care (SOC) neo-adjuvant cisplatin chemotherapy (NAC) versus NAC plus durvalumab in patients with either clinical or pathologic intra-pelvic node-positive urothelial carcinoma of the bladder. Patients with cTanyN1-3M0 via American Joint Committee on Cancer (AJCC) 8th edition staging30 will be considered tor enrollment in this trial. We plan to enroll 60 patients. Patients will be randomized 2:1 to the intervention arm with durvalumab plus NAC vs SOC NAC. In patients randomized to receive, durvalumab will be continued as maintenance every 4 weeks until either relapse or 1 year, whichever event occurs first. Tissue collection will occur as a biopsy prior to initiation of neo-adjuvant therapy via both transurethral biopsy of bladder and lymph node biopsy. Tissue will again be collected at the time of radical cystectomy or, in patients who are no longer surgical candidates, in the form of biopsy as standard of care. Blood and urine will be collected at baseline, week 2, week 6, week 16, and at the 6 week-post surgery visit for analysis of correlative studies.

Conditions

Urothelial Carcinoma; Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• To estimate the difference in the pathologic complete response rate.

  through study completion, an average of 1 year

Study Arms (2)

Arm A: Standard of Care with dose-dense MVAC

EXPERIMENTAL

The patient will receive treatment every 14 days for up to 6 cycles in the neoadjuvant setting.

Other: Abiraterone acetate; Drug: Durvalumab; Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin Hydrochloride; Drug: Cisplatin

Arm B: Intervention with dose-dense MVAC plus Durvalumab

EXPERIMENTAL

Durvalumab will be administered one week prior to the initial cycle of dose-dense MVAC and then with each additional cycle of dose-dense MVAC on Arm B

Other: Abiraterone acetate; Drug: Durvalumab; Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin Hydrochloride; Drug: Cisplatin

Interventions

Abiraterone acetate OTHER

Given by IV

Also known as: Zytiga™

Arm A: Standard of Care with dose-dense MVAC; Arm B: Intervention with dose-dense MVAC plus Durvalumab

Durvalumab DRUG

Given by IV

Also known as: MEDI4736

Arm A: Standard of Care with dose-dense MVAC; Arm B: Intervention with dose-dense MVAC plus Durvalumab

Methotrexate DRUG

Given by IV

Arm A: Standard of Care with dose-dense MVAC; Arm B: Intervention with dose-dense MVAC plus Durvalumab

Vinblastine DRUG

Given by IV

Also known as: Velban

Arm A: Standard of Care with dose-dense MVAC; Arm B: Intervention with dose-dense MVAC plus Durvalumab

Doxorubicin Hydrochloride DRUG

Given by IV

Also known as: Adriamycin RDF™, Adriamycin PFS®, Adriamycin®, Rubex®

Arm A: Standard of Care with dose-dense MVAC; Arm B: Intervention with dose-dense MVAC plus Durvalumab

Cisplatin DRUG

Given by IV

Also known as: Platinol®-AQ, Platinol®, CDDP

Arm A: Standard of Care with dose-dense MVAC; Arm B: Intervention with dose-dense MVAC plus Durvalumab

Eligibility Criteria

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

You may qualify if:

• Patients must have histological diagnosis of urothelial carcinoma of the bladder and must meet criteria for stage cTanyN1-3M0 disease via AJCC 8th edition staging criteria30
• Patients must provide tissue by agreeing to transurethethral biopsy of the bladder and the lymph node prior to initiating treatment. If patient is unable or unwilling to undergo biopsy at screening and tissue is available, patient may be eligibile per PI discretion.
• Patients must be ≥18 years of age.
• Patients must have pelvic lymph node amenable for biopsy as assessed by treating MD and interventional radiologist.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Patients must have a life expectancy of at least 12 weeks.
• Patients must have body weight \>30 kg.
• Left ventricular ejection fraction ≥ 50%.
• Adequate organ function as defined below:
• Hematological i. Absolute neutrophil count (ANC) ≥ 1,500/mcL. ii. Platelets ≥100,000 / mcL. iii. Hemoglobin ≥9 g/dL
• Renal iv. Creatinine clearance \> 50 ml/min as calculated by the Cockgroft Gault formula as:
• \. CLCR = {\[(140-age) × weight)\]/(72 x SCR) × 0.85 (if female), where CLCR (creatinine clearance) is measured in mL/min, age is expressed in years, weight in kilograms (kg), and SCR (serum creatinine) in mg/dL.
• Hepatic v. Serum total bilirubin ≤1.5xULN OR Direct bilirubin ≤ULN for subjects with total bilirubin levels \>1.5xULN. vi. AST and ALT ≤2.5xULN OR ≤5xULN for subjects with liver metastases.
• Coagulation vii. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. viii. Activated Partial Thromboplastin Time (aPTT) ≤1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• Women of child-bearing potential MUST have a negative serum or urine HCG test unless prior tubal ligation (\>/= 1 year before screening), total hysterectomy or menopause (defined as 12 consecutive months of amenorrhea). Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use dual contraception for the duration of study participation and for 90 days after receipt of last drug on active treatment.

You may not qualify if:

• Has metastatic disease to lymph nodes outside of the pelvis or to visceral sites as seen on imaging.
• CTCAE v5.0 Grade ≥ 2 neuropathy.
• CTCAE v5.0 Grade ≥ 2 hearing loss.
• New York Heart Association (NYHA) Class III or IV heart failure defined as:
• Class III heart failure is defined as: patients with cardiac disease resulting in marked limitation of physical activity and/or less than ordinary activity causes fatigue. Patients are comfortable only at rest.
• Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases
• Known active Hepatitis B, Hepatitis C infection (HCV-DNA positive), or HIV infection.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from chemotherapy and/or immunotherapy delivered as part of the therapy on trial is allowed.
• Prior exposure to any anti-PD-1 or anti-PD-L1 (including durvalumab) antibody.
• Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• History of primary immunodeficiency.
• History of allogeneic organ transplant.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
• Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
• Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization. Minor infections, e.g. periodontal infection or urinary tract infection (UTI), which may be treated with short-term oral antibiotics are allowed.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (2)

Indiana University

Bloomington, Indiana, 47405, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center website

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

Abiraterone Acetate; durvalumab; Methotrexate; Vinblastine; Doxorubicin; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Matthew Campbell

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: November 30, 2021
• Study Start: October 13, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (2)