Neoadjuvant Durvalumab Alone Versus Durvalumab With Olaparib in Patients Ineligible for Cisplatin With Muscle-Invasive Urothelial Carcinoma of the Bladder Followed by Radical Cystectomy

NCT04579133 | Terminated Phase 2

• 1 other identifier: LACOG 0219
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a phase II, randomized, open-label, clinical trial including patients with muscle-invasive transitional cell carcinoma of the bladder candidates for radical cystectomy. The study will include patients ineligible for cisplatin. Patients will be centrally randomized in a 1:1 ratio to receive durvalumab plus olaparib (Arm A) or durvalumab alone (Arm B). The clinical study´s hypothesis is that for patients with muscle-invasive transitional cell carcinoma of the bladder who are not fit for cisplatin-based neoadjuvant chemotherapy, Durvalumab monotherapy will have a similar efficacy to historical chemotherapy controls and Durvalumab in combination with olaparib will be associated with an even improved efficacy results in terms of pathologic complete response (pCR).

Conditions

Bladder Cancer; Urothelial Carcinoma

Keywords

Bladder neoplasms; Bladder Cancer; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate (pCR)

  no evidence of invasive residual cancer (ypT0 or Tis/ypN0) in the surgical specimen.

  24 weeks

Secondary Outcomes (5)

• Overall Response rate (RR)

  9 weeks

• Pathological Response including Downstaging to Non-muscle-invasive Cancer in the Surgical Specimen (pPR)

  24 weeks.

• Disease Free Survival (DFS)

  5 years.

• Overall Survival (OS)

  5 years.

• Safety (proportion of adverse events)

  24 weeks

Study Arms (2)

durvalumab plus olaparib

EXPERIMENTAL

Durvalumab 1500 mg IV week 0, 3, 6 plus Olaparib tablets will be given orally on a continuous dosing schedule 300 mg BID OR 200 mg BID (if glomerular filtration rate \[GFR\] 31 to 50 mL/min) to complete 9 weeks of treatment.

Drug: Olaparib; Drug: Durvalumab

durvalumab alone

EXPERIMENTAL

Durvalumab 1500 mg IV week 0, 3, 6 to complete 9 weeks of treatment

Drug: Durvalumab

Interventions

Olaparib DRUG

300 mg BID OR 200 mg BID (if glomerular filtration rate \[GFR\] 31 to 50 mL/min)

durvalumab plus olaparib

Durvalumab DRUG

Durvalumab 1500 mg IV

durvalumab alone; durvalumab plus olaparib

Eligibility Criteria

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

You may qualify if:

• \. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• \. Age \> 18 years at time of study entry. 3. Evidence of muscle-invasive bladder cancer in a pretreatment transurethral biopsy sample.
• \. All histologic subtypes (with exception of small-cell carcinoma) will be eligible if urothelial carcinoma was the predominant histopathologic feature.
• \. Clinical stage T2-T4aN0M0 or T1-T4aN1M0 disease on imaging by American Joint Commission on Cancer, eighth edition.
• \. Available primary tumor tissue (formalin-fixed paraffin embedded FFPE or slides) from transurethral biopsy/resection for biorepository.
• \. Patient must be planning to undergo a radical cystectomy at the time of randomization.
• \. Unfit for cisplatin-based neoadjuvant chemotherapy defined as the presence of at least one of the characteristics below:
• Creatinine clearance less than 60 mL/min;
• Grade 2 or worse hearing loss;
• Grade 2 or worse neuropathy;
• New York Heart Association class III heart failure. 10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 11. Body weight \>30kg 12. Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥10.0 g/dL with no blood transfusion in the past 28 days
• Absolute neutrophil count (ANC) 1.5 x 109/L
• Platelet count ≥100 x 109/L
• Total bilirubin ≤1.5 x institutional upper limit of normal (ULN).

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 3 weeks.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Any concurrent or within 3 weeks prior to study treatment systemic chemotherapy, IP, biologic, hormonal therapy or radiotherapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Patients must have recovered from any effects of any major surgery.
• History of allogenic organ transplantation or double umbilical cord blood transplantation (dUCBT).
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], 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
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• History of another primary malignancy except for

Sponsors & Collaborators

• Latin American Cooperative Oncology Group: lead

Study Sites (1)

Centro de Pesquisa em Oncologia

Porto Alegre, Brazil

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

olaparib; durvalumab

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

Study Design

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

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 8, 2020
• Study Start: March 1, 2021
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: June 16, 2021

Record last verified: 2021-06

Locations

BR (1)