CV301 Combined With PD-1/L1 Blockade in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

Completed · Phase 2

Conditions studied: Bladder Cancer

In brief

This is a Phase 2, single-arm, multi-institutional clinical trial designed to study the combination of CV301 with atezolizumab in the first-line treatment of UC not eligible for cisplatin-containing chemotherapy (Cohort 1) and in the second-line treatment of UC previously treated with standard first-line cisplatin-based chemotherapy (Cohort 2).

Key facts

Study ID

NCT03628716

Run by

Bavarian Nordic

People needed

43

Starts

2018-09-18

Expected to finish

2021-02-02

Last updated by the study team

2022-04-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥ 18 years at date of ICF signature having the ability to comply with protocol.
• Histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV; or metastatic recurrence after locoregional treatment) UC (including renal pelvis, ureters, urinary bladder, urethra)
• Patients with mixed histologies were required to have a dominant transitional cell pattern.
• Locally advanced bladder cancer that was inoperable on the basis of involvement of the pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2-N3).
• Life expectancy ≥ 12 weeks.
• Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions.
• Demonstrate adequate organ function.
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year] when used consistently and correctly) and to continue its use for 5 months after the last dose of atezolizumab.
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or 10-15 unstained slides, with an associated pathology report.
• For Cohort 1:
• Untreated with chemotherapy
• Have at least one of the following:
• ECOG (Eastern Cooperative Oncology Group) performance status of 2.
• Glomerular filtration rate calculated as creatinine clearance (Cockroft-Gault formula) of ≥20 mL/min and less than 60 mL/min
• Hearing loss or neuropathy of any cause Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2
• For Cohort 2:
• Disease progression during or following treatment with at least one platinum-containing regimen (e.g., GC, MVAC, CarboGem, carboplatin-paclitaxel) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence, as defined by:
• Regimen is defined as patients receiving at least one cycle of a platinum-containing regimen with response assessment. Patients who received one cycle of a platinum-containing regimen but discontinued due to toxicity are also eligible.
• Patients who received prior adjuvant/neoadjuvant chemotherapy and progressed within 12 months of treatment with a platinum-containing adjuvant/neoadjuvant regimen are considered as second-line patients.
• ECOG (Eastern Cooperative Oncology Group) performance status of < 2
• Calculated creatinine clearance (Cockroft-Gault formula) of ≥20 mL/min

You may not qualify if…

• Any approved anti-cancer therapy, including chemotherapy, within 3 weeks prior to initiation of trial treatment; the following exceptions are allowed:
• Palliative radiotherapy for bone metastases or non-target soft tissue lesions completed >7 days prior to baseline imaging.
• Hormone-replacement therapy or oral contraceptives.
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to screening given that all AEs related to prior treatment have resolved to baseline or Grade 1.
• Active central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments or Leptomeningeal disease.
• Uncontrolled tumor-related pain:
• Patients requiring pain medication must be on a stable regimen at trial entry.
• Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to trial entry.
• Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) could be considered for loco-regional therapy if appropriate prior to enrollment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• a. Patients with indwelling catheters (e.g., PleurX) are allowed.
• Uncontrolled hypercalcemia (>1.5 mmol/L ionized calcium or Ca >12 mg/dL or corrected serum calcium >ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab:
• Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who did not have a history of clinically significant hypercalcemia are eligible.
• Patients who are receiving denosumab prior to enrollment have to be willing and eligible to receive a bisphosphonate instead while in the trial.
• Malignancies other than urothelial carcinoma within 3 years prior to Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and no intent for further treatment or incidental prostate cancer (T1/T2b, Gleason score ≤7 undergoing active surveillance and treatment naive).
• Pregnant and lactating women.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or aminoglycoside antibiotics or egg products, poxvirus-based vaccinations, or beef or bovine meat.
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation.
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this trial.
• Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this trial.
• Patients with history of vitiligo and controlled psoriasis are eligible for the trial.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Positive test for Human Immunodeficiency Virus (HIV).

Where it is running

• H. Lee Moffitt Cancer Center & Research Institute, Inc. — Tampa, Florida, United States
• Norton Cancer Institute, Norton Healthcare Pavilion — Louisville, Kentucky, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute (DFCI) — Boston, Massachusetts, United States
• University of Utah - Huntsman Cancer Institute — Salt Lake City, Utah, United States
• Seattle Cancer Care Alliance — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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