A study to asses safety and effectiveness of Nivolumab in combination with the study drug (IPI-549) compared to Nivolumab as single therapy to treat patients with advanced urothelial cancer.
- Conditions
- Advanced Urothelial CarcinomaMedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000854-69-CZ
- Lead Sponsor
- Infinity Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
1.=18 years of age.
2.Have signed and dated an independent review board (IRB)/independent ethics committee (IEC) approved informed consent form (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
3.Willing and able to comply with scheduled visits, treatment schedule, laboratory tests, fresh tumor biopsies, and all other protocol requirements.
4.Patients with histologically or cytologically confirmed urothelial carcinoma (including mixed histologies of urothelial carcinoma with elements of other subtypes) of the renal pelvis, ureter, bladder, or urethra, who meet one of the following:
a.Have progression or refractory disease. Patients must have had at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
b.Have disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy; or
5.At least 1 measurable disease lesion by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by RECIST v1.1 performed within 1 month prior to first dose.
6.Willing to undergo one pre-treatment core biopsy (unless archival tumor tissue is available within 3 months of first dose) and one on-treatment tumor biopsy with an additional (optional) post-treatment tumor biopsy for an exploratory analysis of mechanisms of resistance. Biopsies performed during the study may be omitted under certain circumstances; for example, if considered medically unfeasible after a discussion between the Investigator and Medical Monitor.
Baseline tumor biopsies should preferably be performed from a tumor site that is NOT the only site of measurable disease. For patients with only one site of measurable disease, tumor biopsies are allowed if at least one of the following criteria is met:
a.CT imaging performed after biopsy and there is still measurable disease, or
b.The type of biopsy is not expected to impact the measurability (eg, core needle biopsy) regardless of when imaging occurred, prior to or after biopsy.
Tumor material from core biopsies done before the screening period is acceptable if the biopsy was performed within 3 months prior to the planned treatment start and no new systemic cancer therapy was administered after the biopsy and before study entry.
7.Tumor tissue (archived [without time constraints] or new biopsy) should be provided for biomarker analysis, including PD-L1 expression level per central laboratory (Dako PD-L1 immunohistochemical 28-8 pharmDx kit).
8.Blood sample must be provided to the central laboratory for evaluation of mMDSC levels, as measured by Clinical Laboratory Improvement Amendments (CLIA)-certified Serametrix flow cytometry assay. Patients must have a confirmed result of mMDSC level for randomization into the study.
9.Eastern Cooperative Oncology Group (ECOG) performance status =1.
10.Baseline laboratory values must meet the following criteria within 14 days of the first dose:
a.Adequate hematologic function, defined as white blood cell (WBC) count =2.0 × 109/L, absolute neutrophil count =1.5 × 109/L, hemoglobin =9.0 g/dL, and platelet count =100 × 109/L.
b.Creatinine clearance =30 mL/min, as determined by either of the following:
?Estimation as calculated by Cockcroft-Gault equation;
?Direct measurement by 24-hour urine collection.
c.Aspartate aminotransferase (AST) and alanine amino
Patients are to be excluded from the study if they meet any of the following criteria:
1.Active brain metastases or leptomeningeal metastases. Patients with brain metastases are eligible if these have been treated and there is no MRI evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration. Patients with incidental findings of asymptomatic brain metastases at screening may start study treatment without prior radiation treatment after discussion between the Infinity Medical Monitor or designee and Investigator.
2.Any serious or uncontrolled medical disorder that, in the opinion of the Investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the patient to receive protocol therapy, or interfere with the interpretation of study results.
3.Other prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been definitively treated with curative intent, does not require ongoing treatment, has no evidence of residual active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the primary and secondary endpoints of the study, including response rate and safety.
4.Active, known, or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
5.Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first dose. Inhaled or topical steroids, and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
6.Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, including ipilimumab, or other medicines specifically targeting the T cell; or IPI-549.
7.Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment (patients with prior cytotoxic or investigational products <28 days prior to treatment might be eligible after discussion between Investigator and Infinity Medical Monitor or designee, if toxicities from the prior treatment have resolved to CTCAE Grade 1 level).
8.Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization.
9.Major surgery within 4 weeks prior to Screening.
10.Positive test for hepatitis B virus (HBV) using hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) or positive test for hepatitis C virus (HCV) using HCV RNA test indicating acute or chronic infection.
11.Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
12.Dependence on continuous supplemental oxygen use.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method