Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With … (NCT04197986) | Clinical Trial Compass
TerminatedPhase 3
Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations
Stopped: The sponsor has decided to close the study due to the discontinuation of infigratinib development. The discontinuation of the study was not due to safety reasons.
United States39 participantsStarted 2020-03-11
Plain-language summary
This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy of infigratinib (an oral targeted FGFR1-3 inhibitor) versus placebo, as adjuvant treatment following surgery in adult subjects with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations (mutations, and gene fusions or rearrangements) who have disease that is considered at high risk for recurrence with surgery alone. The study enrolls subjects with either bladder cancer post radical cystectomy or upper tract urothelial cancer post distal ureterectomy and/or nephrectomy. Study treatment is randomized 1:1 between infigratinib or placebo with treatment up to 1 year or until invasive local, distal, or metastatic disease recurrence confirmed by independent imaging reviewer.
Who can participate
Age range18 Years
SexALL
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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Are randomized within 120 days following nephroureterectomy, distal ureterectomy or cystectomy.
✓. Have histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations. Variant histology is allowed provided urothelial carcinoma is predominant (\>50%). Neuroendocrine (including small and large cell), sarcomatoid, and plasmacytoid variants are excluded (any component).
✓. Regarding samples and documentation of FGFR3
✓. If status post neoadjuvant chemotherapy, pathologic stage at surgical resection must be Stage ≥ ypT2 and/or yN+. Prior neoadjuvant therapy is defined as at least 3 cycles of neoadjuvant cisplatin-based chemotherapy with a planned cisplatin dose of 70 mg/m2/cycle. Subjects who received less than this or non-cisplatin-based neoadjuvant treatment are not excluded.
✓. If not status post neoadjuvant chemotherapy, is ineligible to receive cisplatin-based adjuvant chemotherapy based on Galsky criteria:
✓. Subjects who refuse cisplatin-based chemotherapy or who are ineligible to receive cisplatin-based chemotherapy based on Galsky criteria must also meet the following criteria:
✓. Must have a centrally reviewed negative postoperative computed tomography (CT) (defined as lymph nodes with short axis \<1.0 cm and without growth and no distant metastases according to \[RECIST v1.1 criteria or negative biopsy within 28 days before randomization to confirm absence of disease at baseline.
What they're measuring
1
Centrally Determined Disease-free Survival (DFS)
Timeframe: The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause.
✓. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
Exclusion criteria
✕. Presence of positive invasive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy. In subjects not eligible for further surgery, radiotherapy, or other efficacious treatment, microscopic positive noninvasive margins (eg, carcinoma in situ) without gross residual disease are allowed.
✕. Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days.
✕. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known moderate or strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Prior anticancer or other therapies are restricted as follows:
✕. Prior adjuvant treatment for urothelial cancer is not allowed.
✕. Prior neoadjuvant therapy (eg, chemotherapy, immunotherapy, or investigational) is allowed if inclusion criterion #4 is met. Prior neoadjuvant chemotherapy must have been completed within a period of time that is greater than the cycle length used for that treatment before first dose of study drug.
✕. Prior biologic, immunotherapy, or investigational therapy should have been completed within a period that is ≥5 half-lives or 30 days, whichever is shorter, before the first dose of study drug.
✕. Have previously or currently is receiving treatment with a mitogen-activated protein kinase (MEK) or selective FGFR inhibitor.
✕. Have a history of primary malignancy within the past 3 years other than (1) invasive UBC or UTUC (ie, disease under study), (2) noninvasive urothelial carcinoma, (3) any adequately treated in situ carcinoma or non-melanoma carcinoma of the skin, (4) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (5) an untreated cancer on active surveillance that may not affect the subject's survival status for ≥3 years based on clinician assessment/statement and with medical monitor approval.