Single arm phase I/II study of everolimus and intravesical gemcitabine in patients with primary or secondary carcinoma in situ of the bladder who failed bacillus Calmette Guerin (NCT01259063) Journal Article
| Authors: | Dalbagni, G.; Benfante, N.; Sjoberg, D. D.; Bochner, B. H.; Donat, S. M.; Herr, H. W.; McCoy, A. S.; Fahrner, A. J.; Retinger, C.; Rosenberg, J. E.; Bajorin, D. F. |
| Article Title: | Single arm phase I/II study of everolimus and intravesical gemcitabine in patients with primary or secondary carcinoma in situ of the bladder who failed bacillus Calmette Guerin (NCT01259063) |
| Abstract: | Background: Standard treatment for BCG-refractory urothelial cancer is radical cystectomy. Identification of active agents is clearly warranted. Objective: To determine a safe dose of oral everolimus in combination with standard intravesical gemcitabine and to evaluate the efficacy of this combination. Methods: Patients with carcinoma in situ refractory to intravesical bacillus Calmette-Guérin and refusing cystectomy were eligible. Patients in the phase I part of the trial received one of three dose levels of oral everolimus. Patients also received a fixed dose of intravesical gemcitabine. Maintenance everolimus was given for 12 months in patients achieving a complete response confirmed by cystoscopy and cytology. Patients in phase II received continuous everolimus administered at 10 mg daily with intravesical gemcitabine followed by everolimus maintenance for 12 months of total therapy. The enrollment goal for the phase II was 33 patients. Results: 14 patients were enrolled in phase I of the trial. 23 patients were enrolled in phase II of the trial and 19 were evaluable for primary and secondary endpoints. Four patients withdrew consent prior to treatment initiation. Of the 19 patients evaluable for response, 3 (16%, 95% confidence interval [CI] 3%–40%) were disease free at 1 yr. The probability of RFS was 20% (95% CI 5%–42%) at 12 months. Ten patients out of 19 had grade 3 or greater toxicity events. Seven withdrew consent or were taken off study. Conclusions: Many patients withdrew, and enrollment was halted. Continuous oral everolimus plus intravesical gemcitabine was not well tolerated in this patient population where the threshold for tolerability is low. © 2017 – IOS Press and the authors. All rights reserved. |
| Keywords: | adult; clinical article; aged; primary tumor; drug tolerability; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; drug withdrawal; patient selection; gemcitabine; bcg vaccine; metastasis; infection; multiple cycle treatment; phase 2 clinical trial; maintenance therapy; continuous infusion; bladder cancer; abdominal pain; carcinoma in situ; drug response; disease free interval; skin disease; phase 1 clinical trial; bladder carcinoma; drug treatment failure; neurologic disease; phase ii; gastrointestinal disease; urothelial cancer; metabolic disorder; everolimus; musculoskeletal disease; endocrine disease; hematologic disease; vascular disease; respiratory tract disease; recurrence free survival; mtor inhibitor; rad001; urinary tract disease; intravesical chemotherapy; human; male; female; priority journal; article |
| Journal Title: | Bladder Cancer |
| Volume: | 3 |
| Issue: | 2 |
| ISSN: | 2352-3727 |
| Publisher: | IOS Press |
| Date Published: | 2017-01-01 |
| Start Page: | 113 |
| End Page: | 119 |
| Language: | English |
| DOI: | 10.3233/blc-170095 |
| PROVIDER: | scopus |
| PMCID: | PMC5409047 |
| PUBMED: | 28516156 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 September 2018 -- Source: Scopus |
