A single arm, multicenter, phase II trial of everolimus as monotherapy in the palliative treatment of patients with locally advanced or metastatic transitional cell carcinoma after failure of platinum-based chemotherapy.

4542 Background: There is a paucity of chemotherapy options for the treatment of patients who have relapsed following platinum based chemotherapy (CT). Cabazitaxel is a new taxane that showed in-vivo antiproliferative activity on resistant cell lines. Methods: CAB-B1 was a single centre phase II randomised controlled trial of Cabazitaxel (CAB; 25mg/m2 q3 week for 6 cycles) versus best supportive care (BSC) in patients (pts) with histologically proven transitional cell carcinoma (TCC), locally advanced or metastatic, who had received platinum based treatment and recurred within 12 months of the last cycle of CT. Primary outcome was overall response rate (ORR) using RESIST. Secondary outcomes were Progression Free Survival (PFS), Overall Survival (OS), Quality of Life assessment, safety and tolerability. A total of 96 pts required to detect differences in ORR from 5% to 30%; 80% power; 5% alpha level; 10% dropouts. Stopping rules, using Simon’s two stage optimal design to assess the individual effectiveness of CAB, required at least 1 ORR from 10 pts on CAB during 1st stage (i.e. total of 20 pts randomised) and 4 from 29 CAB pts in 2nd stage (assuming lower ORR limit of 0.05, target ORR of 0.20, 80% power, 5% alpha level). The trial was supported by grant from Sanofi. Results: Between January 2013 and October 2016, 20 pts were randomised (10 on each arm). 75% males; median age 68 years; 65% had recurred within 6 months of previous CT. BSC included paclitaxel CT for 9 pts and radiotherapy for 1 pt. 8 pts completed 6 cycles of CT (3 on CAB; 5 on BSC). 6 pts on each arm were evaluated for response after having 2/3 cycles; 2 pts had an ORR on CAB and 1 pt on BSC. 14 pts have died of disease (8 on CAB; 6 on BSC).Median OS was 5.6 months (95% confidence interval (CI) 0.7-15.2) for CAB pts and 8.2 months (95% CI 1.0-8.8) for BSC pts. Median PFS was 4.4 months (95% CI 0.7-9.4) for CAB pts and 4.1 months (95% CI 1.0-6.8) for BSC pts. Conclusions: It has been hard to recruit these poorly patients within a single centre, but CAB-B1 successfully reached the efficacy target for the 1st stage, showing that there could be a role for CAB in these pts. Clinical trial information: NCT01668459.

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Cabazitaxel in Platinum Pre-treated Patients with Locally Advanced or Metastatic Transitional Cell Carcinoma Who Developed Disease Progression after Platinum based Chemotherapy: Results of the Phase II CAB-B1 Trial

International Journal of Cancer Research & Therapy ◽

10.33140/ijcrt.04.04.04 ◽

2019 ◽

Vol 4 (4) ◽

Keyword(s):

Transitional Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Controlled Trial ◽

Locally Advanced ◽

Transitional Cell ◽

Progression Free Survival ◽

Best Supportive Care ◽

Platinum Based Chemotherapy ◽

Randomised Controlled

There is a paucity of chemotherapy options for patients with urothelial cancers who have relapsed following platinum based chemotherapy (CT). CAB-B1 was a single centre phase II randomised controlled trial of Cabazitaxel (CAB; 25mg/m2 q3 week for 6 cycles) versus best supportive care (BSC) in patients with histologically proven transitional cell carcinoma (TCC), locally advanced or metastatic, who had recurred after receiving platinum based treatment. Primary outcome was overall response rate (ORR) using RESIST. Secondary outcomes included Progression Free Survival (PFS) and Overall Survival (OS). Between January 2013 and October 2016, 20 patients were randomised (10 on each arm). BSC included paclitaxel CT for 9 patients and radiotherapy for 1 patient. 8 patients completed 6 cycles of CT (3 on CAB; 5 on BSC). 2 patients had an ORR on CAB and 1 patient on BSC. Median OS was 5.8 months (95% confidence interval (CI) 0.7-14.6) for CAB patients and 7.5 months (95% CI 1.0-10.8) for BSC patients. Median PFS was 4.8 months (95% CI 0.7-8.3) for CAB patients and 3.7 months (95% CI 1.0-7.0) for BSC patients. CAB-B1 successfully reached the efficacy target for 1st stage, showing that there could be a role for CAB in these patients.

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Phase II trial of everolimus monotherapy in the palliative treatment of patients with metastatic transitional cell carcinoma (TCC) after failure of platinum-based therapy: Activity and biomarkers.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.4622 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 4622-4622

Author(s):

E. Seront ◽

B. Sautois ◽

S. Rottey ◽

L. A. D'Hondt ◽

J. Canon ◽

...

Keyword(s):

Transitional Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Palliative Treatment ◽

Phase Ii Trial ◽

Transitional Cell

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Paclitaxel and Gemcitabine Chemotherapy for Advanced Transitional-Cell Carcinoma of the Urothelial Tract: A Phase II Trial of the Minnie Pearl Cancer Research Network

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.12.3018 ◽

2001 ◽

Vol 19 (12) ◽

pp. 3018-3024 ◽

Cited By ~ 138

Author(s):

Anthony A. Meluch ◽

F. Anthony Greco ◽

Howard A. Burris ◽

Timothy O’Rourke ◽

Gregory Ortega ◽

...

Keyword(s):

Transitional Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Objective Response ◽

Transitional Cell ◽

Research Network ◽

Entire Group ◽

Actuarial Survival ◽

Platinum Based Chemotherapy

PURPOSE: To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma of the urothelial tract. PATIENTS AND METHODS: Fifty-four patients with advanced unresectable urothelial carcinoma entered this multi-centered, community-based, phase II trial between May 1997 and December 1999. All patients were treated with paclitaxel 200 mg/m2 by 1-hour intravenous (IV) infusion on day 1 and gemcitabine 1,000 mg/m2 IV on days 1, 8, and 15; courses were repeated every 21 days. Patients who had objective response or stable disease continued treatment for six courses. RESULTS: Twenty-nine of 54 patients (54%; 95% confidence interval, 40% to 67%) had major responses to treatment, including 7% complete responses. With a median follow-up of 24 months, 16 patients (30%) remain alive and nine (17%) are progression-free. The median survival for the entire group was 14.4 months; 1- and 2-year actuarial survival rates were 57% and 25%, respectively. Seven (47%) of 15 patients previously treated with platinum-based chemotherapy responded to paclitaxel/gemcitabine. Grade 3/4 toxicity was primarily hematologic, including leukopenia (46%), thrombocytopenia (13%), and anemia (28%). Ten patients (19%) required hospitalization for neutropenia and fever, and one patient had treatment-related septic death. CONCLUSION: The combination of paclitaxel and gemcitabine is active and well tolerated in the first- or second-line treatment of patients with advanced transitional-cell carcinoma of the urothelial tract. Response rate and duration compare favorably with those produced by other active, first-line regimens. This regimen should be further evaluated in phase II and III studies, as well as in patients with compromised renal function.

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A phase II trial of pemetrexed plus gemcitabine in locally advanced and/or metastatic transitional cell carcinoma of the urothelium

Annals of Oncology ◽

10.1093/annonc/mdl154 ◽

2006 ◽

Vol 17 (10) ◽

pp. 1533-1538 ◽

Cited By ~ 42

Author(s):

H. von der Maase ◽

J. Lehmann ◽

G. Gravis ◽

H. Joensuu ◽

P.F. Geertsen ◽

...

Keyword(s):

Transitional Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Locally Advanced ◽

Transitional Cell

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1326: Phase II Trial of Gemcitabine, Paclitaxel, and Cisplatin in Advanced Transitional Cell Carcinoma

The Journal of Urology ◽

10.1016/s0022-5347(18)35471-5 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 360-360

Author(s):

Peter E. Clark ◽

Diana Stindt ◽

M. Craig Hall ◽

Michele Harmon ◽

James F. Lovato ◽

...

Keyword(s):

Transitional Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Transitional Cell

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Gemcitabine Plus Cisplatin, an Active Regimen in Advanced Urothelial Cancer: A Phase II Trial of the National Cancer Institute of Canada Clinical Trials Group

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.9.2876 ◽

1999 ◽

Vol 17 (9) ◽

pp. 2876-2876 ◽

Cited By ~ 162

Author(s):

Malcolm J. Moore ◽

Eric W. Winquist ◽

Nevin Murray ◽

Ian F. Tannock ◽

Susan Huan ◽

...

Keyword(s):

Transitional Cell Carcinoma ◽

Cell Carcinoma ◽

Urothelial Cancer ◽

Response Rate ◽

Phase Ii Trial ◽

Locally Advanced ◽

Transitional Cell ◽

Grade 3 ◽

Intent To Treat ◽

To Receive

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine (2′,2′-difluorodeoxycytidine) plus cisplatin in previously untreated patients with advanced transitional-cell carcinoma. PATIENTS AND METHODS: Thirty-one patients with measurable advanced transitional-cell carcinoma who had received no prior chemotherapy for metastatic disease were scheduled to receive gemcitabine 1,000 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 and cisplatin 70 mg/m2 over 1 hour on day 2 of a 28-day cycle. Prior adjuvant or neoadjuvant therapy for locally advanced disease was allowed if this was completed more than 1 year before study entry. RESULTS: There were six complete responses and 10 partial responses in 28 assessable patients, for anoverall response rate of 16 of 28 (57%). The response rate on an intent-to-treat basis was 16 of 31 patients (52%). The median survival is 13.2 months, with 18 patients still alive at this time. Toxicity was primarily hematologic, with 12 of 31 patients (39%) having ≥ grade 3 granulocytopenia and 17 of 31 (55%) having ≥ grade 3 thrombocytopenia. Two patients had febrile neutropenia. All patients required a dose modification of gemcitabine at some point in their therapy; the primary reason was thrombocytopenia and/or neutropenia. CONCLUSION: Gemcitabine plus cisplatin is an active regimen for the treatment of urothelial cancer.

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