Study of Efficacy and Safety of Sunitinib Given on an Individualized Schedule
This prospective single arm study will evaluate the efficacy and safety of sunitinib given on an individualized dosing schedule as first-line therapy in subjects with metastatic clear cell renal cell cancer. The treatment schedule intent is to maximize dose intensity of sunitinib and minimize time off therapy based on individual tolerability using protocol directed dose modification criteria. A total of 110 subjects will be enrolled. All subjects will continue to receive study treatment until disease progression or withdrawal of consent. The primary outcome for this study is progression-free survival (PFS), defined as the duration from the date a patient first receives Sunitinib until the date of death or confirmed progression according to the RECIST criteria.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II, Multi-Centre, Study of the Efficacy and Safety of Sunitinib Given on an Individualized Schedule as First-Line Therapy for Metastatic Renal Cell Cancer|
- Progression free survival for sunitinib given on an individualized dose/schedule [ Time Frame: 3.5 years ] [ Designated as safety issue: No ]Primary objective is to characterize the progression free survival for sunitinib given on an individualized dose/schedule in patients on first-line treatment for metastatic renal cell cancer. Subjects will continue therapy until progression according to RECIST criteria version 1.1. Tumour measurements using physical exam, spiral CT scan and/or MRI or other appropriate techniques deemed suitable by the investigator will be performed at screening and repeated at the end of every 2 cycles until disease progression.
- Patient tolerability and safety of an individualized dose/schedule [ Time Frame: 3.5 years ] [ Designated as safety issue: Yes ]To evaluate the tolerability and safety of individualized dose/schedule changes and dose escalation and schedule modification in patients with minimal toxicity after treatment with sunitinib 50 mg for 28 days. The adverse effects of the drug will be assessed from adverse events, vital signs and by clinically significant changes in the lab evaluations and ECG's. Categorical endpoints, will be summarized using proportions and frequencies.
- Dose intensity of sunitinib given on an individualized dose/schedule. [ Time Frame: 3.5 years ] [ Designated as safety issue: No ]The intent is to maximize dose intensity of sunitinib and minimize time off therapy based on individual tolerability using the dose modification criteria outlined in the protocol. Dose and schedule changes are done if toxicity (hematological, fatigue, skin, GI) is > NCI CTCAE (version 3) grade 2. Patients that tolerate the standard 50 mg 28 days on/14 days off schedule with minimal toxicity (grade 1) will be dose escalated in 12.5 mg increments as outlined in the protocol on a schedule of 14 days on and 7 days off to a maximum of 75 mg.
- Overall survival and patient quality of life [ Time Frame: 3.5 years ] [ Designated as safety issue: No ]To characterize the overall survival and study the quality of life in subjects given sunitinib on an individualized dose/schedule. Quality of life questionnaires (ie. FACT-G and FKSI-DRS) will be completed at baseline and every 2 months thereafter until disease progression. Summary scores for QOL outcomes will be reported as the raw value at each time point evaluated, as well as the change in score from baseline. Overall survival will be calculated from the date of registration and estimated using the Kaplan-Meier method.
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Starting dose/schedule of Sunitinib 50 mg/28 days on, 14 days off. The intent is to maximize dose intensity of Sunitinib and minimize time off therapy based on individual tolerability using dose modification criteria.
The starting dose will be 50 mg Sunitinib on the 28/14 schedule. In patients that develop ≥ grade-2 toxicity after 2 weeks, therapy will be held for 7 days or resolution before continuing therapy according to the 1st dose/schedule change. In patients that do not develop ≥ grade-2 toxicity, therapy will continue for 1-2 weeks or until ≥ grade-2 toxicity. In patients that develop > grade-2 toxicity after less than 4 weeks, therapy will be held for 7 days or before continued according to the 1st dose/schedule change. Patients that do develop grade-2 toxicity (but no more) on the 50 mg 28/14 schedule, will remain on schedule but the time off therapy will be reduced to 7 days if toxicity has resolved after a 7-day break. Patients that develop ≤ grade-1 toxicity on the 50 mg 28/14 schedule, will be dose escalated according to protocol.
This is a single-arm, single-stage phase II study investigating the use of an individualized dosing regimen of Sunitinib on patients with metastatic renal cell carcinoma. The intent is to maximize dose intensity of sunitinib and minimize time off therapy based on individual tolerability using protocol directed dose modification criteria. Dose and schedule changes are done if toxicity (hematological, fatigue, skin, GI) is > grade 2. There will be no dosing or schedule changes for hypertension, hypothyroidism, skin color changes, heartburn, etc. unless clinically indicated. Subjects will continue therapy until progression according to RECIST 1.1 criteria. All subjects will be followed for progression free survival until progression but after 2 years on therapy, only grade 3/4 drug related adverse events will be recorded.
Fact-G and FKSI-DRS will be used to evaluate PRO/QOL at baseline and every 2 months timepoints. Pharmacokinetic blood sampling will be collected on cycle 1, day 14 and again on day 14 when a stable sunitinib schedule has been established for each subject. Biomarker and genomics blood sampling for correlation with progression free survival, toxicity and pharmacokinetics will be collected at baseline and stored.
|Contact: Georg A. Bjarnason, MDemail@example.com|
|Contact: Nesan Bandali, RNfirstname.lastname@example.org|
|Tom Baker Cancer Centre||Recruiting|
|Calgary, Alberta, Canada, T2N 4N2|
|Contact: Daniel Heng, MD Daniel.Heng@albertahealthservices.ca|
|Principal Investigator: Daniel Heng, MD|
|Cross Cancer Institute||Recruiting|
|Edmonton, Alberta, Canada, T6G 1Z2|
|Contact: Naveen Basappa, MD (780) 432-8762 Naveen.Basappa@albertahealthservices.ca|
|Principal Investigator: Naveen Basappa, MD|
|Canada, British Columbia|
|BC Cancer Agency - Vancouver||Recruiting|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|Contact: Christian Kollmannsberger, MD (604) 877-6098 email@example.com|
|Principal Investigator: Christian Kollmannsberger, MD|
|Canada, Nova Scotia|
|QEII Health Sciences Centre||Recruiting|
|Halifax, Nova Scotia, Canada, B3H 3A7|
|Contact: Robyn MacFarlane, MD (902) 473-6106 firstname.lastname@example.org|
|Principal Investigator: Robyn MacFarlane, MD|
|Juravinski Cancer Centre||Recruiting|
|Hamilton, Ontario, Canada, L8V 5C2|
|Contact: Sebastien Hotte, MD (905) 387-9495 Sebastien.Hotte@jcc.hhsc.ca|
|Principal Investigator: Sebastien Hotte, MD|
|London Health Sciences Centre||Recruiting|
|London, Ontario, Canada, N6A 4L6|
|Contact: Mary MacKenzie, MD (519) 685-8640 Mary.MacKenzie@lhsc.on.ca|
|Principal Investigator: Mary MacKenzie, MD|
|Durham Regional Cancer Centre||Recruiting|
|Oshawa, Ontario, Canada, L1G 2B9|
|Contact: Pawel Zalewski, MD (905) 576-8711 ext 3625 email@example.com|
|Principal Investigator: Pawel Zalewski, MD|
|Ottawa Hospital Cancer Centre||Recruiting|
|Ottawa, Ontario, Canada, K1H 8L6|
|Contact: Neil Reaume, MD (613) 737-7700 firstname.lastname@example.org|
|Principal Investigator: Neil Reaume, MD|
|Sunnybrook Health Sciences Centre||Recruiting|
|Toronto, Ontario, Canada, M4N 3M5|
|Contact: Georg A. Bjarnason, MD 416-480-5847 email@example.com|
|Contact: Nesan Bandali, RN 416-480-5739 firstname.lastname@example.org|
|Principal Investigator: Georg A. Bjarnason, MD|
|Princess Margaret Hospital||Recruiting|
|Toronto, Ontario, Canada, M5G 2M9|
|Contact: Jennifer Knox, MD (416) 946-2399 Jennifer.Knox@uhn.on.ca|
|Principal Investigator: Jennifer Knox, MD|
|Montreal, Quebec, Canada, H2W 1T8|
|Contact: Denis Soulieres, MD (514) 890-8000 ext 25381 email@example.com|
|Principal Investigator: Denis Soulieres, MD|
|Principal Investigator:||Georg A. Bjarnason, MD||Sunnybrook Health Sciences Centre|