- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01499121
Study of Efficacy and Safety of Sunitinib Given on an Individualized Schedule
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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. A more detailed pharmacokinetic blood sampling will be done in a subset of patients in an effort to understand if Sunitinib blood concentration has a tendency to go down during treatment, as has been shown to be the case for Sorafenib. Biomarker and genomics blood sampling for correlation with progression free survival, toxicity and pharmacokinetics will be collected at baseline and stored.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Alberta
-
Calgary, Alberta, Canada, T2N 4N2
- Tom Baker Cancer Centre
-
Edmonton, Alberta, Canada, T6G 1Z2
- Cross Cancer Institute
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V5Z 4E6
- BC Cancer Agency - Vancouver
-
-
Manitoba
-
Winnipeg, Manitoba, Canada, R3E 0V9
- CancerCare Manitoba
-
-
Nova Scotia
-
Halifax, Nova Scotia, Canada, B3H 3A7
- QEII Health Sciences Centre
-
-
Ontario
-
Hamilton, Ontario, Canada, L8V 5C2
- Juravinski Cancer Centre
-
Kingston, Ontario, Canada, K7L 2V7
- Kingston General Hospital Research Institute
-
London, Ontario, Canada, N6A 4L6
- London Health Sciences Centre
-
Oshawa, Ontario, Canada, L1G 2B9
- Durham Regional Cancer Centre
-
Ottawa, Ontario, Canada, K1H 8L6
- Ottawa Hospital Cancer Centre
-
Toronto, Ontario, Canada, M4N 3M5
- Sunnybrook Health Sciences Centre
-
Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Hospital
-
-
Quebec
-
Montreal, Quebec, Canada, H2W 1T8
- Notre-Dame Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed locally recurrent or metastatic renal cell carcinoma of clear cell origin or with a component of clear cell histology.
- Patients with nephrectomy (partial or total) or without nephrectomy are eligible.
- Evidence of measurable disease by RECIST criteria version 1.1.
- Male or female, age ≥ 18 years old
- Karnofsky performance status ≥ 80 %.
- Adequate organ functions determined by protocol directed lab values
- Subject's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion Criteria:
- Renal cell carcinoma without any clear (conventional) cell component.
- Prior systemic therapy of any kind for advanced RCC (including targeted therapy, immunotherapy, chemotherapy, hormonal, or investigational therapy). Prior neo-adjuvant or adjuvant therapy with cytokines, IL-2 or vaccines is only permitted if it did not occur within the preceding 12 months. Prior and/or concurrent bisphosphonate therapy is allowed.
- Major surgery or radiation therapy within 4 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated
- NCI CTCAE Version 3.0 grade 3 haemorrhage within 4 weeks of starting the study treatment
- Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, or in situ cervical cancer
- Known brain metastases, spinal cord compression, or evidence of symptomatic brain or leptomeningeal carcinomatosis on screening CT or MRI scan.
- Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
- Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade ≥2
- Prolonged QTc interval on baseline EKG (>450 msec for males or >470 msec for females).
- Atrial Fibrillation of any grade.
- Uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection.
- Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, and imaging trials are allowed.
- Concomitant treatment with a drug having proarrhythmic potential
- Use of potent CYP3A4 inhibitors and inducers 7 and 12 days before dosing, respectively
- Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum) prior to enrolment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Sunitinib
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival for sunitinib given on an individualized dose/schedule
Time Frame: 3.5 years
|
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.
|
3.5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient tolerability and safety of an individualized dose/schedule
Time Frame: 3.5 years
|
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.
|
3.5 years
|
Dose intensity of sunitinib given on an individualized dose/schedule.
Time Frame: 3.5 years
|
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.
|
3.5 years
|
Overall survival and patient quality of life
Time Frame: 3.5 years
|
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.
|
3.5 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Georg A. Bjarnason, MD, Sunnybrook Health Sciences Centre
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Sunitinib
Other Study ID Numbers
- OZM-042
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Clear Cell, Metastatic Renal Cell Carcinoma
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Renal Cell Carcinoma | Metastatic Clear Cell Renal Cell Carcinoma | Advanced Clear Cell Renal Cell Carcinoma | Stage III Renal Cell Cancer AJCC v8 | Stage IV Renal Cell Cancer AJCC v8 | Metastatic Sarcomatoid Renal Cell Carcinoma | Advanced Renal Cell Carcinoma | Unresectable Renal Cell... and other conditionsUnited States
-
Celldex TherapeuticsTerminatedKidney Neoplasms | Metastatic Renal Cell Carcinoma | Ovarian Clear Cell Carcinoma | Papillary Renal Cell Carcinoma | Renal Cell Carcinoma (RCC) | Clear-cell Renal Cell CarcinomaUnited States
-
Association Pour La Recherche des Thérapeutiques...CompletedClear-cell Metastatic Renal Cell Carcinoma | Clear-cell Renal CarcinomaFrance
-
Millennium Pharmaceuticals, Inc.CompletedClear-cell Metastatic Renal Cell CarcinomaSpain, Czechia, United States, Canada, Italy, United Kingdom, France, Poland
-
Rennes University HospitalCompletedMetastatic Clear Cell Renal Cell CarcinomaFrance
-
Radboud University Medical CenterCompletedMetastatic Clear Cell Renal Cell CarcinomaNetherlands
-
Australian and New Zealand Urogenital and Prostate...Merck Sharp & Dohme LLC; AmgenActive, not recruitingRenal Cell Carcinoma, Clear Cell | Metastatic Kidney CancerAustralia
-
Celldex TherapeuticsTerminatedNeoplasms | Neoplasms by Histologic Type | Kidney Neoplasms | Carcinoma, Renal Cell | Urologic Neoplasms | Urogenital Neoplasms | Kidney Diseases | Urologic Diseases | Clear-cell Metastatic Renal Cell CarcinomaUnited States
-
University of Texas Southwestern Medical CenterTerminatedMetastatic Clear Cell Renal Cell CarcinomaUnited States
-
Abramson Cancer Center of the University of PennsylvaniaUniversity of Pittsburgh; Rutgers Cancer Institute of New JerseyCompletedMetastatic Clear Cell Renal Cell CarcinomaUnited States
Clinical Trials on Sunitinib
-
AGO Study GroupPhilipps University Marburg Medical Center; HSK Reasearch GmbH WiesbadenCompletedPlatinum Refractory Epithelial Ovarian Cancer | Primary Cancer of the Peritoneum | Cancer of the Fallopian TubeGermany
-
Mothaffar RimawiTerminated
-
Cogent Biosciences, Inc.RecruitingMetastatic Cancer | Advanced Gastrointestinal Stromal TumorsUnited States, Korea, Republic of, Spain, United Kingdom, Australia, France, Italy, Netherlands, Taiwan, Germany, Denmark, Hong Kong, Canada, Sweden, Norway, Mexico, Czechia, Argentina, Hungary, Brazil, Chile, Poland
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedKidney CancerUnited States
-
PfizerCompletedBreast NeoplasmsUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
PfizerCompletedGastrointestinal Stromal TumorsKorea, Republic of
-
California Pacific Medical Center Research InstitutePfizer; University of California, San FranciscoCompleted
-
PfizerCompletedGastrointestinal Stromal TumorsUnited States, Czechia, France
-
Asan Medical CenterCompletedMetastatic Renal Cell CarcinomaKorea, Republic of