Clear Cell, Metastatic Renal Cell CarcinomaPhase 2NCT01499121
Study of Efficacy and Safety of Sunitinib Given on an Individualized Schedule
A Phase 2 study testing Sunitinib in people with Clear Cell, Metastatic Renal Cell Carcinoma, run by Sunnybrook Health Sciences Centre at 13 sites in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clear Cell, Metastatic Renal Cell Carcinoma
- What is being tested?
- Sunitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 13 sitesCanada
- Study dates
- May 2012to 30 Sep 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Canada13 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
QEII Health Sciences Centre
Halifax, Nova Scotia, B3H 3A7
Juravinski Cancer Centre
Hamilton, Ontario, L8V 5C2
Kingston General Hospital Research Institute
Kingston, Ontario, K7L 2V7
London Health Sciences Centre
London, Ontario, N6A 4L6
Notre-Dame Hospital
Montreal, Quebec, H2W 1T8
Durham Regional Cancer Centre
Oshawa, Ontario, L1G 2B9
Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
BC Cancer Agency - Vancouver
Vancouver, British Columbia, V5Z 4E6
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
About this study
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
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.
Read the 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.
- Being tested
- Sunitinib
- Medical subject headings
- Clear-cell metastatic renal cell carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Sutent, SU11248
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.
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib | Other | 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. Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival for sunitinib given on an individualized dose/schedule
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.
Measured: 3.5 years
Secondary outcomes (3)
Patient tolerability and safety of an individualized dose/schedule
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.
Measured: 3.5 years
Dose intensity of sunitinib given on an individualized dose/schedule.
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.
Measured: 3.5 years
Overall survival and patient quality of life
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.
Measured: 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2011 (estimated)
- Study startMay 2012
- Primary completion30 Sep 2017
- Study completion30 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clear Cell, Metastatic Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Dr. Georg Bjarnason, Sunnybrook Health Sciences Centre
- Investigators
- Georg A. Bjarnason, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01499121
- Sponsor's protocol ID
- OZM-042
- Status last verified
- Mar 2018
- First submitted
- 12 Dec 2011
- Last updated
- 6 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bjarnason GA, Knox JJ, Kollmannsberger CK, Soulieres D, Ernst DS, Zalewski P, Canil CM, Winquist E, Hotte SJ, North SA, Heng DYC, Macfarlane RJ, Venner PM, Kapoor A, Hansen AR, Eigl BJ, Czaykowski P, Boyd B, Wang L, Basappa NS. The efficacy and safety of sunitinib given on an individualised schedule as first-line therapy for metastatic renal cell carcinoma: A phase 2 clinical trial. Eur J Cancer. 2019 Feb;108:69-77. doi: 10.1016/j.ejca.2018.12.006. Epub 2019 Jan 14.
PubMed 30648632
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01499121
- Acronym / sponsor ID
- OZM-042
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- May 2012
- Primary completion
- 30 Sep 2017 (actual)
- Study completion
- 30 Sep 2017 (actual)
- First posted
- 26 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | Other | Drug: SunitinibStarting 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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 %.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SunitinibAlso: Sutent, SU11248The 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. | Drug | Sunitinib |
Primary outcome
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 secondary outcomes
Patient tolerability and safety of an individualized dose/schedule
Time frame: 3.5 years
Dose intensity of sunitinib given on an individualized dose/schedule.
Time frame: 3.5 years
Overall survival and patient quality of life
Time frame: 3.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2018.
- Derived from this study: PubMed 30648632Bjarnason GA, Knox JJ, Kollmannsberger CK, Soulieres D, Ernst DS, Zalewski P, Canil CM, Winquist E, Hotte SJ, North SA, Heng DYC, Macfarlane RJ, Venner PM, Kapoor A, Hansen AR, Eigl BJ, Czaykowski P, Boyd B, Wang L, Basappa NS. The efficacy and safety of sunitinib given on an individualised schedule as first-line therapy for metastatic renal cell carcinoma: A phase 2 clinical trial. Eur J Cancer. 2019 Feb;108:69-77. doi: 10.1016/j.ejca.2018.12.006. Epub 2019 Jan 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Georg A. Bjarnason, MD principal investigator
Sunnybrook Health Sciences Centre
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sunitinib in people with Clear Cell, Metastatic Renal Cell Carcinoma, run by Sunnybrook Health Sciences Centre at 13 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival for sunitinib given on an individualized dose/schedule (time frame: 3.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01499121, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2018.