Metastatic Renal Cell CarcinomaPhase 2NCT02071641
Phase II Study of Sunitinib Rechallenge in Patients With Metastatic Renal Cell Carcinoma
A Phase 2 study testing Sunitinib in people with Metastatic Renal Cell Carcinoma, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
Targeted therapies are associated with (acquired) resistance after a median of 5-11 months of treatment, resulting in disease progression, while almost no tumors are intrinsically resistant in the first line setting. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Renal Cell Carcinoma
- What is being tested?
- Sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2012to Sep 2016
- 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
- Patients with histologically or cytologically confirmed clear-cell mRCC.
- Patients who progressed on first-line treatment with sunitinib and who had clinical benefit defined as a response (according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria) or SD for more than 6 months on this treatment.
- Patients who progressed after second-line treatment (mTOR inhibitor or other treatment as long as patients are not treated with a Vascular Endothelial Growth Factor (VEGF) targeted Tyrosine Kinase Inhibitor (TKI), see exclusion criteria), or who progressed after a treatment-free interval of at least 3 months since discontinuation of first-line sunitinib treatment.
- Patients with radiological (and/or clinical) confirmed progressive disease according to RECIST 1.1 criteria.
- Measurable or evaluable disease as defined by RECIST 1.1.
- WHO performance status 0-2.
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- Life expectancy of at least 12 weeks.
- Age 18 years or older.
- Able to receive oral medication.
- Able to provide written informed consent.
- Adequate hematologic function: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hb ≥ 6.0 mmol/L.
- Patients with brain metastases are eligible if they have been stable for at least two months post-radiation therapy or surgery.
- No other current malignant disease, except for basal cell carcinoma of the skin.
- Adequate hepatic function: serum bilirubin ≤ 1.5 x Upper Limit of Normal (ULN), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 x ULN (or ≤ 5 times ULN if liver metastases are present).
- Renal function: estimated glomerular filtration rate ≥ 40 ml/min.
- Patients with reproductive potential must use effective contraception. Female patients must have a negative pregnancy test.
Who cannot join
- Patients treated with any VEGF targeted TKI (sorafenib, pazopanib, axitinib, dovitinib) as second-line treatment after progression on first-line sunitinib treatment.
- Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements on at least 2 separate days.
- Active infection or serious intercurrent illness.
- Presence of unstable angina, recent myocardial infarction (within the previous 3 months).
- Macroscopic hematuria.
- Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance.
- Any other major illness that, in the investigator's judgment, substantially increases the risk associated with the subject's participation in the study.-
Trial locations and contacts
1 site in 1 country.
About this study
Targeted therapies are associated with (acquired) resistance after a median of 5-11 months of treatment, resulting in disease progression, while almost no tumors are intrinsically resistant in the first line setting. The investigators recently published that tumor cell resistance to sunitinib may be directly related to lysosomal sequestration of sunitinib. This resistance mechanism was shown to be transient, since a drug-free culture period could normalize the lysosomal storage capacity for sunitinib and resulted in recovery of drug sensitivity.
In two reports it has been suggested that patients with metastatic Renal Cell Carcinoma who responded to sunitinib in the first-line setting may benefit from rechallenge with sunitinib after failure of second-line treatment. However, these data are retrospective. A prospective trial to investigate a rechallenge with sunitinib is needed to determine whether this strategy is of benefit for patients with mRCC with prior clinical benefit to sunitinib but who stopped treatment because of overt clinical resistance.
- Conditions
- Metastatic Renal Cell Carcinoma
- Being tested
- Sunitinib
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib | Experimental | Patients will be treated in repeated 6-week cycles with 50 mg sunitinib orally daily for 4 weeks followed by 2 weeks off. Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
To investigate the proportion of patients with metastic Renal Cell Carcinoma retreated with sunitinib that is progression-free at 3 months.
Measured: After 3 months of treatment
Secondary outcomes (6)
Clinical benefit rate
To assess the clinical benefit rate (ORR and SD), median Progression Free Survival (mPFS) and Overall Survival (OS) in individuals retreated with sunitinib.
Measured: progression free at 3 months
Effects of sunitinib rechallenge on LAMP1/2 proteins
To assess the effects of sunitinib rechallenge on Lysosome-associated membrane protein 1/2(LAMP1/2) proteins in Peripheral Blood Mononuclear Cells and tumor tissue.
Measured: Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death)
The immunological effects of sunitinib rechallenge
To assess the immunological effects of sunitinib rechallenge on the number and activation state of circulating Dendritic Cell(DC), Myeloid-Derived Suppressor cell (MDSC) and Regulatory T-cell (Tregs).
Measured: Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death).
Mass spectrometry-based identification of phosphorylated proteins in tumor tissue during treatment
To study phosphoproteomic profiles of tumors before rechallenge and at the time of progression. LC-MS/MS-based phospho-proteomics for the identification of sunitinib response and resistance biomarkers
Measured: Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death).
Concentrations of sunitinib
To assess sunitinib drug levels and tumor tissue concentrations of sunitinib.
Measured: Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death).
Effect of retreatment
To evaluate the effect of retreatment with sunitinib on the quality of life.
Measured: progression free at 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2014 (estimated)
- Study startOct 2012
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, H.M.W. Verheul, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02071641
- Sponsor's protocol ID
- 2012/259
- Status last verified
- Apr 2017
- First submitted
- 27 Sep 2013
- Last updated
- 7 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Sunitinib Rechallenge in Patients With Metastatic Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02071641
- Acronym / sponsor ID
- 2012/259
- Conditions
- Metastatic Renal Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 26 Feb 2014 (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.
Targeted therapies are associated with (acquired) resistance after a median of 5-11 months of treatment, resulting in disease progression, while almost no tumors are intrinsically resistant in the first line setting. The investigators recently published that tumor cell resistance to sunitinib may be directly related to lysosomal sequestration of sunitinib. This resistance mechanism was shown to be transient, since a drug-free culture period could normalize the lysosomal storage capacity for sunitinib and resulted in recovery of drug sensitivity.
In two reports it has been suggested that patients with metastatic Renal Cell Carcinoma who responded to sunitinib in the first-line setting may benefit from rechallenge with sunitinib after failure of second-line treatment. However, these data are retrospective. A prospective trial to investigate a rechallenge with sunitinib is needed to determine whether this strategy is of benefit for patients with mRCC with prior clinical benefit to sunitinib but who stopped treatment because of overt clinical resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | Experimental | Drug: SunitinibPatients will be treated in repeated 6-week cycles with 50 mg sunitinib orally daily for 4 weeks followed by 2 weeks off. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients with histologically or cytologically confirmed clear-cell mRCC.
- Patients who progressed on first-line treatment with sunitinib and who had clinical benefit defined as a response (according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria) or SD for more than 6 months on this treatment.
- Patients who progressed after second-line treatment (mTOR inhibitor or other treatment as long as patients are not treated with a Vascular Endothelial Growth Factor (VEGF) targeted Tyrosine Kinase Inhibitor (TKI), see exclusion criteria), or who progressed after a treatment-free interval of at least 3 months since discontinuation of first-line sunitinib treatment.
- Patients with radiological (and/or clinical) confirmed progressive disease according to RECIST 1.1 criteria.
- Measurable or evaluable disease as defined by RECIST 1.1.
Key exclusion criteria (7 listed)
- Patients treated with any VEGF targeted TKI (sorafenib, pazopanib, axitinib, dovitinib) as second-line treatment after progression on first-line sunitinib treatment.
- Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements on at least 2 separate days.
- Active infection or serious intercurrent illness.
- Presence of unstable angina, recent myocardial infarction (within the previous 3 months).
- Macroscopic hematuria.
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 |
|---|---|---|
| Sunitinib | Drug | Sunitinib |
Primary outcome
Progression free survival
Time frame: After 3 months of treatment
To investigate the proportion of patients with metastic Renal Cell Carcinoma retreated with sunitinib that is progression-free at 3 months.
6 secondary outcomes
Clinical benefit rate
Time frame: progression free at 3 months
Effects of sunitinib rechallenge on LAMP1/2 proteins
Time frame: Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death)
The immunological effects of sunitinib rechallenge
Time frame: Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death).
Mass spectrometry-based identification of phosphorylated proteins in tumor tissue during treatment
Time frame: Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death).
Concentrations of sunitinib
Time frame: Blood samples will be collected at baseline, t=4 wk, t=6 wk, t=12 wk and at the end of study treatment (disease progression and/or death).
Effect of retreatment
Time frame: progression free at 3 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2017.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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 Metastatic Renal Cell Carcinoma, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 16 inclusion and 7 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: stopped early, as of the sponsor's last update on 7 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 was stopped early. Results are not available in the source record.
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 (time frame: After 3 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Apr 2017.