Renal Cell CarcinomaPhase 3NCT00732914
Sequential Study to Treat Renal Cell Carcinoma
A Phase 3 study testing Sunitinib (Sutent) and Sorafenib (Nexavar) in people with Renal Cell Carcinoma, run by Sponsor GmbH at 1 site in Germany.
Trial summary
Primary: To evaluate if progression-free survival from first treatment to progression or death during second-line therapy (total PFS) of sorafenib followed by sunitinib is superior compared to sunitinib followed by sorafenib. Secondary: 1. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Sunitinib (Sutent) and Sorafenib (Nexavar)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 272 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2009to Dec 2013
- Phase
- Phase 3
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with metastatic / advanced RCC (all histologies), who are not suitable for cytokine therapy and for whom study medication constitutes first-line therapy
- Age >= 18 ans <= 85years
- ECOG Performance Status of 0 or 1
- MSKCC prognostic score, low or intermediate
- Life expectancy of at least 12 weeks.
- Subjects with at least one uni-dimensional (for RECIST) measurable lesion. Lesions must be measured by CT/MRI-scan.
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- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy:
- Hemoglobin >= 9.0 g/dl
- Absolute neutrophil count (ANC) >= 1,500/mm³
- Platelet count >= 100,000/μl
- Total bilirubin <= 1.5 times the upper limit of normal
- ALT and AST <= 2.5 x upper limit of normal (<= 5 x upper limit of normal for patients with liver involvement of their cancer)
- Alkaline phosphatase < 4 x upper limit of normal
- PT-INR/PT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
- Serum creatinine <= 2 x upper limit of normal.
- Written Informed Consent
Who cannot join
- History of cardiac disease: congestive heart failure >NYHA class 2 or with LVEF at baseline echocardiography < 50%; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension (defined as blood pressure >= 160 mmHg systolic and/or >= 90 mmHG diastolic on medication).
- History of HIV infection or chronic hepatitis B or C
- Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
- Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
- History of organ allograft
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- Patients with evidence or history of bleeding diathesis
- untreated hypothyrosis
- Patients undergoing renal dialysis
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis \& T1] or any cancer curatively treated > 3 years prior to study entry.
- Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 3 months after the completion of trial.
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
- Patients unable to swallow oral medications
- Known allergy to sunitinib or sorafenib or one of its constituents
- Excluded therapies and medications, previous and concomitant:
- Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.
- Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 4 weeks of start of study
- Autologous bone marrow transplant or stem cell rescue within 4 months of study
- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry.
- [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
- Prior exposure to the study drug.
- Any St. John's wort containing remedy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III Randomized Sequential Open-Label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Sunitinib Versus Sunitinib Followed by Sorafenib in the Treatment of First-Line Advanced / Metastatic Renal Cell Carcinoma
Primary:
To evaluate if progression-free survival from first treatment to progression or death during second-line therapy (total PFS) of sorafenib followed by sunitinib is superior compared to sunitinib followed by sorafenib.
Read more
Secondary:
- Time from first treatment to progression during second-line therapy (total TTP)
- Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm
- PFS in first-line and second-line treatment, descriptively
- Overall survival, descriptively (data cut-off same as for primary endpoint)
- Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria)
- Cardiotoxicity analysis by means of echocardiography and NT-pro BNP with an interim analysis after 100 patients of each arm have completed the study
- Safety and tolerability
Read the detailed description
The results of three sequential retrospective studies (Sablin et al, ASCO 2007; Dham et al, ASCO 2007; and Tamaskar et al, 2008) support the sequential administration of sorafenib and sunitinib even though these two drugs have an overlap of targets. These results suggest the lack of cross resistance between sorafenib and sunitinib. This study is a sequential, randomized, open-label (1:1), multicenter phase III study starting in first-line of metastatic / advanced RCC using in the experimental arm sorafenib until progression followed by sunitinib and in the control arm sunitinib until progression followed by sorafenib. Sorafenib-patients will switch to sunitinib and vice versa, with a treatment-free period of at least one and up to maximum four weeks after confirmed first-line treatment failure, in order to avoid additive toxicity. In general, the first-line treatment should be continued until progression (RECIST). However, if patients do not tolerate the first-line medication (sorafenib or sunitinib) because of toxicity, they may cross-over to the second-line therapy (sunitinib or sorafenib) despite the lack of progression, if an appropriate attempt according to a specific dose reduction / interruption scheme has been made to cope with the toxicity and try to resume first line therapy, if deemed appropriate with a reduced dose. In case of discontinuation of first-line treatment because of toxicity, patients will be enrolled for the second-line treatment, only after nonhematological toxicity has resolved to grade ≤1 and hematological toxicity to grade ≤2. As an exception, patients who refuse to be treated further with the first-line regimen due to intolerability despite having no progression may be crossed over to the second-line treatment, if they consent and are in general compliance. Any crossover, also without progression, requires a CT scan, which is in this case also considered the baseline scan for the second-line treatment. One cycle is of six weeks duration. Patients will undergo a CT/MRI scan after every second cycle (i.e. after 12 weeks each), which will be evaluated according to RECIST criteria. There will be no continuation of the same study medication beyond progression in both first- or second-line therapy. After the study reached its primary endpoint cut off, i.e. after 194 endpoint events have occurred, clean data for these patients exist and a statistical analysis has been performed data collection will be stopped. After that the trial is terminated and a close out visit will be performed. Remaining patients will be treated outside the study and will be censored in the analysis.
- Conditions
- Renal Cell Carcinoma
- Being tested
- Sunitinib (Sutent), Sorafenib (Nexavar)
- Keywords
- Renal Cell Carcinoma, Sunitinib, Sorafenib, Sequential
- 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.
Sunitinib (Sutent)Drug
Sunitinib 50 mg once daily 4 weeks on, 2 weeks off, and after discontinuation (due to PD or toxicity), followed by sorafenib 400 mg BID
Sorafenib (Nexavar)Drug
Sorafenib 400 mg BID, followed by Sunitinib 50 mg once daily 4 weeks on, 2 weeks off, and after discontinuation (due to PD or toxicity)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Sunitinib (first-line) followed by Sorafenib (second-line) Receives: Drug: Sunitinib (Sutent) |
| 2 | Experimental | Sorafenib (first-line) followed by Sunitinib (second-line) Receives: Drug: Sorafenib (Nexavar) |
What is being measured
The primary outcome is the main question the study is designed to answer.
total Progression Free Survival
Measured: Last patient last visit (LPLV) to October 2013
Secondary outcomes (4)
Total Time to Progression
Measured: Last patient last visit (LPLV) to October 2013
Overall survival
Measured: Last patient last visit (LPLV) to October 2013
Disease Control Rate (DCR)
Measured: Last patient last visit (LPLV) to October 2013
Cardiotoxicity
Measured: after 100 patients of each arm have completed the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2008 (estimated)
- Study startJan 2009
- Primary completionOct 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 272 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sponsor GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- iOMEDICO AG
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00732914
- Sponsor's protocol ID
- 09072008-13772
- Other IDs
- EudraCT 2008-005011-18
- Status last verified
- Apr 2014
- First submitted
- 11 Aug 2008
- Last updated
- 23 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.
PubMed 37146227Eichelberg C, Vervenne WL, De Santis M, Fischer von Weikersthal L, Goebell PJ, Lerchenmuller C, Zimmermann U, Bos MM, Freier W, Schirrmacher-Memmel S, Staehler M, Pahernik S, Los M, Schenck M, Florcken A, van Arkel C, Hauswald K, Indorf M, Gottstein D, Michel MS. SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer. Eur Urol. 2015 Nov;68(5):837-47. doi: 10.1016/j.eururo.2015.04.017. Epub 2015 May 4.
PubMed 25952317Calvani N, Morelli F, Leo S, Orlando L, Lombardi L, Gnoni A, Cinefra M, Maiello E, Lorusso V, Cinieri S. Sequential use of sorafenib and sunitinib in advanced renal cell carcinoma: does the order of sequencing matter? Med Oncol. 2012 Sep;29(3):1908-13. doi: 10.1007/s12032-011-0048-0. Epub 2011 Aug 20.
PubMed 21858552
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Sequential Open-Label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Sunitinib Versus Sunitinib Followed by Sorafenib in the Treatment of First-Line Advanced / Metastatic Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT00732914
- Acronym / sponsor ID
- 09072008-13772
- Conditions
- Renal Cell Carcinoma
- Keywords
- Renal Cell Carcinoma, Sunitinib, Sorafenib, Sequential
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 272 participants (actual)
- Lead sponsor
- Sponsor GmbHUniversity, hospital or other
- Collaborators
- iOMEDICO AG
- Study start
- Jan 2009
- Primary completion
- Oct 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 12 Aug 2008 (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.
Primary:
To evaluate if progression-free survival from first treatment to progression or death during second-line therapy (total PFS) of sorafenib followed by sunitinib is superior compared to sunitinib followed by sorafenib.
Secondary:
- Time from first treatment to progression during second-line therapy (total TTP)
- Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm
- PFS in first-line and second-line treatment, descriptively
- Overall survival, descriptively (data cut-off same as for primary endpoint)
- Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria)
- Cardiotoxicity analysis by means of echocardiography and NT-pro BNP with an interim analysis after 100 patients of each arm have completed the study
- Safety and tolerability
Detailed description
The results of three sequential retrospective studies (Sablin et al, ASCO 2007; Dham et al, ASCO 2007; and Tamaskar et al, 2008) support the sequential administration of sorafenib and sunitinib even though these two drugs have an overlap of targets. These results suggest the lack of cross resistance between sorafenib and sunitinib. This study is a sequential, randomized, open-label (1:1), multicenter phase III study starting in first-line of metastatic / advanced RCC using in the experimental arm sorafenib until progression followed by sunitinib and in the control arm sunitinib until progression followed by sorafenib. Sorafenib-patients will switch to sunitinib and vice versa, with a treatment-free period of at least one and up to maximum four weeks after confirmed first-line treatment failure, in order to avoid additive toxicity. In general, the first-line treatment should be continued until progression (RECIST). However, if patients do not tolerate the first-line medication (sorafenib or sunitinib) because of toxicity, they may cross-over to the second-line therapy (sunitinib or sorafenib) despite the lack of progression, if an appropriate attempt according to a specific dose reduction / interruption scheme has been made to cope with the toxicity and try to resume first line therapy, if deemed appropriate with a reduced dose. In case of discontinuation of first-line treatment because of toxicity, patients will be enrolled for the second-line treatment, only after nonhematological toxicity has resolved to grade ≤1 and hematological toxicity to grade ≤2. As an exception, patients who refuse to be treated further with the first-line regimen due to intolerability despite having no progression may be crossed over to the second-line treatment, if they consent and are in general compliance. Any crossover, also without progression, requires a CT scan, which is in this case also considered the baseline scan for the second-line treatment. One cycle is of six weeks duration. Patients will undergo a CT/MRI scan after every second cycle (i.e. after 12 weeks each), which will be evaluated according to RECIST criteria. There will be no continuation of the same study medication beyond progression in both first- or second-line therapy. After the study reached its primary endpoint cut off, i.e. after 194 endpoint events have occurred, clean data for these patients exist and a statistical analysis has been performed data collection will be stopped. After that the trial is terminated and a close out visit will be performed. Remaining patients will be treated outside the study and will be censored in the analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Sunitinib (Sutent)Sunitinib (first-line) followed by Sorafenib (second-line) |
| 2 | Experimental | Drug: Sorafenib (Nexavar)Sorafenib (first-line) followed by Sunitinib (second-line) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients with metastatic / advanced RCC (all histologies), who are not suitable for cytokine therapy and for whom study medication constitutes first-line therapy
- Age >= 18 ans <= 85years
- ECOG Performance Status of 0 or 1
- MSKCC prognostic score, low or intermediate
- Life expectancy of at least 12 weeks.
Key exclusion criteria (24 listed)
- History of cardiac disease: congestive heart failure >NYHA class 2 or with LVEF at baseline echocardiography < 50%; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension (defined as blood pressure >= 160 mmHg systolic and/or >= 90 mmHG diastolic on medication).
- History of HIV infection or chronic hepatitis B or C
- Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
- Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
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 (Sutent)Sunitinib 50 mg once daily 4 weeks on, 2 weeks off, and after discontinuation (due to PD or toxicity), followed by sorafenib 400 mg BID | Drug | 1 |
| Sorafenib (Nexavar)Sorafenib 400 mg BID, followed by Sunitinib 50 mg once daily 4 weeks on, 2 weeks off, and after discontinuation (due to PD or toxicity) | Drug | 2 |
Primary outcome
total Progression Free Survival
Time frame: Last patient last visit (LPLV) to October 2013
4 secondary outcomes
Total Time to Progression
Time frame: Last patient last visit (LPLV) to October 2013
Overall survival
Time frame: Last patient last visit (LPLV) to October 2013
Disease Control Rate (DCR)
Time frame: Last patient last visit (LPLV) to October 2013
Cardiotoxicity
Time frame: after 100 patients of each arm have completed the study
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 23 Apr 2014.
- Derived from this study: PubMed 37146227Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.
- Derived from this study: PubMed 25952317Eichelberg C, Vervenne WL, De Santis M, Fischer von Weikersthal L, Goebell PJ, Lerchenmuller C, Zimmermann U, Bos MM, Freier W, Schirrmacher-Memmel S, Staehler M, Pahernik S, Los M, Schenck M, Florcken A, van Arkel C, Hauswald K, Indorf M, Gottstein D, Michel MS. SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer. Eur Urol. 2015 Nov;68(5):837-47. doi: 10.1016/j.eururo.2015.04.017. Epub 2015 May 4.
- Derived from this study: PubMed 21858552Calvani N, Morelli F, Leo S, Orlando L, Lombardi L, Gnoni A, Cinefra M, Maiello E, Lorusso V, Cinieri S. Sequential use of sorafenib and sunitinib in advanced renal cell carcinoma: does the order of sequencing matter? Med Oncol. 2012 Sep;29(3):1908-13. doi: 10.1007/s12032-011-0048-0. Epub 2011 Aug 20.
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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 3 study testing Sunitinib (Sutent) and Sorafenib (Nexavar) in people with Renal Cell Carcinoma, run by Sponsor GmbH at 1 site in Germany.
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 24 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 23 Apr 2014. 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 Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
total Progression Free Survival (time frame: Last patient last visit (LPLV) to October 2013). 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 NCT00732914, which also lists 3 linked publications.
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 23 Apr 2014.