Sequential Study to Treat Renal Cell Carcinoma

NCT00732914 | Completed Phase 3

• 2 other identifiers: 09072008-13772EudraCT 2008-005011-18
• Study Type: interventional
• Target: 272
• Locations: 1 country
• Sites: 1

Brief 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. 1.Time from first treatment to progression during second-line therapy (total TTP)
2. 2.Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm
3. 3.PFS in first-line and second-line treatment, descriptively
4. 4.Overall survival, descriptively (data cut-off same as for primary endpoint)
5. 5.Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria)
6. 6.Cardiotoxicity analysis by means of echocardiography and NT-pro BNP with an interim analysis after 100 patients of each arm have completed the study
7. 7.Safety and tolerability

Conditions

Renal Cell Carcinoma

Keywords

Renal Cell Carcinoma; Sunitinib; Sorafenib; Sequential

Outcome Measures

Primary Outcomes (1)

• total Progression Free Survival

  Last patient last visit (LPLV) to October 2013

Secondary Outcomes (4)

• Total Time to Progression

  Last patient last visit (LPLV) to October 2013

• Overall survival

  Last patient last visit (LPLV) to October 2013

• Disease Control Rate (DCR)

  Last patient last visit (LPLV) to October 2013

• Cardiotoxicity

  after 100 patients of each arm have completed the study

Study Arms (2)

1

ACTIVE COMPARATOR

Sunitinib (first-line) followed by Sorafenib (second-line)

Drug: Sunitinib (Sutent)

2

EXPERIMENTAL

Sorafenib (first-line) followed by Sunitinib (second-line)

Drug: Sorafenib (Nexavar)

Interventions

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

1

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)

2

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Sponsor GmbH: lead
• iOMEDICO AG: collaborator

Study Sites (1)

Urologische Klinik

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Related Publications (3)

• 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.

  PMID: 37146227 DERIVED

• Eichelberg 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.

  PMID: 25952317 DERIVED

• Calvani 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.

  PMID: 21858552 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Sunitinib; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2008
• First Posted: August 12, 2008
• Study Start: January 1, 2009
• Primary Completion: October 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 23, 2014

Record last verified: 2014-04

Locations

DE (1)