Clinical trial NCT00492258: Sorafenib in Treating Patients at Risk of Relapse After Undergoing Surgery to Remove Kidney Cancer
Official title: SORCE: A Phase III Randomised Double-Blind Study Comparing Sorafenib With Placebo in Patients With Resected Primary Renal Cell Carcinoma at High or Intermediate Risk of Relapse
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Cancer
Keywords: stage II renal cell cancer
stage III renal cell cancer
stage IV renal cell cancer
stage I renal cell cancer
clear cell renal cell carcinoma
papillary renal cell carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-06-27
Enrollment: 1656
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sorafenib after surgery may kill any tumor cells that remain after surgery. It is not yet known whether sorafenib is more effective than a placebo in treating kidney cancer.

PURPOSE: This randomized phase III trial is studying sorafenib to see how well it works compared with a placebo in treating patients at risk of relapse after undergoing surgery to remove kidney cancer.

Detailed description: OBJECTIVES:

* Compare disease-free survival of patients with resected primary renal cell carcinoma at high- or intermediate-risk of relapse treated with a placebo for 3 years vs a placebo for 2 years and sorafenib tosylate for 1 year vs sorafenib tosylate for 3 years.

OUTLINE: This is a randomized, placebo-controlled, double-blind, open-label, multicenter study. Patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive oral placebo twice daily for 3 years in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive oral sorafenib tosylate twice daily for 1 year and oral placebo twice daily for 2 years in the absence of disease progression or unacceptable toxicity.
* Arm III: Patients receive oral sorafenib tosylate twice daily for 3 years in the absence of disease progression or unacceptable toxicity.

Patients in arms I and II with progressive disease may cross over and receive treatment in arm III.

After completion of study treatment, patients are followed periodically.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed renal cell carcinoma (RCC)

  * Clear cell or non-clear cell tumors allowed
  * Intermediate- or high-risk disease (Leibovich score 3 to 11)
* Must have undergone surgery for RCC at least 4 weeks but no more than 3 months prior to study entry

  * No evidence of residual macroscopic disease on post-operative CT scan after resection of RCC

PATIENT CHARACTERISTICS:

* WHO performance status 0-1
* WBC \> 3,400/mm³
* Platelet count \> 99,000/mm³
* Creatinine \< 2.5 times upper limit of normal (ULN)
* Liver function tests \< 1.5 times ULN
* Serum amylase \< 1.5 times ULN
* PT/INR \< 1.5 times ULN
* PTT \< 1.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 9 months after completion of study treatment
* No cardiovascular conditions, including any of the following:

  * Cardiac arrhythmias requiring anti-arrhythmic medication

    * Beta-blockers and digoxin allowed
  * Symptomatic coronary artery disease or ischemia
  * Myocardial infarction within the past 6 months
  * NYHA class II-IV congestive heart failure
* No active clinically serious bacterial or fungal infection
* No known history of HIV infection
* No chronic hepatitis B or C
* No other prior malignancy except carcinoma in situ of the cervix or adequately treated basal cell carcinoma
* No uncontrolled hypertension

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior treatment for RCC other than nephrectomy
* More than 30 days since prior and no other concurrent investigational therapy
* No concurrent medications that have adverse interactions with sorafenib tosylate including, but not limited to, any of the following:

  * Rifampin
  * Grapefruit juice
  * Ritonavir
  * Ketoconazole
  * Itraconazole
  * Hypericum perforatum (St John's wort)
* No concurrent bone marrow transplant or stem cell rescue
* No other concurrent drug that targets angiogenesis, especially VEGF or VEGF receptors (e.g., bevacizumab)
* No other concurrent drug that targets Ras-pathway or EGFR
* No other concurrent anticancer therapy (chemotherapy, immunotherapy, signal transduction inhibition, or hormonal therapy)
* Concurrent non-conventional therapies (e.g., herbs or acupuncture) and vitamin or mineral supplements allowed
* Concurrent bisphosphonates for prophylaxis of osteoporosis allowed

Primary outcomes:
measure: Disease-free survival
Secondary outcomes:
measure: Metastasis-free survival
measure: Disease-specific survival time
measure: Overall survival
measure: Cost effectiveness
measure: Toxicity
Other outcomes:
Locations:
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Dorchester
country: United Kingdom
facility: Dorset County Hospital
state: England
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
state: England
city: Grimsby
country: United Kingdom
facility: Diana Princess of Wales Hospital
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital at Hull and East Yorkshire NHS Trust
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Medical Research Council Clinical Trials Unit
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Dorset Cancer Centre
state: England
city: Portsmouth Hants
country: United Kingdom
facility: Portsmouth Oncology Centre at Saint Mary's Hospital
state: England
city: Prescot Merseyside
country: United Kingdom
facility: Whiston Hospital
state: England
city: Reading
country: United Kingdom
facility: Berkshire Cancer Centre at Royal Berkshire Hospital
state: England
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital
state: England
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Slough, Berkshire
country: United Kingdom
facility: Wexham Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Stoke-On-Trent
country: United Kingdom
facility: University Hospital of North Staffordshire
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
Study officials:
affiliation: Cancer Research UK
name: Timothy Eisen
role: PRINCIPAL_INVESTIGATOR
References:
citation: Eisen T, Frangou E, Oza B, Ritchie AWS, Smith B, Kaplan R, Davis ID, Stockler MR, Albiges L, Escudier B, Larkin J, Bex A, Joniau S, Hancock B, Hermann GG, Bellmunt J, Hodgkinson E, Stewart GD, Barber J, Brown J, McMenemin R, Nathan P, Pickering LM, Parmar MKB, Meade A. Adjuvant Sorafenib for Renal Cell Carcinoma at Intermediate or High Risk of Relapse: Results From the SORCE Randomized Phase III Intergroup Trial. J Clin Oncol. 2020 Dec 1;38(34):4064-4075. doi: 10.1200/JCO.20.01800. Epub 2020 Oct 14.
citation: Blinman PL, Davis ID, Martin A, Troon S, Sengupta S, Hovey E, Coskinas X, Kaplan R, Ritchie A, Meade A, Eisen T, Stockler MR. Patients' preferences for adjuvant sorafenib after resection of renal cell carcinoma in the SORCE trial: what makes it worthwhile? Ann Oncol. 2018 Feb 1;29(2):370-376. doi: 10.1093/annonc/mdx715.
citation: Fairfax BP, Pratap S, Roberts IS, Collier J, Kaplan R, Meade AM, Ritchie AW, Eisen T, Macaulay VM, Protheroe A. Fatal case of sorafenib-associated idiosyncratic hepatotoxicity in the adjuvant treatment of a patient with renal cell carcinoma. BMC Cancer. 2012 Dec 11;12:590. doi: 10.1186/1471-2407-12-590.