Clinical trial NCT01481870: Comparison of Sequential Therapies With Sunitinib and Sorafenib in Advanced Renal Cell Carcinoma
Official title: Randomized Comparison of Sequential Therapies With Sunitinib and Sorafenib in Advanced Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Metastatic Renal Cell Carcinoma
Keywords: renal cell carcinoma
sorafenib
sunitinib
crossover
Lead sponsor: Yamagata University
Sponsor class: OTHER
First posted: 2011-11-30
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The clinical benefits of sunitinib and sorafenib have been demonstrated in patients with cytokine-refractory metastatic renal cell carcinoma. Sunitinib has also been shown to improve progression free survival and overall survival in a comparative study with interferon-alpha. When sunitinib is used as first-line molecular-targeted therapy, switching to sorafenib is one of the treatment options after disease progression. Reversely, when sorafenib is used as first-line molecular-targeted therapy, sunitinib is used as second-line therapy. The goal of cancer treatment is cure, and if cure is not possible, it is to prolong survival. In this study, sunitinib or sorafenib will be administered as first-line molecular-targeted therapy and treatment switched to the other test drug, sorafenib or sunitinib, when disease progression is detected to assess which treatment sequence produces longer progression free survival and offers a better safety profile (causing fewer adverse events). The purpose of this trial is to compare progression free survival of first line sunitinib versus sorafenib, and that of two treatment sequences, i.e. sunitinib followed by sorafenib versus sorafenib followed by sunitinib.


Eligibility criteria: Inclusion Criteria:

* Age: 20-80 years old, both inclusive
* ECOG performance status of 0, 1, or 2
* MSKCC risk of favorable or intermediate
* Histologically confirmed renal cell carcinoma
* No ischemic heart disease
* Laboratory findings meet the following criteria:

  1. Respiratory function: %VC, 80% and FEV1.0,70%
  2. Hematology: white blood cell count4,000/mm3, platelet count100,000/mm3
  3. Clinical chemistry: GOT and GPT within the normal range of each medical institution; total bilirubin \<1.5 x ULN
  4. Serum creatinin \<2.0mg/dl, blood urea nitrogen (BUN) \<25mg/dl
  5. Echocardiographic estimation of left ventricular ejection fraction is higher than the lower limit of reference range of each medical institution.

Exclusion Criteria:

* History of any other malignancy
* Central nervous system metastases. However, patients who remain asymptomatic, have no new or enlarging lesion in the CNS within 6 months of enrollment in this study, and require no corticosteroids may be enrolled.
* History of cardiac infarction, unstable angina, congestive heart failure, or symptomatic peripheral vascular disease within 12 months of enrollment
* History of cerebrovascular disorder including transient ischemic attack (TIA)
* Pregnancy or possible pregnancy at any time during the study
* Ongoing grade 2 adverse event prior treatment
* Prior treatment with any anticancer therapy including cytokine therapy such as interferon-alpha and interleukin-2
* Prior treatment with mTOR inhibitor
* Prior treatment with sunitinib or sorafenib
* Treatment with an test drug in a clinical research within 4 weeks of enrollment in this study

Primary outcomes:
measure: Progression free survival in first-line treatment
timeFrame: Time of progression in first line treatment
Secondary outcomes:
measure: Total progression free survival (PFS) in first-line and second-line treatments
timeFrame: Time of progression in second line treatment
Other outcomes:
Locations:
city: Yamagata
country: Japan
facility: Yamagata University Faculty of Medicine
Study officials:
affiliation: Yamagata University Faculty of Medicine
name: Yoshihiko Tomita, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tomita Y, Shinohara N, Yuasa T, Fujimoto H, Niwakawa M, Mugiya S, Miki T, Uemura H, Nonomura N, Takahashi M, Hasegawa Y, Agata N, Houk B, Naito S, Akaza H. Overall survival and updated results from a phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma. Jpn J Clin Oncol. 2010 Dec;40(12):1166-72. doi: 10.1093/jjco/hyq146. Epub 2010 Aug 16.
citation: Tomita Y, Naito S, Sassa N, Takahashi A, Kondo T, Koie T, Obara W, Kobayashi Y, Teishima J, Takahashi M, Matsuyama H, Ueda T, Yamaguchi K, Kishida T, Shiroki R, Saika T, Shinohara N, Oya M, Kanayama HO. Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC. Clin Genitourin Cancer. 2020 Aug;18(4):e374-e385. doi: 10.1016/j.clgc.2020.01.001. Epub 2020 Mar 6.