Clinical trial NCT01599754: Adjuvant Axitinib Therapy of Renal Cell Cancer in High Risk Patients
Official title: Adjuvant Axitinib Treatment of Renal Cancer: A Randomized Double-blind Phase 3 Study of Adjuvant Axitinib vs. Placebo in Subjects at High Risk of Recurrent RCC
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Clear Cell Renal Carcinoma
Keywords: renal cell carcinoma
axitinib
tyrosine kinase inhibitor
Lead sponsor: SFJ Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
name: SFJ Pharmaceuticals, Inc.
First posted: 2012-05-16
Enrollment: 724
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this trial is to determine if adjuvant therapy with axitinib will prevent or delay the recurrence of renal cell cancer after surgery to remove the primary tumor in high risk patients.

Detailed description: This is a prospective, randomized, double blind placebo controlled Phase 3 trial of oral axitinib starting at 5 mg twice daily given 3 years vs. placebo.

Approximately 700 patients will be randomized in a 1:1 ratio between axitinib vs placebo.

Eligibility criteria: Inclusion Criteria:

Patients must be treated by nephrectomy and patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial:

1. Patients must have no evidence of macroscopic residual disease or metastatic disease.
2. Male or female, age \>=18 years (age \>=20 years in Japan, Korea and Taiwan).
3. Patients must be diagnosed with one of the following based on American Joint Committee on Cancer (AJCC) TNM staging version 2010, Eastern Collaborative Oncology Group (ECOG) performance status (PS):

   * pT2, pN0 or pNx, M0 and ECOG PS 0-1
   * pT3, pN0 or pNx, M0 and ECOG PS 0-1
   * pT4, pN0 or pNx, M0 and ECOG PS 0-1
   * Any pT, pN1, M0 and ECOG PS 0-1
4. Patients must have histologically confirmed preponderant, defined as \>50%, clear cell RCC.
5. Patients must not have received any previous systemic (includes chemotherapeutic, hormonal, or immunotherapeutic) treatment for RCC.
6. Patients must not have received any previous anti angiogenic treatment.
7. Patients must have adequate organ function.

Exclusion Criteria

1. Histologically undifferentiated carcinomas, sarcomas, collecting duct carcinoma, lymphoma, or patients with any metastatic renal sites.
2. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage \<4 weeks of date of randomization.
3. Diagnosis of any non-RCC malignancy within the 5 years from date of randomization, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated with no evidence of recurrent disease for 12 months.
4. Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism.
5. Gastrointestinal abnormalities

Primary outcomes:
measure: Disease Free Survival (DFS) as Assessed by Blinded Independent Review Committee (IRC)
timeFrame: From randomization date up to first date of recurrence or the occurrence of a secondary malignancy or death (up to 5 years)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization date until death due to any cause (up to 5 years)
measure: Number of Participants With Treatment-Emergent Adverse Events (AE) and Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to 28 days after last dose (maximum duration of 3 years)
measure: Number of Participants With Treatment-Emergent Treatment Related Adverse Events and Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to 28 days after last dose (maximum duration of 3 years)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity
timeFrame: From Day 1 up to 28 days after last dose (maximum duration of 3 years)
measure: Number of Participants With Laboratory Abnormalities By Maximum CTCAE Grade: Hematology
timeFrame: From Day 1 up to 28 days after last dose (maximum duration of 3 years)
measure: Number of Participants With Laboratory Abnormalities By Maximum CTCAE Grade: Chemistry
timeFrame: From Day 1 up to 28 days after last dose (maximum duration of 3 years)
measure: Number of Participants With Laboratory Abnormalities: Thyroid Function
timeFrame: From Day 1 up to 28 days after last dose (maximum duration of 3 years)
measure: Number of Participants With Laboratory Abnormalities: Urinalysis
timeFrame: From Day 1 up to 28 days after last dose (maximum duration of 3 years)
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Pleasant Hill
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Ocala
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Annapolis
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Saint Paul
country: United States
state: Minnesota
city: Omaha
country: United States
state: Nebraska
city: Hackensack
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: New York
country: United States
state: New York
city: Portland
country: United States
state: Oregon
city: Charleston
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Bedford
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Norfolk
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Beijing
country: China
city: Changchun
country: China
city: Chongqing
country: China
city: Dalian
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Jinan
country: China
city: Nanchang
country: China
city: Shanghai
country: China
city: Suzhou
country: China
city: Tianjin
country: China
city: Wuhan
country: China
city: Besançon
country: France
city: Bordeaux Cedex
country: France
city: Hyères
country: France
city: Le Mans Cedex 02
country: France
city: Lyon
country: France
city: Marseille cedex 5
country: France
city: Paris Cedex 15
country: France
city: Rennes Cedex
country: France
city: Saint Herblain
country: France
city: Suresnes Cedex
country: France
city: Vandoeuvre les Nancy Cedex
country: France
city: Hong Kong
country: Hong Kong
city: Ahmeadbad
country: India
city: Aurangabad
country: India
city: Bangalore
country: India
city: Chennai
country: India
city: Hyderabad
country: India
city: Karamsad
country: India
city: Kochi
country: India
city: Kolkota
country: India
city: Lucknow
country: India
city: Ludhiana
country: India
city: Mangalore
country: India
city: Manipal
country: India
city: Mumbai
country: India
city: Nashik
country: India
city: New Delhi
country: India
city: Pune
country: India
city: Surat
country: India
city: Vishakhapatnam
country: India
city: Aichi
country: Japan
city: Akita
country: Japan
city: Aomori
country: Japan
city: Chiba
country: Japan
city: Fukuoka
country: Japan
city: Gifu
country: Japan
city: Hokkaido
country: Japan
city: Hyogo
country: Japan
city: Kagawa
country: Japan
city: Kanagawa
country: Japan
city: Kumamoto
country: Japan
city: Kyoto
country: Japan
city: Nagasaki
country: Japan
city: Nigata
country: Japan
city: Osaka
country: Japan
city: Shizuoka
country: Japan
city: Tokushima
country: Japan
city: Tokyo
country: Japan
city: Yamagata
country: Japan
city: Yamaguchi,
country: Japan
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Gyeonggi
country: Korea, Republic of
city: Jeonnam
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Barcelona
country: Spain
city: Leganes
country: Spain
city: Llobregat
country: Spain
city: Madrid
country: Spain
city: Oviedo
country: Spain
city: San Sebastian
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
Study officials:
References:
citation: Gross-Goupil M, Kwon TG, Eto M, Ye D, Miyake H, Seo SI, Byun SS, Lee JL, Master V, Jin J, DeBenedetto R, Linke R, Casey M, Rosbrook B, Lechuga M, Valota O, Grande E, Quinn DI. Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial. Ann Oncol. 2018 Dec 1;29(12):2371-2378. doi: 10.1093/annonc/mdy454.