Adjuvant Axitinib Therapy of Renal Cell Cancer in High Risk Patients (ATLAS)

• ClinicalTrials.gov Identifier: NCT01599754
• Recruitment Status: Terminated
• First Posted: May 16, 2012
• Results First Posted: August 26, 2019
• Last Update Posted: September 20, 2019
• Sponsor: SFJ Pharma Ltd. II
• Collaborators: Pfizer; SFJ Pharmaceuticals, Inc.
• Information provided by (Responsible Party): SFJ Pharmaceuticals, Inc. ( SFJ Pharma Ltd. II )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Clear Cell Renal Carcinoma	Drug: Axitinib; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 724 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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 Start Date: April 2012
• Actual Primary Completion Date: October 10, 2017
• Actual Study Completion Date: May 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Axitinib	Drug: Axitinib; Axitinib 5 mg twice daily; Other Name: Inlyta
Placebo Comparator: Placebo	Drug: Placebo; Placebo twice daily

Outcome Measures

Primary Outcome Measures :

1. Disease Free Survival (DFS) as Assessed by Blinded Independent Review Committee (IRC) [ Time Frame: From randomization date up to first date of recurrence or the occurrence of a secondary malignancy or death (up to 5 years) ]
   DFS is defined as time interval from the date of randomization to first date of recurrence/relapse (distant or local recurrence of [RCC] or occurrence of a secondary malignancy {occurrence of a second primary cancer other than RCC} or death). For participants with no DFS event, DFS was censored at date of last scan prior to time of analyses. Participants alive who did not have post-baseline disease assessments, DFS was censored at randomization. Participants who received further anti-tumor therapy prior to recurrence or occurrence of a secondary malignancy or death, DFS was censored on date of last scan prior to taking anti-tumor medication. Participants who missed 2 or more consecutive tumor scans immediately followed by an event were censored at date of last objective tumor assessment prior to missing/not readable scan.

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: From randomization date until death due to any cause (up to 5 years) ]
   OS defined as the time from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. Participants lacking data beyond randomization had their survival times censored at randomization.
2. Number of Participants With Treatment‑Emergent Adverse Events (AE) and Serious Adverse Events (SAEs) [ Time Frame: From Day 1 up to 28 days after last dose (maximum duration of 3 years) ]
   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events.
3. Number of Participants With Treatment‑Emergent Treatment Related Adverse Events and Serious Adverse Events (SAEs) [ Time Frame: From Day 1 up to 28 days after last dose (maximum duration of 3 years) ]
   A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.
4. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity [ Time Frame: From Day 1 up to 28 days after last dose (maximum duration of 3 years) ]
   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).
5. Number of Participants With Laboratory Abnormalities By Maximum CTCAE Grade: Hematology [ Time Frame: From Day 1 up to 28 days after last dose (maximum duration of 3 years) ]
   Hematology parameters included anemia, hemoglobin increased, lymphocyte count increased, lymphocyte count decreased, neutrophil count decreased, platelet count decreased, and white blood cell count decreased. CTCAE grades: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).
6. Number of Participants With Laboratory Abnormalities By Maximum CTCAE Grade: Chemistry [ Time Frame: From Day 1 up to 28 days after last dose (maximum duration of 3 years) ]
   Chemistry parameters included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase increased, creatinine increased, hypoalbuminemia, hypercalcemia, hypocalcemia, hyperglycemia, hypoglycemia, hyperkalemia, hypokalemia, hypernatremia, hyponatremia. CTCAE grades: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).
7. Number of Participants With Laboratory Abnormalities: Thyroid Function [ Time Frame: From Day 1 up to 28 days after last dose (maximum duration of 3 years) ]
   Number of participants with thyrotropin levels: <5 milli-international units per litre (mIU/L), >=5 to <10 mIU/L, >=10 mIU/L are reported.
8. Number of Participants With Laboratory Abnormalities: Urinalysis [ Time Frame: From Day 1 up to 28 days after last dose (maximum duration of 3 years) ]
   Number of participants with urine protein dipstick grading: negative/trace (5 to 20 milligram per deciliter [mg/dL]), 1+ (30 mg/dL]), 2+ (100 mg/dL), 3+ (300 mg/dL) and 4+ (more than 1000 mg/dL) are reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

  Show 106 Study Locations

Sponsors and Collaborators

SFJ Pharma Ltd. II

Pfizer

SFJ Pharmaceuticals, Inc.

  Study Documents (Full-Text)

Documents provided by SFJ Pharmaceuticals, Inc. ( SFJ Pharma Ltd. II ):

Statistical Analysis Plan  [PDF] March 6, 2018

Study Protocol  [PDF] March 21, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: SFJ Pharma Ltd. II
• ClinicalTrials.gov Identifier: NCT01599754 History of Changes
• Other Study ID Numbers: AP311736
• First Posted: May 16, 2012
• Results First Posted: August 26, 2019
• Last Update Posted: September 20, 2019
• Last Verified: September 2019

Keywords provided by SFJ Pharmaceuticals, Inc. ( SFJ Pharma Ltd. II ):

renal cell carcinoma; axitinib; tyrosine kinase inhibitor

Additional relevant MeSH terms:

Carcinoma, Renal Cell; Kidney Neoplasms; Carcinoma; Kidney Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Axitinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action