Phase 3 study of sunitinib versus placebo in subjects at high risk of recurrent kidney cancer

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2006-004024-37-GB
• Date of registration: 15/05/2007
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, 10017
• Public title: Phase 3 study of sunitinib versus placebo in subjects at high risk of recurrent kidney cancer
• Scientific title: SUNITINIB TREATMENT OF RENAL ADJUVANT CANCER (S-TRAC): A RANDOMIZED DOUBLE-BLIND PHASE 3 STUDY OF ADJUVANT SUNITINIB VS. PLACEBO IN SUBJECTS AT HIGH RISK OF RECURRENT RRC - S-TRAC
• Date of first enrolment: 09/10/2007
• Target sample size: 619
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004024-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Canada, China, Colombia, Czech Republic, Denmark, France, Germany, Greece, Ireland, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Poland, Slovakia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov Callcenter
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Callcenter
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1.Subjects must sign and date IRB/IEC approved informed consent;
2.Age =18 years;
3.ECOG Performance Status 0 – 2 prior to nephrectomy;
4.Subjects must be diagnosed utilizing the UISS staging system with one of the following:
a.T3 N0 or Nx, M0, any Fuhrman’s grade and any ECOG general status; or
b.T4 N0 or Nx, M0, any Fuhrman’s grade and any ECOG general status; or
c.Any T, N1 2, M0, any Fuhrman’s grade and any ECOG general status.
5.Subjects must have histologically confirmed preponderant, defined as >50%, clear cell RCC;
6.Subjects must have no evidence of macroscopic residual disease or metastatic disease. Subjects having evidenceof microscopic disease (Histological classification of R1 disease) are acceptable;
7.Subjects must not have received any previous systemic (includes chemotherapeutic, hormonal, or immunotherapeutic) treatment for RCC;
8.Subjects must not have received any previous anti angiogenic treatment;
9.Subjects must receive the first oral dose of sunitinib not more than 12 weeks after date of nephrectomy
10.Subjects must have adequate organ function defined as:
a.Platelets =75 x 109/L, hemoglobin = 8 g/dl, absolute neutrophil count (ANC) =1.5 x 109/L;
b.Bilirubin =3 mg/dL (known Gilbert’s exempt from this criteria), aspartate transaminase (AST) and alanine transaminase (ALT) =2.5 times the upper limit of normal (ULN);
c.Calculated creatinine clearance =30 ml/min post-nephrectomy as determined by the Cockcroft and Gault Equation (listed in the Q&A document posted to the Insight space for all PCO managers);
11.Women and men must use adequate contraception during the study. Acceptable contraception for women include implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence, or a partner who has been vasectomized for at least 6 months. Acceptable contraception for a male includes having had a vasectomy for at least 6 months, sexual abstinence, or condoms plus spermicide;
12.UK and IRELAND ONLY. Women and men must use adequate contraception during the study. Adequate contraception is defined as double barrier contraception (ie, condom plus spermicide in combination with a female condom, diaphragm, cervical cap or intrauterine device).
13.Left ventricular ejection fraction (LVEF) = the lower limit of normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO);
14.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 427
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 192

Exclusion criteria:
1.Histologically undifferentiated carcinomas, sarcomas, collecting duct carcinoma, lymphoma, or subjects with any metastatic renal sites;
2.NCI CTCAE Grade 3 hemorrhage <4 weeks of date of randomization;
3.Diagnosis of any second 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 6 months prior to study drug administration: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism;
5.Concurrent medication with known CYP3A4 inducers and potent inhibitors dosed 7 and 12 days before date of randomization, respectively
6.Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2 or prolongation of the QTc interval to >500 msec;
7.Hypertension, defined as systolic >150 and/or diastolic >100, that cannot be controlled by medications;
8.Treatment with >2 mg of warfarin within 2 weeks prior to first day or concurrently with sunitinib administration is not recommended. Low dose warfarin for deep vein thrombosis (DVT) prophylaxis is permitted (<2 mg/day). Low molecular weight heparin (fractionated) or aspirin are allowed;
9.Any illness that may affect absorption, including but not limited to: inability to swallow oral medications, presence of active inflammatory bowel disease, partial or complete bowel obstruction, partial or complete gastrectomy, significant bowel resection, or chronic diarrhea;
10.Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness;
11.Known active or chronic active hepatitis (Hepatitis B or C);
12. Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outline in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product;
13.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study;
14.Receipt of any investigational oncology or, approved or investigational anti angiogenic agent prior to study entry;
15.Current treatment on another therapeutic clinical trial. Supportive care trials or non treatment trials, eg, PRO methods studies, are allowed.
16. Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Adjuvant treatment of subjects with “high risk” Renal Cell Carcinoma (RCC) following nephrectomy.
MedDRA version: 11.0 Level: HLT Classification code 10038408 Term: Renal cell carcinomas System Organ Class: 100000004864

Intervention(s)

Trade Name: Sutent
Product Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 341031-54-7
Current Sponsor code: SU-0011248
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Sutent
Product Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 341031-54-7
Current Sponsor code: SU-0011248
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Sutent
Product Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
CAS Number: 341031-54-7
Current Sponsor code: SU-0011248
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 37.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: •Compare overall survival (OS) associated with Arm A to that associated with Arm B;
•Assess safety/toxicity profile of schedule 4/2 administration of sunitinib;
•Assess patient reported outcomes (PROs);
•Assess the UISS Prognostic Model

Timepoint(s) of evaluation of this end point: Disease Free Survival: (DFS), time interval from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. For subjects with no DFS event, DFS time censored at date of last disease assessment prior to time for final analysis. Subjects alive who do not have post baseline disease assessment will have their DFS times censored at randomization. For subjects receiving further anti tumor therapy prior to disease recurrence or occurrence of a secondary malignancy or death, DFS will be censored on the date of the last tumor assessment prior to taking the anti tumor medication.

Primary end point(s): Disease Free Survival: (DFS), defined as the time interval from the date of randomization to the first date of recurrence or the occurrence of a secondary malignancy or death. The primary DFS analysis will be based on independent blinded third-party review. A secondary analysis of DFS will be based on the local investigator assessment. Recurrence refers to relapse of the primary tumor in situ or at metastatic sites. The date of recurrence or the occurrence of a secondary malignancy is defined as the date of the tumor assessment that demonstrated unequivocal recurrence or a second malignancy according to protocol criteria and is confirmed by independent, blinded third party review. For subjects with no DFS event, DFS time will be censored at the date of last disease assessment prior to the time of the final analysis. Subjects alive who do not have post baseline disease assessment will have their DFS times censored at randomisation. For subjects receiving further anti tumor therapy prior to disease recurrence or occurrence of a secondary malignancy or death, DFS will be censored on the date of the last tumor assessment prior to taking the anti tumor medication.

Main Objective: To demonstrate an improvement in disease free survival (DFS) in subjects at the highest (per modified UISS criteria) risk of disease recurrence with RCC randomly assigned to adjuvant sunitinib 50 mg schedule 4/2 for 1 year (9 cycles) (Arm A) vs. Placebo (Arm B) after nephrectomy

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1- Overall Survival (OS) time from the date of randomization to the date of death due to any cause. In absence of confirmation of death, survival time will be censored at last date the subject is known alive. Subjects lacking data beyond randomization will have their survival times censored at randomization. 2- Type, incidence, severity (graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, timing, seriousness, and relatedness of adverse events and laboratory abnormalitiesonship. 3- Patient reported outcomes (PROs), at end of study

Secondary end point(s): • Overall Survival (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 will be censored at the last date the subject is known to be alive. Subjects lacking data beyond randomization will have their survival times censored at randomization.
• Type, severity (graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 3.0 dated 09 August 2006), seriousness, and relatedness of adverse events, and laboratory abnormalities;
• Patient reported outcomes (PROs), defined as health related quality of life using the self administered European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (EORTC QLQ-C30) and health status using the EuroQoL Group EQ-5D questionnaire (EQ-5D). The questionnaires will be completed on Day 1 or approximately every 6 weeks, prior to having any tests or receiving any treatment up to the end of study treatment with sunitinib or placebo.

Secondary ID(s)

2006-004024-37-FR

A6181109

Source(s) of Monetary Support

Pfizer Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 23/03/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-004024-37/results