A study of axitinib compared to placebo in the treatment of patients with renal cell carcinoma (kidney cancer)

Phase 1

• Conditions: Renal Cell Carcinoma; MedDRA version: 16.1Level: LLTClassification code 10038415Term: Renal cell carcinoma stage unspecifiedSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003905-24-ES
• Lead Sponsor: SFJ Pharma Ltd. II

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-13
• Last Update Posted: 30 April 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 592

Inclusion Criteria

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, age ?18 years and ? 65 years in India).
3. Patients must be diagnosed with one of the following based on American Joint Committee on Cancer (AJCC) TNM staging version 2010 29, Eastern Collaborative Oncology Group (ECOG) performance status (PS). Any Fuhrman grades are eligible. The patient subgroups will be as follows:
a. pT2, pN0 or pNx, M0 and ECOG PS 0-1
b. pT3, pN0 or pNx, M0 and ECOG PS 0-1
c. pT4, pN0 or pNx, M0 and ECOG PS 0-1
d. 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 defined as:
? Absolute neutrophil count (ANC) ?1500 cells/mm3.
? Platelets ?75,000 cells/mm3.
? Hemoglobin (Hgb) ?9.0 g/dL.
? AST and ALT ?2.5 x upper limit of normal (ULN).
? Total bilirubin ?1.5 x ULN.
? Serum creatinine (Scr) ?1.5 x ULN or calculated creatinine clearance (Clcr) ?60 mL/min (by the Cockcroft-Gault equation*).
* For males; the Cockcroft-Gault equation, using Scr : Clcr (mL/min) = (140 - Age in years) × weight (in kilograms) / [72 × Scr (in mg/dL)]
The calculated Clcr should be multiplied by 0.85 to adjust for female gender.
? Urinary protein <2+ by urine dipstick. If dipstick is ?2+ then a urine protein: urine creatinine ratio (UPC) should be done and the patient may enter only if UPC is < 2.0.

8. At screening, no evidence of preexisting uncontrolled hypertension as documented by 2 blood pressure (BP) readings taken at least 1 hour apart in the seated position after the patient has been sitting quietly for 5 minutes. The systolic blood pressure (sBP) readings must be ?140 mm Hg, and the diastolic blood pressure (dBP) readings must be ?90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
9. Women of childbearing potential and men must use adequate contraception during the study and for 6 months after discontinuing or completing study treatment. 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.
10. Signed and dated informed consent document (ICD) indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
11. 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 296
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 296

Exclusion Criteria

1. Histologically undifferentiated carcinomas, sarcomas, collecting duct carcinoma, lymphoma, or patients with any metastatic renal sites.
2. Active bleeding (other than menstrual bleeding) at 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 including:
? inability to take oral medication
? requirement for intravenous alimentation
? prior surgical procedures affecting absorption including total gastric resection
? treatment for active peptic ulcer disease in the past 6 months
? active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
? malabsorption syndromes
? chronic diarrhea that persists at Grade 3 or 4 despite maximal medical therapy

6. Major surgery <4 weeks, or radiation theapy <2 weeks, of starting the study treatment or incomplete healing of surgical or superficial wounds.
7. Current use or anticipated need for treatment with drugs that are known potent CYP3A4/5 inhibitors (eg, grapefruit juice, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin).
8. Current use or anticipated need for treatment with drugs that are known CYP3A4/5 or CYP1A2 inducers (eg, rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, and St. John?s wort).
9. Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose warfarin and other low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
10. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
11. A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
12. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
13. Pregnancy or breastfeeding. Urinary pregnancy test should be performed by sites on female patients who have not experienced at least one consecutive year of amenorrhea without ovarian dysfunction, or have been taking hormonal therapy, or have been rendered surgically sterile. If positive, serum pregnancy test should be performed at central laboratories. All female patients of childbearing potential must have a negative pregnancy test within the 14 days prior to date of randomization. (Definition of surgical sterilization: patients who underwent hysterectomy or bilateral oophorectomy, or bilateral tubal ligation)
14. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
15. Other severe acute or chronic medical or psychiatri

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified