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A-PREDICT: A Phase II Study Of Axitinib In Metastatic Renal Cell Cancer in Patients Unsuitable for Nephrectomy

Phase 2
18 Years
Open (Enrolling)
Clear-cell Metastatic Renal Cell Carcinoma

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Trial Information

A-PREDICT: A Phase II Study Of Axitinib In Metastatic Renal Cell Cancer in Patients Unsuitable for Nephrectomy

A-PREDICT is a single arm, single agent, open label, multicentre, phase II study of axitinib
in patients with metastatic renal cell carcinoma of predominant clear cell histology and
unsuitable for debulking nephrectomy (as judged by the treating clinician). Patients who
have provided consent and have satisfied the eligibility criteria will be registered into
the trial.

The starting dose of axitinib will be 5 mg twice daily by mouth, escalating to a maximum of
10mg twice daily by mouth according to tolerability of treatment, for as long as patients
are deriving clinical benefit. Treatment will be paused for one week prior to percutaneous
biopsy of the primary on day 1 week 9. Disease progression will be evaluated according to
RECIST v1.1 criteria 8 weeks after commencing treatment, at 8 weekly intervals to 6 months
and 3 monthly thereafter. Blood and tumour tissue samples will be taken prior to and during
therapy to evaluate biomarkers of treatment response. Nephrectomy will be carried out on any
patient who becomes suitable in the opinion of the treating clinician during the course of
the trial. Where possible, tissue samples will be taken from resected specimens. Response to
axitinib in marker lesions will be correlated with changes in biomarkers.

Inclusion Criteria:

1. Histologically confirmed metastatic renal cell carcinoma of predominant clear cell

2. Unsuitable for nephrectomy

3. Unsuitable for 'watch and wait' policy

4. No prior systemic therapy for renal cell carcinoma

5. Measurable metastatic disease using RECIST v1.1

6. Life expectancy 12 weeks or greater

7. ECOG performance status 0 or 1

8. Adequate organ function as defined by serum aspartate transaminase (AST) and serum
alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN), or AST and ALT ≤5 x
ULN if liver function abnormalities are due to liver metastases; total serum
bilirubin ≤1.5 x ULN

9. Adequate haematological function as defined by absolute neutrophil count (ANC)
≥1500/μL, platelets ≥75,000/μL, haemoglobin ≥9.0 g/dL and prothrombin time (PT) ≤1.5

10. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min;

11. Urinary protein <2+ by urine dipstick.

12. No evidence of pre-existing uncontrolled hypertension

13. Women of childbearing potential must have a negative serum or urine pregnancy test
within 3 days prior to treatment.

14. Willingness and ability to comply with study procedures, including tumour biopsies.

15. Written informed consent

Exclusion Criteria:

1. The presence of intracranial disease, unless stable >6 months. In the case of a
solitary brain metastasis which has been resected, there must be evidence of a
disease-free interval of at least 3 months post-surgery. All patients previously
treated for brain metastases must be stable off corticosteroid therapy for at least
28 days.

2. The presence of active second malignancy.

3. Women who are pregnant or are breastfeeding. Female patients must be surgically
sterile, be postmenopausal, or must agree to use effective contraception during the
period of therapy.

4. Male patients must be surgically sterile or must agree to use effective contraception
during the period of therapy.

5. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine,
pulmonary disease other than directly related to RCC.

6. Gastrointestinal abnormalities including:

1. inability to take oral medication;

2. requirement for intravenous alimentation;

3. prior surgical procedures affecting absorption including total gastric

4. treatment for active peptic ulcer disease in the past 6 months;

5. 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;

6. malabsorption syndromes.

7. Current use or anticipated need for treatment with drugs that are known potent CYP3A4
inhibitors (see section 8.12, concomitant therapy).

8. Current use or anticipated need for treatment with drugs that are known CYP3A4 or
CYP1A2 inducers (see section 8.12, concomitant therapy).

9. Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose
anticoagulants for maintenance of patency of central venous access device or
prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular
weight heparin is allowed.

10. Active seizure disorder, spinal cord compression, or carcinomatous meningitis.

11. Any of the following within 12 months prior to study entry: myocardial infarction,
uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive
heart failure, cerebrovascular accident or transient ischemic attack.

12. Deep vein thrombosis or pulmonary embolism within 6 months prior to study entry.

13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Freedom from progression at 6 months

Outcome Description:

The proportion of study participants alive and progression free at 6 months (day 1 week 25 visit). Progression will be measured from the date of study entry (registration date) until the first date of either death or confirmed progressive disease according to RECIST. Patients alive and free from progression will be censored at the date of last follow-up. The proportion of patients progression free at 6 months will be reported with 95% confidence interval. In addition, progression free survival will be presented using the Kaplan Meier product limit method with median progression free survival reported. A blinded central review of CT scans will be conducted for verification purposes.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

James Larkin

Investigator Role:

Principal Investigator

Investigator Affiliation:

Royal Marsden Hospital, London


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

October 2012

Completion Date:

September 2016

Related Keywords:

  • Clear-cell Metastatic Renal Cell Carcinoma
  • metastatic renal cell carcinoma
  • predominant clear cell histology
  • Unsuitable for nephrectomy
  • unsuitable for 'watch and wait' policy
  • Carcinoma
  • Carcinoma, Renal Cell