A Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy

NCT01693822

Last updated date
Study Location
Royal Marsden Hospital - sutton
London, Sutton, SM2 5PT, United Kingdom
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Clear-cell Metastatic Renal Cell Carcinoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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

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) or 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 x ULN

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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 resection;


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.


14. Known galactose intolerance, Lapp lactase deficiency or glucose-galactose
malabsorption

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Clear-cell Metastatic Renal Cell CarcinomaA Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy
NCT01693822
  1. London, Sutton
  2. Cambridge,
  3. London,
  4. Manchester,
  5. Plymouth,
  6. Surrey,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE A Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy
Official Title  ICMJE A-PREDICT: A Phase II Study Of Axitinib In Metastatic Renal Cell Cancer in Patients Unsuitable for Nephrectomy
Brief Summary A-PREDICT is a study of axitinib in patients with metastatic renal cell carcinoma unsuitable for nephrectomy (as judged by the treating clinician) to evaluate efficacy, safety, toxicity and changes in biomarkers during therapy. Axitinib will given twice daily by mouth according to tolerability of treatment, for as long as patients are deriving clinical benefit. Blood and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. The primary clinical objective of this study is to define the activity of axitinib given to patients with metastatic renal cell carcinoma unsuitable for nephrectomy.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Clear-cell Metastatic Renal Cell Carcinoma
Intervention  ICMJE Drug: Axitinib

Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities.

Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy.

Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day.

Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.

Other Name: AG-013736
Study Arms  ICMJE Experimental: Axitinib
Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg.
Intervention: Drug: Axitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 24, 2012)
99
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed metastatic renal cell carcinoma of predominant clear cell histology
  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) or 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/?L, platelets ?75,000/?L, haemoglobin ?9.0 g/dL and prothrombin time (PT) ?1.5 x ULN
  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 resection;
    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.
  14. Known galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01693822
Other Study ID Numbers  ICMJE ICR-CTSU/2011/10033
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Institute of Cancer Research, United Kingdom
Study Sponsor  ICMJE Institute of Cancer Research, United Kingdom
Collaborators  ICMJE
  • Pfizer
  • Royal Marsden NHS Foundation Trust
Investigators  ICMJE
Principal Investigator:James LarkinRoyal Marsden Hospital, London
PRS Account Institute of Cancer Research, United Kingdom
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP