Study of Axitinib for Reducing Extent of Venous Tumour Thrombus in Renal Cancer With Venous Invasion

NCT03494816

Last updated date
Study Location
Addenbrookes Hospital
Cambridge, , CB2 0QQ, United Kingdom
Contact
0131 275 6727

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Non-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. Age ≥ 18. 2. Histologically proven clear cell RCC. 3. Immediate resection of the primary tumour considered technically possible. 4. Suitable for and willing to undergo nephrectomy (either cytoreductive or with curative intent) 4. cT3b, cT3c, cT3a (main renal vein) 5. N0, N1, or Nx 6. M0, or M1 7. ECOG performance status 0 - 1 8. Urinalysis <2+ protein. If dipstick is ≥2+ then a 24-hour urine collection should be performed and the patient may enter NAXIVA only if urinary protein is <2g per 24 hours.

9. All female patients with reproductive potential must have a negative serum or urine pregnancy test within a maximum of 14 days prior to starting trial treatment.

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


1. For M1 patients: poor risk on Memorial Sloan Kettering Cancer Centre (MSKCC) score and
deemed suitable for cytoreductive nephrectomy at time of enrolment.


2. The presence of active second malignancy. Patients will be eligible if they have
adequately treated basal cell carcinoma, squamous cell skin cancer, in situ cervical
cancer, stable prostate cancer or if treated with curative intent for any other cancer
with no evidence of disease for 2 years. Patients with prostate cancer will be
permitted entry if not receiving treatment and prostrate-specific antigen (PSA) is not
rising.


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 and up to 1 week after treatment.


Male patients must be surgically sterile or must agree to use effective contraception
during the period of therapy and for 6 months after completion of study drug (Patients
who do not meet this will not be are not eligible).


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


5. Gastrointestinal abnormalities including: a. inability to take oral medication; b.
requirement for intravenous alimentation; c. prior surgical procedures affecting
absorption including total gastric resection; d. treatment for active peptic ulcer
disease in the past 6 months; e. 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; f.
malabsorption syndromes.


6. Current use or anticipated need for treatment with drugs that are known potent CYP3A4
inhibitors (see section 4.4, concomitant therapy).


7. Current use, or anticipated need for treatment with, drugs that are known CYP3A4
inducers or substrates for CYP1A2 (see section 4.4, concomitant therapy).


8. 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.


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


10. 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.


11. Uncontrolled hypertension (>160/100 mmHg despite optimised antihypertensive
treatment).


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


13. ALT or AST ≥ 1.5 x ULN; Bilirubin ≥ 1.5 x ULN.


14. Serum creatinine ≥ 1.5 x ULN


15. Neutrophil count < 1.0 x 109/L; platelet count < 100 x 109/L; Hb ≤ 90g/L.


16. Known severe hepatic impairment (Child-Pugh class C)


17. Known hypersensitivity to axitinib or any of its excipients. Specifically patients
with hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose
malabsorption should not enter the study.

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Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Non-metastatic Renal Cell CarcinomaStudy of Axitinib for Reducing Extent of Venous Tumour Thrombus in Renal Cancer With Venous Invasion
NCT03494816
  1. Cambridge,
  2. Edinburgh,
  3. Glasgow,
  4. London,
  5. London,
  6. Manchester,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Study of Axitinib for Reducing Extent of Venous Tumour Thrombus in Renal Cancer With Venous Invasion
Official Title  ICMJE NAXIVA- Phase II Neoadjuvant Study of Axitinib for Reducing Extent of Venous Tumour Thrombus in Clear Cell Renal Cell Cancer With Venous Invasion
Brief Summary

NAXIVA is a study of axitinib in patients with metastatic and non-metastatic renal cell carcinoma with venous invasion. Patients will be given axitinib (twice daily) for 8 weeks (at an escalated dose) and the response of the venous invasion will be assessed.

Blood, urine and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response.

The primary objective is to assess the response of the thrombus to axitinib. Its thought that axitinib will reduce the extent of the thrombus in the inferior vena cava will reduce the extent of surgical intervention.

Detailed Description

NAXIVA is a single arm, single agent, open label, phase II feasibility study of axitinib in patients with both metastatic and non-metastatic renal cell carcinoma of clear cell histology. 20 patients will be recruited from multiple centres within the United Kingdom.

Patients who have signed informed consent and who have met all eligibility criteria will be registered into the trial.

The starting dose of axitinib will be 5mg BID and escalated to 7mg BID and then 10mg BID. A dose modification assessment will take place every 2 weeks in clinic during the 8 week pre-surgical treatment period and will be dependent on tolerability of treatment. Patients will follow an aggressive axitinib dose escalation process within the 8 week period to a maximum of 10mg BID. Patients should stop axitinib a minimum of 36 hours and a maximum of 7 days prior to surgery in week 9.

Blood, urine and tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. Nephrectomy and IVC tumour thrombectomy will be planned for all patients on the trial.

Response to axitinib in VTT, primary tumour and any RECIST measureable lesion will be correlated with changes in molecular markers.

Patients will be followed up in clinic at 6 & 12 weeks post surgery.

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
  • Renal Cell Carcinoma
  • Metastatic Renal Cell Carcinoma
  • Non-metastatic Renal Cell Carcinoma
Intervention  ICMJE Drug: Axitinib Oral Tablet

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 and blood pressure.

Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day with or without food as per instruction. On clinic days only, patients will be advised to fast for 6 hours prior to their clinic visit.

Patients should be advised to stop axitinib treatment a minimum of 36 hours and maximum of 7 days prior to week 9 nephrectomy and thrombectomy surgery.

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 Names:
  • Inlyta
  • AG-013736
Study Arms  ICMJE Experimental: Axitinib
Axitinib - oral tablet twice daily for 8 weeks prior to surgery. Starting dose 5mg.
Intervention: Drug: Axitinib Oral Tablet
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 Completed
Actual Enrollment  ICMJE
 (submitted: October 20, 2020)
21
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2018)
20
Actual Study Completion Date  ICMJE June 10, 2020
Actual Primary Completion Date March 3, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

1. Age ? 18. 2. Histologically proven clear cell RCC. 3. Immediate resection of the primary tumour considered technically possible. 4. Suitable for and willing to undergo nephrectomy (either cytoreductive or with curative intent) 4. cT3b, cT3c, cT3a (main renal vein) 5. N0, N1, or Nx 6. M0, or M1 7. ECOG performance status 0 - 1 8. Urinalysis <2+ protein. If dipstick is ?2+ then a 24-hour urine collection should be performed and the patient may enter NAXIVA only if urinary protein is <2g per 24 hours.

9. All female patients with reproductive potential must have a negative serum or urine pregnancy test within a maximum of 14 days prior to starting trial treatment.

Exclusion Criteria:

  1. For M1 patients: poor risk on Memorial Sloan Kettering Cancer Centre (MSKCC) score and deemed suitable for cytoreductive nephrectomy at time of enrolment.
  2. The presence of active second malignancy. Patients will be eligible if they have adequately treated basal cell carcinoma, squamous cell skin cancer, in situ cervical cancer, stable prostate cancer or if treated with curative intent for any other cancer with no evidence of disease for 2 years. Patients with prostate cancer will be permitted entry if not receiving treatment and prostrate-specific antigen (PSA) is not rising.
  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 and up to 1 week after treatment.

    Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy and for 6 months after completion of study drug (Patients who do not meet this will not be are not eligible).

  4. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine or pulmonary disease other than directly related to RCC.
  5. Gastrointestinal abnormalities including: a. inability to take oral medication; b. requirement for intravenous alimentation; c. prior surgical procedures affecting absorption including total gastric resection; d. treatment for active peptic ulcer disease in the past 6 months; e. 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; f. malabsorption syndromes.
  6. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 4.4, concomitant therapy).
  7. Current use, or anticipated need for treatment with, drugs that are known CYP3A4 inducers or substrates for CYP1A2 (see section 4.4, concomitant therapy).
  8. 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.
  9. Active seizure disorder, spinal cord compression, or carcinomatous meningitis.
  10. 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.
  11. Uncontrolled hypertension (>160/100 mmHg despite optimised antihypertensive treatment).
  12. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
  13. ALT or AST ? 1.5 x ULN; Bilirubin ? 1.5 x ULN.
  14. Serum creatinine ? 1.5 x ULN
  15. Neutrophil count < 1.0 x 109/L; platelet count < 100 x 109/L; Hb ? 90g/L.
  16. Known severe hepatic impairment (Child-Pugh class C)
  17. Known hypersensitivity to axitinib or any of its excipients. Specifically patients with hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not enter the study.
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 NCT03494816
Other Study ID Numbers  ICMJE NAXIVA
2017-000619-17 ( EudraCT Number )
ISRCTN96273644 ( Other Identifier: ISRCTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Scottish Clinical Trials Research Unit
Study Sponsor  ICMJE Scottish Clinical Trials Research Unit
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Grant D StewartUniversity of Cambridge
PRS Account Scottish Clinical Trials Research Unit
Verification Date October 2020

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