Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01263769
First received: December 17, 2010
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

The goal of this clinical research study is to learn if axitinib can help to control kidney cancer. The safety of this drug will also be studied.


Condition Intervention Phase
Kidney Cancer
Drug: Axitinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial Examining the Impact Of Neoadjuvant Axitinib On Primary Tumor Response In Patients With Locally Advanced Clear Cell Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Objective response rate (ORR) is defined as CR+PR and evaluated when CT abdomen is done after 12 weeks of treatment. Where using RECIST criteria, Complete Response (CR) is complete disappearance of renal mass; and, Partial Response (PR) is at least a 30% decrease in the largest diameter (LD) of the renal mass taking as reference the baseline largest diameter.


Estimated Enrollment: 40
Study Start Date: February 2011
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Axitinib
Axitinib Starting dose: 5 mg by mouth twice each day for 12 weeks.
Drug: Axitinib
Starting dose: 5 mg by mouth twice each day for 12 weeks.
Other Name: AG-013736

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Locally advanced renal cell carcinoma without evidence of metastatic disease with absence of adjacent organ invasion or retroperitoneal adenopathy (cT2-T3b, N0, M0). Patients with retroperitoneal lymph nodes </= 2cm in size each are considered N0.
  2. Predominant clear cell histology on pre-treatment biopsy of the primary tumor.
  3. Patient should be candidate for curative radical nephrectomy.
  4. ECOG Performance Status 0-1.
  5. Patient must provide signed informed consent.
  6. Male or female, age >/= 18 years.
  7. Adequate renal function: serum creatinine level </=1.5 x ULN or calculated creatinine clearance (as estimated by GFR using the MDRD formula) is >/= 60 ml/min.
  8. Adequate hepatic function: alkaline phosphatase </= 1.5 x ULN; total bilirubin, AST, and ALT </= 1.5 x ULN; INR <1.3 (or <3 if on anticoagulant therapy).
  9. Adequate bone marrow function: ANC >/= 1.5 x 10/ 9L; Platelets >/= 100 x 109/L; Hb >9 g/dL
  10. Urinary protein <100 on urinalysis (equivalent to <2+ by urine dipstick). If urinalysis protein >/=100 (equivalent to dipstick is >/=2+) then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours
  11. No hormonal therapy, chemotherapy, immunotherapy, or any other systemic therapy for a malignancy, in the 5 years prior to current study enrollment.
  12. Women of childbearing potential (defined as a female subject who is not surgically sterilized, not at least 1 year postmenopausal) must have negative urine or serum pregnancy test within 4 weeks of enrollment and again on the day of starting therapy and she and/or her partner must utilize birth control while on therapy.
  13. Male (defined as a male subject who has not been surgically sterilized) or female patients of child-producing potential must agree to use adequate contraception (e.g. IUD, condom plus spermicide, diaphragm, or cervical cap plus spermicide) or medical contraception: as of date of study enrollment and for at least 1 month after last dose of axitinib. Subjects who are not currently sexually active must agree and consent to use one of the above-mentioned methods should they become sexually active while participating in the study.

Exclusion Criteria:

  1. Evidence of metastatic disease, adjacent organ invasion, retroperitoneal adenopathy on pre-treatment imaging. In addition, patients with inferior vena cava thrombi extending to the atrium or with evidence of Budd-Chiari Syndrome (hepatic dysfunction) will not be eligible for the protocol.
  2. Patients who undergo embolization of their primary tumor.
  3. Previous treatment for their primary renal tumor, including prior chemotherapy, immunotherapy, targeted therapy, radiation therapy, cryotherapy, radiofrequency ablation or embolization.
  4. Active malignancies other than renal cell carcinoma and/or history of other malignancy within the last 5 years, except for adequately treated cone-biopsied in situ carcinoma of the cervix or basal or squamous cell carcinoma of the skin
  5. Uncontrolled hypertension (BP>140/90 on medications), as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be </=140 mm Hg, and the baseline diastolic blood pressure readings must be </=90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
  6. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, nefazodone, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine).
  7. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort).
  8. Active gastrointestinal bleeding.
  9. Malabsorption syndromes such as celiac disease, cystic fibrosis, inflammatory bowel disease, systemic sclerosis, and carcinoid syndrome.
  10. Known HIV or Hepatitis C status.
  11. Requirement of anticoagulant therapy with oral vitamin K antagonists. 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.
  12. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
  13. A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
  14. 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
  15. Withdrawal of consent.
  16. Unwillingness or inability to comply with mandated pretreatment biopsy or therapeutic regimen.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01263769

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pfizer
Investigators
Principal Investigator: Christopher Wood, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01263769     History of Changes
Other Study ID Numbers: 2010-0072
Study First Received: December 17, 2010
Last Updated: December 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Locally advanced clear cell renal cell carcinoma
AG-013736
Axitinib
Radical nephrectomy

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 20, 2014