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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Kidney Cancer

Thank you

Trial Information

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


The Study Drug:

Axitinib is designed to decrease blood supply to the tumor, which may slow tumor growth.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take axitinib by mouth
2 times a day every day for 12 weeks. The dose may be changed based on any side effects you
may have. You should take the drug about 12 hours apart. You should take the pills at about
the same time each day. If you vomit anytime after taking a dose, you must not "make it up"
with an extra dose, but instead take the next dose as previously scheduled. Any missed dose
may be taken late up to 3 hours before the next scheduled dose, otherwise, it should be
skipped.

A blood pressure monitor will be given to each participant for home use. You will be given
instructions and shown how to monitor your blood pressure.

You will be provided with a calendar to record the date and time of each dose, and your
blood pressure reading before taking the drug. Missed doses should also be recorded. You
must also bring the study drug bottle to each study visit so the research nurse can count
any remaining pills.

A drug list will be given to you to record drugs taken within 4 weeks before you enrolled on
the study and while on study. A new list will be provided during each clinic visit. You
should not start a new prescription or over-the-counter drug before talking with the study
doctor, except in the case of a medical emergency.

Study Visits:

At Week 1:

- You will be asked about any drugs you may be taking.

- Your performance status will be recorded.

- You will complete the questionnaire about kidney cancer care. This questionnaire will
take about 5 minutes to complete.

- Women who are able to become pregnant will have a blood (about 1 teaspoon) or urine
pregnancy test.

At Week 3:

- Your medical history will be recorded.

- You will have a physical exam.

- Your performance status will be recorded.

- You will have an ECG.

- Blood (about 2 tablespoons) will be drawn for routine testing to check your thyroid
function.

- Urine (about 2 tablespoons) will be collected for routine testing.

- You will complete the questionnaire about kidney cancer care.

At Weeks 5 and 9, you will be called and asked if you have had any side effects. This call
should take about 10 minutes.

At Weeks 7 and 12:

- Your medical history will be recorded.

- You will have a physical exam.

- Your performance status will be recorded.

- Blood (about 2 tablespoons) will be drawn for routine testing and to check your thyroid
function.

- Urine (about 2 tablespoons) will be collected for routine testing.

- You will complete the questionnaire about kidney cancer care.

- You will have a CT scan of chest and abdomen to check the status of the disease.

- At Week 12 only, you will have an ECG.

At Week 13, you will have surgery to remove the kidney tumor. You will receive a separate
consent form for this surgery.

At Week 19:

- Your medical history will be recorded.

- You will have a physical exam.

- Your performance status will be recorded.

- Blood (about 2 tablespoons) will be drawn for routine testing and to check your thyroid
function.

- You will complete the questionnaire about kidney cancer care.

- You will have a CT scan of chest and abdomen to check the status of the disease.

- If you have been treated for high blood pressure while taking the drug, your blood
pressure will be monitored and your blood pressure medication will be reduced. Once
your blood pressure reaches a certain level, this will be managed by your primary care
doctor.

After Week 19, every 4 months (+/- 2 weeks) for the first 1 year, every 6 months (+/- 2
weeks) for the third and fourth year, then every year (+/- 1 month) for a total of 5 years
post surgery:

- Your medical history will be recorded.

- You will have a physical exam.

- Your performance status will be recorded.

- You will have a CT scan of the chest and abdomen to check the status of the disease.

- Blood (about 2 tablespoons) will be drawn for routine testing and to check your thyroid
function.

- You will complete the questionnaire about kidney cancer care (only during the first 2
years).

Length of Study:

You will take axitinib for up to 12 weeks. You will stop taking axitinib earlier than
expected if the disease gets worse or if you have severe side effects. In both cases, you
will move on to surgery after axitinib has been stopped.

After surgery, you will be contacted by the study staff every 4 months (+/- 2 weeks) for 1
year, every 6 months (+/- 2 weeks) for the next 2 years and every 12 months (+/- 1 month)
for 2 more years (for a total of 5 years after surgery).

This is an investigational study. Axitinib is FDA approved and commercially available to
treat advanced kidney cancer in adults when 1 previous drug treatment for this disease has
not worked. In this study, it is being used for research purposes.

Up to 24 patients are expected to receive the study medication, with total
enrollment/screening of up to 40 patients. All will be enrolled at MD Anderson.


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
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 clearance (as estimated by GFR using the MDRD formula) is >/= 60 ml/min.

8. Adequate hepatic function: alkaline phosphatase and ALT
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 readings must be 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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Objective Response Rate

Outcome Description:

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.

Outcome Time Frame:

12 weeks

Safety Issue:

No

Principal Investigator

Christopher Wood, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2010-0072

NCT ID:

NCT01263769

Start Date:

February 2011

Completion Date:

Related Keywords:

  • Kidney Cancer
  • Locally advanced clear cell renal cell carcinoma
  • AG-013736
  • Axitinib
  • Radical nephrectomy
  • Carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030