Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC)

NCT01263769 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2010-0072NCI-2011-00279
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Cancer

Keywords

Locally advanced clear cell renal cell carcinoma; AG-013736; Axitinib; Radical nephrectomy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response rate is defined as Complete Response (CR)+ Partial Response (PR) and evaluated when CT abdomen is done after 12 weeks of treatment. Per Response Evaluation Criteria in Solid Tumors Criteria ( RECIST v1.0) Complete Response (CR) is complete disappearance of renal mass; and, Partial Response (PR) is \>= 30% decrease in the largest diameter (LD) of the renal mass taking as reference the baseline largest diameter.

  12 weeks

Secondary Outcomes (4)

• Recurrence Free Survival

  After completion of treatment, patients followed w/evaluations every 4 months for 1st year, then every 6 months for next 2 years, yearly until disease progression identified or start of new treatment & yearly survival thereafter until study completion

• Overall Survival

  From date of randomization until the date of death from any cause, or date of last follow-up, whichever came first, assessed up to 5 years

• Postoperative Complications-Any Grade

  From surgery until 30 days after surgery

• Surgery-related Complications - High Grade

  From surgery until 30 days after surgery

Study Arms (1)

Axitinib

EXPERIMENTAL

Axitinib Starting dose: 5 mg by mouth twice each day for 12 weeks.

Drug: Axitinib

Interventions

Axitinib DRUG

Starting dose: 5 mg by mouth twice each day for 12 weeks.

Also known as: AG-013736

Axitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Predominant clear cell histology on pre-treatment biopsy of the primary tumor.
• Patient should be candidate for curative radical nephrectomy.
• ECOG Performance Status 0-1.
• Patient must provide signed informed consent.
• Male or female, age \>/= 18 years.
• 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.
• 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).
• Adequate bone marrow function: ANC \>/= 1.5 x 10/ 9L; Platelets \>/= 100 x 109/L; Hb \>9 g/dL
• 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
• No hormonal therapy, chemotherapy, immunotherapy, or any other systemic therapy for a malignancy, in the 5 years prior to current study enrollment.
• 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.
• 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.

You may not qualify if:

• 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.
• Patients who undergo embolization of their primary tumor.
• Previous treatment for their primary renal tumor, including prior chemotherapy, immunotherapy, targeted therapy, radiation therapy, cryotherapy, radiofrequency ablation or embolization.
• 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
• 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.
• 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).
• 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).
• Active gastrointestinal bleeding.
• Malabsorption syndromes such as celiac disease, cystic fibrosis, inflammatory bowel disease, systemic sclerosis, and carcinoid syndrome.
• Known HIV or Hepatitis C status.
• 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.
• Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
• A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
• 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
• Withdrawal of consent.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Pfizer: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Karam JA, Devine CE, Urbauer DL, Lozano M, Maity T, Ahrar K, Tamboli P, Tannir NM, Wood CG. Phase 2 trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma. Eur Urol. 2014 Nov;66(5):874-80. doi: 10.1016/j.eururo.2014.01.035. Epub 2014 Feb 7.

  PMID: 24560330 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Kidney Neoplasms

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Jose Karam, MD, Associate Professor, Urology
• Organization: UT MD Anderson Cancer Center

jakaram@mdanderson.org

(713) 745-0374

Study Officials

• Jose Karam, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2010
• First Posted: December 21, 2010
• Study Start: February 1, 2011
• Primary Completion: February 1, 2021
• Study Completion: June 5, 2023
• Last Updated: September 19, 2024
• Results First Posted: February 3, 2022

Record last verified: 2024-08

Locations

US (1)