Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

AG-013736 as Second-Line Therapy in Treating Patients With Metastatic Renal Cell (Kidney) Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	MSKCC-03117 PFIZER-A4061012, NCT00077272

Objectives

Primary

1. Determine the activity of AG-013736 as second-line treatment, in terms of overall objective response rate, complete response, and partial response, in patients with metastatic renal cell cancer.

Secondary

1. Determine the safety profile of this drug in these patients.
2. Determine the time to progression in patients treated with this drug.
3. Determine the duration of response in patients treated with this drug.
4. Determine the overall survival of patients treated with this drug.
5. Determine the effects of this drug on health-related quality of life in these patients.
6. Correlate the pharmacokinetics of this drug with response or adverse events in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed renal cell cancer
  • Metastatic disease
  • Unresected primary tumors allowed provided there is evidence of metastatic disease



• Failed 1 prior cytokine-based therapy (interleukin-2 and/or interferon alfa) due to disease progression or unacceptable treatment-related toxicity



• At least one unidimensionally measurable target lesion at least 2 cm (1 cm allowed for spiral CT scan)
  • Not in a previously irradiated field*
   [Note: *New lesions that have developed in a previously irradiated field are considered measurable]



• No evidence of brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• No prior antiangiogenesis agents, including thalidomide

Chemotherapy

• No concurrent chemotherapy for the primary disease

Endocrine therapy

• No concurrent hormonal therapy for the primary disease
• No concurrent dexamethasone

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy

Surgery

• More than 4 weeks since prior major surgery
• No prior surgical procedures affecting absorption (including gastric resection)

Other

• No other prior systemic treatment for renal cell cancer
• More than 6 months since prior treatment for active peptic ulcer disease
• No other concurrent experimental medications for the primary disease
• No other concurrent anticancer therapy
• No concurrent chronic antacid therapy with histamine H₂ antagonists or proton pump inhibitors
  • Concurrent locally acting antacids (e.g., Mylanta®, Maalox®, or Amphojel®) for acute control of gastric acid allowed provided the antacids are not administered 2 hours before, during, and 2 hours after study drug administration
• No concurrent drugs that are known potent CYP3A4 inhibitors, including any of the following:
  • Grapefruit juice
  • Verapamil
  • Ketoconazole
  • Miconazole
  • Itraconazole
  • Erythromycin
  • Clarithromycin
  • Indinavir
  • Saquinavir
  • Ritonavir
  • Nelfinavir
  • Lopinavir
  • Delavirdine
• No concurrent drugs that are known CYP3A4 or CYP1A2 inducers, including any of the following:
  • Carbamazepine
  • Felbamate
  • Omeprazole
  • Phenobarbital
  • Phenytoin
  • Primidone
  • Rifabutin
  • Rifampin
  • Hypericum perforatum (St. John's wort)

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• AST and ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• Bilirubin no greater than 1.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

  OR

• Creatinine clearance at least 60 mL/min
• Urinary protein less than 2+ by urine dipstick

  OR

• Urinary protein less than 2 g/24-hour urine collection

Cardiovascular

• No evidence of preexisting uncontrolled hypertension
  • Baseline systolic blood pressure no greater than 140 mm Hg and baseline diastolic blood pressure no greater than 90 mm Hg

Gastrointestinal

• Able to take oral medication
• No requirement for IV alimentation
• No active gastrointestinal bleeding unrelated to cancer (e.g., hematemesis, hematochezia, or melena) within the past 3 months unless there is resolution documented by endoscopy or colonoscopy
• No malabsorption syndromes

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• No active seizure disorder
• No other serious uncontrolled medical disorders
• No active infection
• No dementia or significantly altered mental status that would preclude giving informed consent or complying with study
• No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the breast or cervix.

Expected Enrollment

A total of 30-52 patients will be accrued for this study within 1 year.

Outline

This is an open-label, multicenter study.

Patients receive oral AG-013736 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline; at days 29 and 57 during therapy; every 8 weeks during therapy; at days 30 and 45 post-therapy; and then every 3 months for at least 1 year after the first dose of study drug.

Patients are followed at days 30 and 45 and then every 3 months for up to 2 years.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Robert Motzer, MD, Protocol chair		Ph: 646-422-4312; 800-525-2225

Registry Information
Official Title		Phase 2 Study Of AG-013736 As Second-Line Treatment In Patients With Metastatic Renal Cell Cancer
Registered in ClinicalTrials.gov		NCT00077272
Date Submitted to PDQ		2003-12-16
Information Last Verified		2005-04-06
NCI Grant/Contract Number		P30-CA08748

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