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

Alternate Title

SU011248 in Treating Patients With Metastatic Colorectal Adenocarcinoma (Cancer) That Has Not Responded to Previous Treatment With Irinotecan, Oxaliplatin, and a Fluoropyrimidine With or Without Bevacizumab

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	MSKCC-03143 PFIZER-A6181003, PFIZER-PHA-RTKC-0511, NCT00082771

Objectives

Primary

1. Determine the antitumor efficacy of SU011248 in patients with metastatic colorectal adenocarcinoma who failed prior treatment with irinotecan, oxaliplatin, and a fluoropyrimidine with or without bevacizumab.

Secondary

1. Determine the onset and duration of tumor control and 1-year survival rate in patients treated with this drug.
2. Determine the safety of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed colorectal adenocarcinoma not amenable to surgery, radiotherapy, or combined modality therapy with curative intent



• Must have received prior irinotecan, oxaliplatin, and a fluoropyrimidine in the adjuvant and/or advanced disease setting with or without bevacizumab (in the advanced disease setting) AND developed resistance to these prior therapies, as defined by one of the following:
  • Irinotecan-, oxaliplatin-, or fluoropyrimidine-resistant disease, defined as relapse or progression during treatment OR within 6 months after completing the most recent regimen
  • Bevacizumab-resistant disease, defined as disease progression during treatment OR within 6 months after completing bevacizumab



• At least one unidimensionally measurable lesion at least 20 mm by conventional radiographic techniques or MRI OR at least 10-16 mm by spiral CT scan
  • The following lesions are not considered measurable:
    • Bone lesions
    • Ascites
    • Peritoneal carcinomatosis or miliary lesions
    • Pleural or pericardial effusions
    • Lymphangitis of the skin or lung
    • Cystic lesions
    • Irradiated lesions
    • Disease documented by indirect evidence only (e.g., by laboratory test, such as alkaline phosphatase)



• No known brain or leptomeningeal disease

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• At least 3 weeks since prior immunotherapy and recovered
• No prior vascular endothelial growth factor inhibitors (except bevacizumab)
• No concurrent biological response modifiers
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy
• No more than 3 prior systemic chemotherapy-based regimens for advanced disease
• Prior chemoembolization therapy allowed provided areas of measurable disease are not affected
• No concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered
  • Areas of measurable disease must not be affected
• No concurrent radiotherapy to the sole site(s) of measurable disease
  • Concurrent palliative radiotherapy allowed provided the measurable lesions (study target lesions) are not included in the irradiated field

Surgery

• Recovered from prior surgery
• Prior surgery allowed provided areas of measurable disease are not affected
• More than 12 months since prior coronary/peripheral artery bypass graft
• No concurrent surgery in the sole site(s) of measurable disease

Other

• Prior intrahepatic therapy or cryotherapy allowed provided areas of measurable disease are not affected
• No prior tyrosine kinase inhibitors (except bevacizumab)
• No other concurrent anticancer treatment
• No other concurrent investigational drugs
• No concurrent participation in another clinical trial

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if abnormalities are due to underlying malignancy)
• Albumin ≥ 3.0 g/dL
• Bilirubin ≤ 1.5 times ULN
• PT and PTT ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• LVEF above lower limit of normal by MUGA
• No ongoing cardiac dysrhythmias ≥ grade 2
• No atrial fibrillation of any grade
• No prolongation of the QTc interval to > 450 msec (for males) or > 470 msec (for females)
• None of the following conditions within the past 12 months:
  • Myocardial infarction
  • Severe/unstable angina
  • Symptomatic congestive heart failure
  • Cerebrovascular accident
  • Transient ischemic attack
  • Deep vein thrombosis
  • Other thromboembolic event

Pulmonary

• No pulmonary embolism within the past 12 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Amylase and lipase ≤ ULN
• Adrenocorticotrophic hormone stimulation test normal
• No known HIV infection
• No AIDS-related illness
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

Expected Enrollment

A total of 76-126 patients (38-63 per stratum) will be accrued for this study.

Outline

This is an open-label, multicenter study. Patients are stratified according to prior bevacizumab (yes vs no).

Patients receive oral SU011248 once daily on days 1-28. Courses repeat every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days and then every 2 months for 1 year.

Saltz LB, Rosen LS, Marshall JL, et al.: Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. J Clin Oncol 25 (30): 4793-9, 2007.[PUBMED Abstract]

Lenz H, Marshall J, Rosen L, et al.: Phase II trial of SU11248 in patients with metastatic colorectal cancer (MCRC) after failure of standard chemotherapy. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-241, 2006.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Leonard Saltz, MD, Protocol chair		Ph: 212-639-2501; 800-525-2225

Registry Information
Official Title		A Phase II Study Of SU011248 In Patients With Metastatic Colorectal Cancer Who Have Previously Failed Treatment With Irinotecan, Oxaliplatin, And Fluoropyrimidine, With And Without Bevacizumab
Trial Start Date		2004-01-13
Registered in ClinicalTrials.gov		NCT00082771
Date Submitted to PDQ		2004-03-01
Information Last Verified		2005-04-06
NCI Grant/Contract Number		P30-CA08748

Back to Top