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

Alternate Title

Octreotide and Interferon alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active Not specified NCI SWOG-S0518 S0518, NCT00569127

Special Category: CTSU trial, NCI Web site featured trial

Objectives

1. To compare central review-based progression-free survival (PFS) in poor prognosis carcinoid patients treated with either depot octreotide acetate plus bevacizumab or depot octreotide acetate plus interferon.
2. To compare overall survival, time to treatment failure, and traditionally reported progression-free survival of poor prognosis carcinoid patients treated with either depot octreotide acetate plus bevacizumab or depot octreotide acetate plus interferon.
3. To compare objective response (confirmed and unconfirmed complete and partial response) in poor prognosis carcinoid patients treated with either depot octreotide acetate plus bevacizumab or depot octreotide acetate plus interferon.
4. To compare the toxicity profile of these two regimens in these patients.
5. To assess the prognostic and predictive value of VEGF expression in relation to PFS and treatment effect.
6. To compare response of 5HIAA, chromogranin A, and neurospecific enolase among patients with elevated levels at baseline between patients treated with octreotide acetate plus interferon versus octreotide acetate plus bevacizumab.
7. To assess and compare the prognostic and predictive value of the combination of IN-111 pentetreotide somatostatin-receptor scintigraphy (SRS) and CT scan vs. CT scan alone in relation to PFS.
8. To assess and compare the prognostic and predictive value of the combination of SRS and CT scan vs CT scan alone in relation to overall survival and time to treatment failure.

Entry Criteria

Disease Characteristics:

Inclusion criteria:

• Diagnosis of unresectable metastatic or locally advanced, low- or intermediate-grade neuroendocrine carcinoma, including the following subtypes:
  • Carcinoid tumor, low-grade or well differentiated neuroendocrine carcinoma
  • Atypical carcinoid tumor, intermediate-grade or moderately differentiated neuroendocrine carcinoma



• High-risk disease as defined by at least one of the following:
  • Progressive disease
  • Refractory carcinoid syndrome while receiving octreotide acetate (i.e., defined by > 2 flushing episodes/day or > 4 bowel movements/day)
  • Atypical histology and more than 6 lesions
  • Metastatic colorectal carcinoid tumor
    • Patients with metastatic cecal or appendiceal carcinoid tumor are not eligible unless they fit other mentioned high-risk features
  • Metastatic gastric carcinoid tumor



• Measurable disease



• Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid tumor, or goblet cell carcinoid tumor are not eligible

Exclusion criteria:

• Osseous metastasis as only site of disease



• Medullary thyroid carcinoma or islet cell carcinoma



• History of primary brain tumor or metastatic cancer to the brain

Prior/Concurrent Therapy:

• Recovered from all prior therapy
• At least 28 days since and no more than 1 prior regimen of cytotoxic chemotherapy
• At least 28 days since prior hepatic artery embolization provided there is residual measurable disease
  • Chemoembolization is considered as 1 prior chemotherapy regimen
• No prior interferon, bevacizumab, or any other therapy targeting VEGF or VEGF receptors (e.g., SU11248, PTK/ZK, sorafenib tosylate, or pazopanib hydrochloride)
• Prior therapy targeting c-kit, abl, PDGFR, mTOR, and somatostatin receptors allowed
• At least 28 days since prior radiotherapy
  • Target lesions must have show disease progression if therapy included peptide receptor radiotherapy
• At least 1 week since prior minor surgery
• At least 4 weeks since prior major surgery
• At least 21 days since prior octreotide acetate therapy
• Concurrent full-dose anticoagulation (warfarin or low molecular weight heparin) allowed provided the following criteria are met:
  • In-range INR (e.g., between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., varices)
• No concurrent interferon to control carcinoid syndrome for patients receiving bevacizumab
  • Other supportive care medication (e.g., short acting octreotide acetate) allowed
• No other concurrent chemotherapy, immunotherapy, radiotherapy, hepatic artery embolization, hepatic artery chemoembolization, radiofrequency ablation, or other tumor ablative procedure
• No other investigational or commercial agents

Patient Characteristics:

Inclusion criteria:

• Zubrod performance status 0-2
• Platelet count > 100,000/mm³
• ANC > 1,500/mm³
• Hemoglobin > 8 g/dL
• Serum bilirubin < 1.5 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 2.5 times ULN
• Serum creatinine < 1.5 mg/dL
• 24-hour urine protein < 1,000 mg if urine protein:creatinine ratio > 0.5
• PT and PTT ≤ 1.1 times ULN
• History of hypertension must be well controlled (i.e., blood pressure < 150/90 mm Hg) on a stable regimen of antihypertensive therapy
• Not pregnant or nursing
• Fertile patients must use effective barrier method contraception during and for 6 months after completion of study treatment

Exclusion criteria:

• History or evidence of clinically significant peripheral vascular disease (e.g., non-healing peripheral ulcers or claudication)
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• Bleeding diathesis or coagulopathy that results in spontaneous bleeding (in the absence of trauma) requiring red blood cell transfusion within the past 5 years
• Serious (i.e., requiring active medical therapy with medication or medical device under the supervision of a physician) non-healing wound, ulcer, or bone fracture
• Recent history (i.e., within the past 6 months) of any of the following arterial thromboembolic events:
  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina
  • Myocardial infarction
  • New York Heart Association class II or higher congestive heart failure
• Hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia
• Pregnant or nursing
• Any other prior malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer
• Any immunologically mediated disease, including any of the following:
  • Inflammatory bowel disease (Crohn disease, ulcerative colitis)
  • Rheumatoid arthritis
  • Idiopathic thrombocytopenia purpura
  • Systemic lupus erythematosus
  • Autoimmune hemolytic anemia
  • Scleroderma
  • Severe psoriasis
• Any serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this treatment
• Psychiatric disorders rendering patient incapable of complying with the requirements of the protocol

Expected Enrollment

Outcomes

Progression-free survival

Overall survival
Time to treatment failure
Progression-free survival (reported traditionally)
Objective response
Toxicity

Outline

This is a multicenter study. Patients are stratified according to site of disease (small bowel vs cecum vs appendix vs other site), disease progression after initial diagnosis (yes or no), histologic grade (low vs intermediate [atypical]), and prior octreotide acetate therapy within the past 2 months (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I (octreotide acetate and bevacizumab): Patients receive depot octreotide acetate intramuscularly (IM) and bevacizumab IV over 30-90 minutes on day 1.



• Arm II (octreotide acetate and interferon alfa-2b): Patients receive octreotide acetate IM as in arm I on day 1 and interferon alfa-2b subcutaneously (SC) on days 1, 3, 5, 8, 10, 12, 15, 17, and 19.

Treatment in both arms repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 2-6 months for up to 3 years.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

James Yao, MD, Protocol chair		Ph: 713-792-2828; 800-392-1611

U.S.A.
Alabama
	Mobile
	Providence Cancer Center at Providence Hospital
		Paul Schwarzenberger, MD	Ph:  251-435-5892
Arkansas
	Ft. Smith
	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
		John Wells, MD	Ph:  479-484-4700 800-333-1305
California
	Berkeley
	Alta Bates Summit Comprehensive Cancer Center
		Clinical Trials Office - Alta Bates Summit Comprehensive Cancer Center	Ph:  510-204-3428
	Burlingame
	Peninsula Medical Center
		David Irwin, MD	Ph:  510-204-2866
	Greenbrae
	Marin Cancer Institute at Marin General Hospital
		David Irwin, MD	Ph:  510-204-2866
	Sutter Health - Western Division Cancer Research Group
		David Irwin, MD	Ph:  510-204-2866
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	San Diego
	Kaiser Permanente Medical Office -Vandever Medical Office
		Han Koh	Ph:  619-528-2596
	San Francisco
	California Pacific Medical Center - California Campus
		David Irwin, MD	Ph:  510-204-2866
	Vallejo
	Sutter Solano Medical Center
		David Irwin, MD	Ph:  510-204-2866
Colorado
	Fort Collins
	Front Range Cancer Specialists
		Diana Medgyesy, MD	Ph:  970-212-7600
	Poudre Valley Hospital
		Clinical Trials Office - Poudre Valley Hospital	Ph:  970-495-8226
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Clinical Trials Office - Tunnell Cancer Center	Ph:  302-645-3171
	Newark
	CCOP - Christiana Care Health Services
		Clinical Trial Office - CCOP - Christiana Care Health Services	Ph:  302-733-6227
District of Columbia
	Washington
	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
		Clinical Trials Office - Lombardi Comprehensive Cancer Center	Ph:  202-444-0381
Georgia
	Gainesville
	Northeast Georgia Medical Center
		Charles Nash, MD	Ph:  770-535-3553
Illinois
	Alton
	Saint Anthony's Hospital at Saint Anthony's Health Center
		Bethany Sleckman, MD	Ph:  314-251-6573
	Aurora
	Rush-Copley Cancer Care Center
		Kendrith Rowland, MD	Ph:  217-383-3010
	Bloomington
	St. Joseph Medical Center
		John Kugler, MD	Ph:  309-243-3000
	Canton
	Graham Hospital
		John Kugler, MD	Ph:  309-243-3000
	Carthage
	Memorial Hospital
		John Kugler, MD	Ph:  309-243-3000
	Chicago
	Hematology and Oncology Associates
		Clinical Trails Office - Hematology and Oncology Associates	Ph:  312-695-1301
	Robert H. Lurie Comprehensive Cancer Center at Northwestern University
		Clinical Trials Office - Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Ph:  312-695-1301
			Email: cancer@northwestern.edu
	Decatur
	Decatur Memorial Hospital Cancer Care Institute
		Clinical Trials Office - Decatur Memorial Hospital Cancer Care Institute	Ph:  217-876-6601
	Effingham
	St. Anthony's Memorial Hospital
		Clinical Trials Office - St. Anthony's Memorial Hospital	Ph:  217-347-1305
	Eureka
	Eureka Community Hospital
		John Kugler, MD	Ph:  309-243-3000
	Galesburg
	Galesburg Clinic, PC
		John Kugler, MD	Ph:  309-243-3000
	Galesburg Cottage Hospital
		John Kugler, MD	Ph:  309-243-3000
	Havana
	Mason District Hospital
		John Kugler, MD	Ph:  309-243-3000
	Hopedale
	Hopedale Medical Complex
		John Kugler, MD	Ph:  309-243-3000
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Kendrith Rowland, MD	Ph:  217-383-3010
	Midwest Center for Hematology/Oncology
		Al Benson, MD, FACP	Ph:  815-740-1400
	La Grange
	La Grange Memorial Hospital
		Clinical Trials Office - La Grange Memorial Hospital	Ph:  630-856-7526
	Libertyville
	North Shore Oncology and Hematology Associates, Limited - Libertyville
		Al Benson, MD, FACP	Ph:  847-367-6781
	Macomb
	McDonough District Hospital
		John Kugler, MD	Ph:  309-243-3000
	Moline
		Costas Constantinou, MD
		Costas Constantinou, MD	Ph:  916-734-2781
		Costas Constantinou, MD	Ph:  309-779-4265
		Costas Constantinou, MD	Ph:  309-779-5090
	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
		Costas Constantinou, MD	Ph:  309-779-5092
	Mt. Vernon
	Good Samaritan Regional Health Center
		Bethany Sleckman, MD	Ph:  314-251-6573
	Niles
	Cancer Care and Hematology Specialists of Chicagoland - Niles
		Al Benson, MD, FACP	Ph:  847-827-9060
	Normal
	BroMenn Regional Medical Center
		John Kugler, MD	Ph:  309-243-3000
	Community Cancer Center
		John Kugler, MD	Ph:  309-243-3000
	Ottawa
	Community Hospital of Ottawa
		John Kugler, MD	Ph:  309-243-3000
	Oncology Hematology Associates of Central Illinois, PC - Ottawa
		John Kugler, MD	Ph:  309-243-3000
	Pekin
	Cancer Treatment Center at Pekin Hospital
		John Kugler, MD	Ph:  309-243-3000
	Peoria
	CCOP - Illinois Oncology Research Association
		John Kugler, MD	Ph:  309-243-3000
	Methodist Medical Center of Illinois
		Clinical Trials Office - Methodist Medical Center of Illinois	Ph:  309-243-3000
	Oncology Hematology Associates of Central Illinois, PC - Peoria
		John Kugler, MD	Ph:  309-243-3000
	OSF St. Francis Medical Center
		John Kugler, MD	Ph:  309-243-3000
	Proctor Hospital
		John Kugler, MD	Ph:  309-243-3000
	Peru
	Illinois Valley Community Hospital
		John Kugler, MD	Ph:  309-243-3000
	Princeton
	Perry Memorial Hospital
		John Kugler, MD	Ph:  309-243-3000
	Rockford
	Swedish-American Regional Cancer Center
		Clinical Trials Office - Swedish-American Regional Cancer Center	Ph:  815-489-4413
	Skokie
	Hematology Oncology Associates - Skokie
		Al Benson, MD, FACP	Ph:  847-568-9930
	Spring Valley
	St. Margaret's Hospital
		John Kugler, MD	Ph:  309-243-3000
	Springfield
	Regional Cancer Center at Memorial Medical Center
		Clinical Trials Office - Regional Cancer Center at Memorial Medical Center	Ph:  217-788-4233
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Clinical Trials Office - Carle Cancer Center	Ph:  800-446-5532
	CCOP - Carle Cancer Center
		Clinical Trials Office - CCOP - Carle Cancer Center	Ph:  800-446-5532
Indiana
	Michigan City
	Saint Anthony Memorial Health Centers
		Kendrith Rowland, MD	Ph:  217-383-3010
Iowa
	Ames
	McFarland Clinic, PC
		Clinical Trials Office - McFarland Clinic, PC	Ph:  515-239-2621
	Bettendorf
		Costas Constantinou, MD	Ph:  563-421-1960
	Hematology Oncology Associates of the Quad Cities
		Shobha Chitneni, MD, MBBS	Ph:  563-355-7733
	Davenport
	Genesis Medical Center - West Campus
		George Kovach, MD	Ph:  563-421-1960
	Genesis Regional Cancer Center at Genesis Medical Center
		George Kovach, MD	Ph:  563-421-1960
	Sioux City
	Mercy Medical Center - Sioux City
		Donald Wender, MD, PhD	Ph:  712-252-9326
	Siouxland Hematology-Oncology Associates, LLP
		Donald Wender, MD, PhD	Ph:  712-252-9326
	St. Luke's Regional Medical Center
		Donald Wender, MD, PhD	Ph:  712-252-9326
Kansas
	Chanute
	Cancer Center of Kansas, PA - Chanute
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Dodge City
	Cancer Center of Kansas, PA - Dodge City
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	El Dorado
	Cancer Center of Kansas, PA - El Dorado
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Kansas City
	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
		Clinical Trials Office - Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Ph:  913-588-4709
	Kingman
	Cancer Center of Kansas, PA - Kingman
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Liberal
	Southwest Medical Center
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Newton
	Cancer Center of Kansas, PA - Newton
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Olathe
	Olathe Cancer Center
		Karen Kelly, MD	Ph:  303-724-3903
	Parsons
	Cancer Center of Kansas, PA - Parsons
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Pratt
	Cancer Center of Kansas, PA - Pratt
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Salina
	Cancer Center of Kansas, PA - Salina
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Tammy Walker Cancer Center at Salina Regional Health Center
		William Cathcart-Rake, MD	Ph:  785-827-7261
	Wellington
	Cancer Center of Kansas, PA - Wellington
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Wichita
	Associates in Womens Health, PA - North Review
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Cancer Center of Kansas, PA - Wichita
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Cancer Center of Kansas, PA - Medical Arts Tower
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	CCOP - Wichita