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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00569127
First received: December 5, 2007
Last updated: September 16, 2014
Last verified: September 2014

December 5, 2007
September 16, 2014
December 2007
January 2015   (final data collection date for primary outcome measure)
Central-review based progression-free survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
Analyzed using the stratified log rank test (which is the score test from the stratified Cox-model).
Progression-free survival
Complete list of historical versions of study NCT00569127 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Analyzed using the stratified log rank test (which is the score test from the stratified Cox-model).
  • Time to treatment failure [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Traditionally reported progression-free survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Objective response in patients with measurable disease [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Analyzed using a logistic regression model.
  • Adverse events, graded according to the NCI CTCAE version 3.0 for routine toxicity and version 4.0 for serious adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Overall survival
  • Time to treatment failure
  • Progression-free survival (reported traditionally)
  • Objective response
  • Toxicity
Not Provided
Not Provided
 
Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor
Phase III Prospective Randomized Comparison of Depot Octreotide Plus Interferon Alpha Versus Depot Octreotide Plus Bevacizumab (NSC #704865) in Advanced, Poor Prognosis Carcinoid Patients

This randomized phase III trial is studying giving octreotide acetate together with recombinant interferon alfa-2b to see how well it works compared with giving octreotide acetate together with bevacizumab in treating patients with metastatic or locally advanced, high-risk neuroendocrine tumor. Octreotide acetate and recombinant interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving octreotide acetate together with recombinant interferon alfa-2b is more effective than giving octreotide acetate together with bevacizumab in treating patients with neuroendocrine tumor.

PRIMARY OBJECTIVES:

I. To compare central review-based progression-free survival in poor prognosis carcinoid patients treated with either depot octreotide (octreotide acetate) plus bevacizumab, or depot octreotide plus interferon (recombinant interferon alfa-2b).

II. To compare overall survival, time to treatment failure and traditionally reported progression-free survival in poor prognosis carcinoid patients treated with either depot octreotide plus bevacizumab, or depot octreotide plus interferon.

III. To compare objective response (confirmed and unconfirmed CR and PR) in poor prognosis carcinoid patients treated with either depot octreotide plus bevacizumab, or depot octreotide plus interferon.

IV. To compare the toxicity profile of patients treated with these two regimens.

V. To assess the prognostic and predictive value of VEGF expression in relation to progression-free survival and treatment effect.

VI. To compare response of 5HIAA, chromogranin A and neuronspecific enolase among patients with elevated levels at baseline between patients treated with octreotide plus interferon versus octreotide plus bevacizumab.

VII. To assess and compare the prognostic and predictive value of the combination of In-111 pentetreotide somatostatin-receptor scintigraphy (SRS) and CT vs. CT in relation to progression-free survival (PFS).

VIII. To assess and compare the prognostic and predictive value of the combination of SRS and CT vs. CT in relation to overall survival (OS) and time to treatment failure (TTF).

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

ARM II: Patients receive octreotide acetate IM as in arm I on day 1 and recombinant 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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Neuroendocrine Carcinoma
  • Biological: recombinant interferon alfa-2b
    Given SC
    Other Names:
    • Alfatronol
    • Glucoferon
    • Heberon Alfa
    • IFN alpha-2B
    • Intron A
  • Drug: octreotide acetate
    Given IM
    Other Names:
    • Longastatin
    • Longastatina
    • Samilstin
    • SMS 201-995
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Experimental: Arm I (octreotide acetate and bevacizumab)
    Patients receive depot octreotide acetate IM and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: octreotide acetate
    • Biological: bevacizumab
  • Experimental: Arm II (octreotide acetate and recombinant interferon alfa-2b)
    Patients receive octreotide acetate IM as in arm I on day 1 and recombinant interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: recombinant interferon alfa-2b
    • Drug: octreotide acetate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
400
Not Provided
January 2015   (final data collection date for primary outcome measure)

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
  • 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
  • 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
  • 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
  • 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 shown 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
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00569127
NCI-2009-00778, NCI-2009-00778, CDR0000579151, SWOG-S0518, S0518, S0518, U10CA032102
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: James Yao Southwest Oncology Group
National Cancer Institute (NCI)
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP