Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Carcinoid Tumor

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

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Antibodies, Monoclonal

Bevacizumab

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Immunoglobulins, Intravenous

Octreotide

Interferon-alpha

Interferon alpha-2

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Antiviral Agents

Antineoplastic Agents, Hormonal

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.

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.

Laboratory Biomarker Analysis

Octreotide Acetate

Recombinant Interferon Alfa-2b

James C Yao

This randomized phase III trial studies octreotide acetate and recombinant interferon alfa-2b to see how well it works compared to octreotide acetate and bevacizumab in treating patients with high-risk neuroendocrine tumors that have spread to other places in the body (metastatic) or spread from where it started to nearby tissue or lymph nodes (locally advanced). 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, may interfere with the ability of tumor cells to grow and spread. 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).

SECONDARY OBJECTIVES:

I. 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.

II. To compare objective response (confirmed and unconfirmed complete response \[CR\] and partial response \[PR\]) in poor prognosis carcinoid patients treated with either depot octreotide plus bevacizumab, or depot octreotide plus interferon.

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

TERTIARY OBJECTIVES:

I. To assess the prognostic and predictive value of vascular endothelial growth factor (VEGF) expression in relation to progression-free survival and treatment effect.

II. 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.

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

IV. 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: Patients are randomized to 1 of 2 treatment arms.

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

ARM II: Patients receive octreotide acetate IM 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 up every 2-6 months for up to 3 years.

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

From date of randomization (which is the date of registration) to date of first documentation of progression based on Central Radiological Review of the appropriate CT or MRI scans, or symptomatic deterioration (as defined in Section 10.2e)), or development of new lesions or disease not identified on CT or MRI, or death due to any cause. Patients who have a local assessment of progression based on imaging, but for whom central review does not concur, will be censored at the last Central Radiological Review date, unless subsequent scans or documentation of symptomatic deterioration provides evidence of progression. Patients last known not to have progressed are censored at the date of last contact. Patients with incomplete Central Radiological Review are censored at the date of last Central Radiological Review if patient has not progressed prior to that time.

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

From date of randomization (which is the date of registration) to date of first observation of progressive disease (as defined in Section 10.2d), death due to any cause, symptomatic deterioration (as defined in Section 10.2e), or discontinuation of treatment. This has been calculated using Central-Review based progression events. Patients last known not to have failed treatment are censored at date last known not to have failed. Patients with incomplete Central Radiological Review are censored at the date of last Central Radiological Review if patient has not failed treatment prior to that time.

From date of randomization (which is the date of registration) to date of first documentation of progression \[per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as defined in Section 10.2d\] or symptomatic deterioration (as defined in Section 10.2e), or death due to any cause. Patients last known not to have progressed are censored at date of last contact. Progression (Section 10.2d) includes one or more of the following: 20% increase in the sum of the longest diameters of target measurable lesions over smallest sum observed using the same techniques as baseline; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of new lesion/site; or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration (Section 10.2e) is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.

Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0): Complete Response (CR) is disappearance of all measurable and non-measurable disease, and no new lesions; Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Confirmed response is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

Only adverse events that are possibly, probably or definitely related to study drug are reported.

National Cancer Institute (NCI)

Eligible patients who received treatment and were assessed for adverse events are included in the adverse event summaries. Eleven patients did not start protocol treatment due to: patient refusal (6), financial reasons (3), and worsening condition/progression (2). None were assessable for adverse events and thus are not included in this analysis.

Patients receive 20 mg depot octreotide acetate IM and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Octreotide, Bevacizumab

Patients receive 20 mg depot octreotide acetate IM on day 1 and 5 million units interferon alpha-2b three times per week (Days 1, 3, 5, 8, 10, 12, 15, 17, 19 of each cycle). Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Octreotide, Interferon Alpha-2b

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Small bowel, cecum, appendix

Other sites

Disease Site

Progression after Initial Diagnosis

Intermediate (atypical)

Histologic Grade

Within 2 months prior to registration

None within 2 months prior to registration

Prior Octreotide

SWOG Statistician

According to the intent-to-treat principle, all eligible patients will be included in this analysis according to the randomized treatment assignment, regardless of actual treatments received.

Overall Survival

According to the intent-to-treat principle, all eligible patients were included in the analysis according to the randomized treatment assignment, regardless of actual treatments received.

Central Review-based Progression-Free Survival

Time to Treatment Failure

Local Progression-Free Survival (Investigator Assessed)

Complete Response

Partial Response

Unconfirmed Complete Response

Unconfirmed Partial Response

Stable/No Resposne

Increasing Disease

Symptomatic Deterioration

Assessment Inadequate

All eligible patients with measurable disease will be included in this analysis according to the randomized treatment assignment.

Objective Response (Confirmed and Unconfirmed Complete Response and Partial Response)

ALT, SGPT (serum glutamic pyruvic transaminase)

AST, SGOT

Albumin, serum-low (hypoalbuminemia)

Alkaline phosphatase

Allergic reaction/hypersensitivity

Anorexia

Ataxia (incoordination)

Auditory/Ear-Other (Specify)

Bilirubin (hyperbilirubinemia)

CNS cerebrovascular ischemia

Cardiac troponin I (cTnI)

Cardiac-ischemia/infarction

Cardiopulmonary arrest, cause unknown (non-fatal)

Cholecystitis

Cognitive disturbance

Colitis

Constipation

Creatinine

Dehydration

Dental: periodontal disease

Diarrhea

Dizziness

Dyspnea (shortness of breath)

Edema: limb

Fatigue (asthenia, lethargy, malaise)

Fever in absence of neutropenia, ANC lt1.0x10e9/L

Fistula, GI - Colon/cecum/appendix

Fistula, GU - Vagina

Glucose, serum-high (hyperglycemia)

Hearing: pts w/o audiogram not enroll monitor prgm

Heartburn/dyspepsia

Hemoglobin

Hemorrhage, CNS

Hemorrhage, GI - Rectum

Hemorrhage, GI - Upper GI NOS

Hemorrhage, pulmonary/upper respiratory - Nose

Hemorrhage/Bleeding-Other (Specify)

Hot flashes/flushes

Hydrocephalus

Hypertension

Hypotension

Hypoxia

INR (of prothrombin time)

Ileus, GI (functional obstruction of bowel)

Inf (clin/microbio) w/Gr 3-4 neuts - Blood

Inf (clin/microbio) w/Gr 3-4 neuts - Lung

Inf (clin/microbio) w/Gr 3-4 neuts - Nose

Inf w/normal ANC or Gr 1-2 neutrophils - Ab NOS

Inf w/normal ANC or Gr 1-2 neutrophils - Lung

Inf w/normal ANC or Gr 1-2 neutrophils - UTI

Infection with unknown ANC - Scrotum

Infection with unknown ANC - Urinary tract NOS

Insomnia

Left ventricular systolic dysfunction

Leukocytes (total WBC)

Lipase

Lymphopenia

Mental status

Mood alteration - agitation

Mood alteration - anxiety

Mood alteration - depression

Mucositis/stomatitis (clinical exam) - Oral cavity

Mucositis/stomatitis (functional/symp) - Oral cav

Muscle weakness, not d/t neuropathy - body/general

Nausea

Neuropathy: motor

Neutrophils/granulocytes (ANC/AGC)

Obstruction, GI - Gallbladder

Obstruction, GI - Small bowel NOS

Pain - Abdomen NOS

Pain - Back

Pain - Bone

Pain - Chest wall

Pain - Chest/thorax NOS

Pain - Esophagus

Pain - Extremity-limb

Pain - Gallbladder

Pain - Head/headache

Pain - Liver

Pain - Muscle

Pain - Stomach

Pain-Other (Specify)

Phosphate, serum-low (hypophosphatemia)

Platelets

Pneumonitis/pulmonary infiltrates

Potassium, serum-low (hypokalemia)

Proteinuria

Pruritus/itching

Rash/desquamation

Renal failure

Renal/Genitourinary-Other (Specify)

Seizure

Sodium, serum-low (hyponatremia)

Somnolence/depressed level of consciousness

Syncope (fainting)

Thrombosis/embolism (vascular access-related)

Thrombosis/thrombus/embolism

Triglyceride, serum-high (hypertriglyceridemia)

Ulcer, GI - Duodenum

Ulcer, GI - Stomach

Eligible patients who received any treatment and were assessed for adverse events are included in this summary. Eleven patients did not start protocol treatment due to: patient refusal (6), financial reasons (3), and worsening condition/progression (2). None were assessable for adverse events and thus are not included in this analysis.

Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor	NCT00569127	Colorectal Neur... Gastric Neuroen... Neuroendocrine ... Neuroendocrine ... Neuroendocrine ...	Bevacizumab Laboratory Biom... Octreotide Acet... Recombinant Int...	-	National Cancer Institute (NCI)
Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor	NCT00569127	Colorectal Neur... Gastric Neuroen... Neuroendocrine ... Neuroendocrine ... Neuroendocrine ...	Bevacizumab Laboratory Biom... Octreotide Acet... Recombinant Int...	-	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for gastric neuroendocrine tumor g1