Active, not recruiting
Phase 3
Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor
Condition(s) studied
Colorectal Neuroendocrine Tumor G1Gastric Neuroendocrine Tumor G1Neuroendocrine NeoplasmNeuroendocrine TumorNeuroendocrine Tumor G2
Investigational drug(s) / intervention(s)
Bevacizumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Octreotide Acetate: Given IM
Recombinant Interferon Alfa-2b: Given SC
Study summary
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.
Eligibility
Inclusion Criteria:
* Patient must have unresectable metastatic or locally advanced, low- or intermediate-grade neuroendocrine carcinoma
* NOTE: pathology report must state one of the following: carcinoid, low-grade or well-differentiated neuroendocrine carcinoma, atypical carcinoid, intermediate-grade or moderately differentiated neuroendocrine carcinoma; patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, or goblet cell carcinoid are not eligible; patient must not have osseous metastasis as only site of disease; patients with medullary thyroid carcinoma or islet cell carcinoma are not eligible; if pathology report states only neuroendocrine carcinoma, pathology subtype must be reconfirmed
* Occasionally, it is not possible to establish tumor grade on fine-needle aspiration (FNA) cytology material; if a new biopsy is needed, a core needle biopsy should be obtained whenever possible
* Patient must have high risk disease as defined by at least one of the following:
* Progressive disease
* Refractory carcinoid syndrome while receiving octreotide (defined by \> 2 flushing episodes/day or \> 4 bowel movements/day)
* Atypical histology and more than 6 lesions
* Metastatic colorectal carcinoid; patients with metastatic cecal or appendiceal carcinoid tumor are not eligible unless the tumors fit into one of the other high-risk categories (a, b, or c above)
* Metastatic gastric carcinoid
* Patient must have measurable disease; CT or magnetic resonance imaging (MRI) used for tumor measurement must have been completed within 28 days prior to registration; X-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form; these scans also must be submitted for central radiology review
* Institutions are required to submit CT/MRI scans and archived tissue for pathology review; furthermore, institutions are required to seek additional patient consent for submission of octreotide scans, and submission of blood and use of archived tissue for correlative studies
* If patient consents to the submission of octreotide scans, the patient must also be registered to Registration Step 2
* Patient may have had up to one prior regimen of cytotoxic chemotherapy; at least 28 days must have elapsed since completion of prior therapy, and patient must have recovered from all effects
* Patient may have had prior hepatic artery embolization; at least 28 days must have elapsed since embolization and there must be residual measurable disease; chemoembolization will be considered as one prior chemotherapy regimen
* Patient must not have received prior interferon, bevacizumab or any other therapy targeting VEGF or VEGF receptors
* Patient may have received prior therapy targeting stem cell factor receptor (c-kit), abelson murine leukemia viral oncogene homolog 1 (abl), platelet-derived growth factor receptor (PDGFR), mammalian target of rapamycin (mTOR), and somatostatin receptors (not counted toward prior cytotoxic chemotherapy)
* Prior radiation is allowed; there must be measurable disease; if prior therapies include peptide receptor radiotherapy, the target lesion(s) must have shown disease progression; at least 28 days must have elapsed since completion of prior therapy, and patient must have recovered from all effects
* Patients must have recovered from any prior surgery; one week must have elapsed from the time of a minor surgery and 4 weeks from major surgery
* At least 21 days must have elapsed since any prior octreotide LAR depot treatment
* Patient must have a Zubrod performance status of 0-2
* Absolute neutrophil count (ANC) \> 1,500/mcl
* Hemoglobin \> 8 g/dl
* Platelets \> 100,000/mcl
* Serum bilirubin \< 1.5 x institutional upper limit of normal (IULN)
* Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x IULN
* Serum creatinine \< 1.5 mg/dL
* Urine protein must be screened by urine analysis for Urine Protein Creatinine (UPC) ratio; for UPC ratio \> 0.5, 24-hour urine protein must be obtained and the level must be \< 1,000 mg for patient enrollment; these results must be obtained within 28 days prior to registration
* Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
* Patients not on anticoagulation must have prothrombin time (PT) and partial thromboplastin time (PTT) =\< 1.1 x lULN obtained within 28 days prior to registration; patients on full-dose anticoagulation (warfarin or low molecular weight heparin) are eligible provided that both of the following criteria are met:
* The patient has an in-range international normalized ratio (INR) (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
* The patient has no active bleeding or pathological condition that carries a high risk of bleeding such as varices
* Patient must not have history or evidence of clinically significant peripheral vascular disease such as non-healing peripheral ulcers or claudication
* Patient must not have a history of primary brain tumor or metastatic cancer to the brain; brain imaging studies are not required for eligibility if the patient has no neurological signs or symptoms; if brain imaging studies are performed, they must be negative for disease
* Patient must not have a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration
* Patient must not have history within the past 5 years or presence of bleeding diathesis or coagulopathy that results in spontaneous bleeding (in the absence of trauma) requiring packed red blood cells (pRBC) transfusion
* Patient must not have a serious (requiring active medical therapy with medication or medical device under the supervision of a physician) non-healing wound, ulcer, or bone fracture
* Patient must not have recent history (within 6 months prior to registration) of these arterial thromboembolic events: transient ischemic attack, cerebrovascular accident, unstable angina, myocardial infarction, or New York Heart Association grade II or higher congestive heart failure
* Patients with a history of hypertension must be well-controlled (blood pressure \< 150/90), on a stable regimen of antihypertensive therapy
* Patient must not have hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia
* Patient must not plan to use any other concurrent chemotherapy, immunotherapy, hepatic artery embolization, hepatic artery chemoembolization, radiofrequency ablation, other tumor ablative procedure or radiotherapy while on protocol treatment
* Patient must not be pregnant or nursing because bevacizumab may be harmful to the developing fetus and newborn; male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout protocol treatment and for up to 6 months following discontinuation of bevacizumab
* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years
* All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
* At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional re view board approval for this study has been entered into the data base
* REGISTRATION STEP 2 - SPECT SUBSTUDY
* Patient must have registered to the main study
* Patient must have consented to the submission of octreotide scans
* An octreotide scan obtained within 28 days prior to Registration Step 1 must be available for submission
Primary outcome measure(s)
- Central Review-based Progression-Free Survival — Up to 3 years
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.
Trial sites (493)
| Facility | City | Region | Status |
| Providence Hospital |
Mobile |
Alabama |
|
| Fairbanks Memorial Hospital |
Fairbanks |
Alaska |
|
| Mercy Hospital Fort Smith |
Fort Smith |
Arkansas |
|
| NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro |
Jonesboro |
Arkansas |
|
| University of Arkansas for Medical Sciences |
Little Rock |
Arkansas |
|
| Highlands Oncology Group - Rogers |
Rogers |
Arkansas |
|
| Kaiser Permanente-Anaheim |
Anaheim |
California |
|
| Arroyo Grande Community |
Arroyo Grande |
California |
|
| PCR Oncology |
Arroyo Grande |
California |
|
| Kaiser Permanente-Baldwin Park |
Baldwin Park |
California |
|
| Kaiser Permanente-Bellflower |
Bellflower |
California |
|
| Alta Bates Summit Medical Center-Herrick Campus |
Berkeley |
California |
|
| Providence Saint Joseph Medical Center/Disney Family Cancer Center |
Burbank |
California |
|
| Mills-Peninsula Medical Center |
Burlingame |
California |
|
| Kaiser Permanente-Fontana |
Fontana |
California |
|
| Marin General Hospital |
Greenbrae |
California |
|
| Kaiser Permanente South Bay |
Harbor City |
California |
|
| Kaiser Permanente-Irvine |
Irvine |
California |
|
| Kaiser Permanente Los Angeles Medical Center |
Los Angeles |
California |
|
| Los Angeles General Medical Center |
Los Angeles |
California |
|
| USC / Norris Comprehensive Cancer Center |
Los Angeles |
California |
|
| Kaiser Permanente West Los Angeles |
Los Angeles |
California |
|
| Cedars-Sinai Medical Center |
Los Angeles |
California |
|
| Sutter Cancer Research Consortium |
Novato |
California |
|
| Stanford Cancer Institute Palo Alto |
Palo Alto |
California |
|
| Kaiser Permanente - Panorama City |
Panorama City |
California |
|
| Kaiser Permanente-Riverside |
Riverside |
California |
|
| Kaiser Permanente-Rio San Diego |
San Diego |
California |
|
| Kaiser Permanente-San Diego Zion |
San Diego |
California |
|
| California Pacific Medical Center-Pacific Campus |
San Francisco |
California |
|
| Kaiser Permanente-San Marcos |
San Marcos |
California |
|
| Sutter Pacific Medical Foundation |
Santa Rosa |
California |
|
| Sutter Solano Medical Center/Cancer Center |
Vallejo |
California |
|
| Kaiser Permanente-Woodland Hills |
Woodland Hills |
California |
|
| San Luis Valley Regional Medical Center |
Alamosa |
Colorado |
|
| The Medical Center of Aurora |
Aurora |
Colorado |
|
| Rocky Mountain Regional VA Medical Center |
Aurora |
Colorado |
|
| UCHealth University of Colorado Hospital |
Aurora |
Colorado |
|
| Boulder Community Foothills Hospital |
Boulder |
Colorado |
|
| Penrose-Saint Francis Healthcare |
Colorado Springs |
Colorado |
|
+ 453 more sites — see the full list on the official registry below.
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