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

Learn more about:
Related Clinical Trial
Bronchoscopic Laser Ablation of Peripheral Lung Tumors Physical Activity Intervention Before and After Surgery in Older Adults With Lung Cancer and Their Family Caregivers Personalized PRRT of Neuroendocrine Tumors Clinical and Pathologic Studies in Neuroendocrine Tumors Nivolumab With Ipilimumab in Subjects With Neuroendocrine Tumors Study of Pasireotide Long Acting Release (LAR) in Patients With Metastatic Neuroendocrine Tumors (NETs) Active Surveillance in Early Lung Cancer Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor Quarfloxin in Patients With Low to Intermediate Grade Neuroendocrine Carcinoma 68Ga-Dotatoc Positron Emission Tomography (PET) for Somatostatin Receptor-Positive Neuroendocrine Tumors (NETs) Nintedanib in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors Effect of Oral 5-HTP Intake on Urinary 5-HIAA Excretion Carcinoid Heart Disease and Peptide Receptor Radiotargetted Therapy Study of Pasireotide Long Acting Release (LAR) Injection in Patients With Acromegaly and Patients With Carcinoid Disease Cabozantinib and Nivolumab for Carcinoid Tumors Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors A Combination Study to Determine the Safety and Efficacy of Panzem NCD With Avastin in Metastatic Carcinoid Tumors A Study of Sunitinib Versus Placebo in Combination With Lanreotide in Patients With Progressive Advanced/Metastatic Midgut Carcinoid Tumors Endoscopic Treatment of Bronchial Carcinoid Tumors Study Evaluating SOM230 in Patients With Metastatic Carcinoid Tumors A Study of Axitinib in Advanced Carcinoid Tumors A Phase II Study of Ramucirumab With Somatostatin Analog Therapy in Patients With Advanced, Progressive Carcinoid Tumors

Brief Title

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

Official Title

Phase III Prospective Randomized Comparison of Depot Octreotide Plus Interferon Alpha Versus Depot Octreotide Plus Bevacizumab (NSC #704865) in Advanced, Poor Prognosis Carcinoid Patients

Brief 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.
    

Detailed Description

      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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Central Review-based Progression-Free Survival

Secondary Outcome

 Overall Survival

Condition

Atypical Carcinoid Tumor

Intervention

Bevacizumab

Study Arms / Comparison Groups

 Arm I (octreotide acetate and bevacizumab)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

427

Start Date

December 1, 2007


Primary Completion Date

January 1, 2015

Eligibility Criteria

        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
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

James C Yao, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00569127

Organization ID

NCI-2009-00778

Secondary IDs

NCI-2009-00778

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

James C Yao, Principal Investigator, Southwest Oncology Group


Verification Date

November 2020