Phase II Capecitabine, Oxaliplatin & Bevacizumab for Metastatic / Unresectable Neuroendocrine Tumors

NCT00398320 | Completed Phase 2 Results DMC

• 5 other identifiers: IRB-0623397273NET0002NCT00398320END0002 (formerly)
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Given the lack of other viable treatment options for metastatic neuroendocrine tumors, contrasted with our positive anecdotal experience, and the relative tolerability of the treatment regimen for colorectal cancer patients, we propose a single-institution phase II trial investigating the efficacy of capecitabine, oxaliplatin and bevacizumab for patients with metastatic neuroendocrine tumors.

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (2)

• 12-month Progression Free Survival (PFS)

  Percentage of participants with 12-month progression-free survival (PFS) was assessed. PFS is defined as the time from enrollment until documented disease progression or death (whichever occurred first). RECIST criteria (version 1). Complete response (CR) defined as disappearance of all target lesions. Partial Response (PR) defined as ≥ 30% decrease of SLD. Progressive disease (PD) defined as ≥ 20% increase in Sum Longest Diameters (SLD). Stable Disease (SD) defined as being between 20% increase and \< 30% decrease in SLD.

  PFS assessed every 3 months through 12 months

• Number of Patients Who Experienced Treatment-related Grade 3 or Higher Adverse Events by CTCAE Version 3.0

  Participants were monitored every 3 weeks while on study. Toxicity and attributions were as per CTCAE version 3.0 guidelines. Analysis population below is patient who experienced related Grade 3 or higher AE; denominator is 40 total patients enrolled.

  30 days after last treatment

Secondary Outcomes (3)

• Response Rates

  Response rates by RECIST criteria assessed every 3 months while on treatment

• Overall Survival (OS)

  Continuous

• Biochemical Markers

  Assessed every 3 weeks while on treatment

Study Arms (1)

Bevacizumab (Avastin), Oxaliplatin (Eloxatin)

EXPERIMENTAL

Drug: Capecitabine; Drug: Oxaliplatin; Drug: Bevacizumab

Interventions

Capecitabine DRUG

850 mg/m2 by mouth twice a day for days 1-14 oa a 21 day cycle

Bevacizumab (Avastin), Oxaliplatin (Eloxatin)

Oxaliplatin DRUG

130 mg/m2 intravenously on day 1 of a 21 day cycle

Bevacizumab (Avastin), Oxaliplatin (Eloxatin)

Bevacizumab DRUG

7.5mg/kg Intravenous on day 1 of a 21 day cycle

Bevacizumab (Avastin), Oxaliplatin (Eloxatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed neuroendocrine tumor, including both well-differentiated tumors (carcinoid) or moderately to poorly differentiated tumors. Patients must be deemed unresectable due to involvement of critical vasculature, adjacent organ invasion, or presence of metastasis.
• Patients with prior surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of \> 5 years has elapsed between the primary surgery and the development of metastatic disease. Clinicians should consider biopsy of lesions to establish diagnosis of metastatic disease if there is substantial clinical ambiguity regarding the nature or source of apparent metastases.
• Prior chemotherapy will be permitted, although the patient may not have had prior oxaliplatin.
• Patients must have a primary or metastatic lesion measurable in at least one dimension by Modified RECIST criteria (see Section 4.2) within 4 weeks prior to entry of study
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Patients must be ≥ 18 years of age
• Laboratory values ≤ 2 weeks prior to randomization:
• Absolute Neutrophil Count (ANC) \>=1500/mm3
• Platelets (PLT) ≥ 100,000/mm3
• Hemoglobin (Hgb) ≥ 9 g/dL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN if liver metastases present)
• Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), and alkaline phosphatase ≤ 3.0 x ULN (≤ 5.0 x ULN if liver metastases present). Note: Endoscopic retrograde cholangiopancreatogram (ERCP) or percutaneous stenting may be used to normalize the liver function tests.
• Life expectancy ≥ 12 weeks
• Ability to give written informed consent according to local guidelines

You may not qualify if:

• Prior oxaliplatin for any reason.
• Prior full field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to enrollment. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease.
• Prior biologic or immunotherapy ≤ 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities
• Prior therapy with anti-vascular endothelial growth factor (VEGF) agents
• If history of other primary cancer, subject will be eligible only if she or he has:
• Curatively resected non-melanomatous skin cancer
• Curatively treated cervical carcinoma in situ
• Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 3 years
• Concurrent use of other investigational agents and patients who have received investigational drugs ≤ 4 weeks prior to enrollment.
• \. Subjects known to have chronic or active hepatitis B or C infection 2. History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results 3. Male subject who is not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of second-line treatment 4. Female subject (of childbearing potential, post-menopausal for less than 6 months, not surgically sterilized, or not abstinent) who is not willing to use an oral, patch or implanted contraceptive, double-barrier birth control, or an intrauterine device (IUD) during the course of the study and for 6 months following the last dose of second-line treatment 5. Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization 6. Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2 dyspnea) 7. Any of the following concurrent severe and/or uncontrolled medical conditions within 24 weeks of enrollment which could compromise participation in the study:
• Unstable angina pectoris
• Symptomatic congestive heart failure
• Myocardial infarction ≤ 6 months prior to registration and/or randomization
• Serious uncontrolled cardiac arrhythmia
• Uncontrolled diabetes

Sponsors & Collaborators

• Pamela L. Kunz: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

Capecitabine; Oxaliplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Pamela L Kunz, MD
• Organization: Stanford University School of Medicine

pkunz@stanford.edu

650-725-8738

Study Officials

• Pamela L Kunz, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 31, 2006
• First Posted: November 10, 2006
• Study Start: November 1, 2006
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: March 1, 2017
• Results First Posted: December 10, 2013

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)