Capecitabine, Temozolomide, and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors

NCT01525082 | Completed Phase 2 Results DMC FDA Drug

• 6 other identifiers: IRB-22412NCI-2011-03497SU-10282011-8571NET0012END00124593
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to evaluate the effectiveness and safety of a combination of capecitabine, temozolomide and bevacizumab in the treatment of advanced pancreatic neuroendocrine tumors.

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Islet Cell Carcinoma; Recurrent Pancreatic Cancer; Somatostatinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Radiographic Response (RR)

  Tumor response to treatment with the combination of capecitabine \& temozolomide plus bevacizumab in patients with metastatic or unresectable pancreatic neuroendocrine tumors was assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions. Response is defined as: * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome is reported as the number of participants who between 3 and 18 months after treatment initiation achieve CR, PR, or clinical response (PR + CR), each a number without dispersion.

  18 months

Secondary Outcomes (5)

• Treatment-related Toxicity

  18 months

• Progression-free Survival (PFS)

  82 months

• Overall Survival (OS)

  82 mo

• O6-methylguanine DNA Methyltransferase (MGMT) Status by Immunohistochemistry (IHC)

  18 months

• O6-methylguanine DNA Methyltransferase (MGMT) by Promoter Methylation

  18 months

Study Arms (1)

Bevacizumab + Capecitabine + Temozolomide

EXPERIMENTAL

Cycles repeat every 28 days until disease progression, unacceptable toxicity, or withdrawal.

Drug: Capecitabine; Drug: Temozolomide; Biological: Bevacizumab

Interventions

Capecitabine DRUG

Capecitabine by mouth twice daily on Days 1 to 14

Also known as: CAPE, Ro 09-1978/000, Xeloda

Bevacizumab + Capecitabine + Temozolomide

Temozolomide DRUG

Temozolomide by mouth daily on Days 10 to 14

Also known as: SCH 52365, Temodal, Temodar, TMZ

Bevacizumab + Capecitabine + Temozolomide

Bevacizumab BIOLOGICAL

Bevacizumab IV over 30 to 90 minutes on Days 1 \& 15

Also known as: Avastin, anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, rhuMAb VEGF

Bevacizumab + Capecitabine + Temozolomide

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed pancreatic neuroendocrine tumors that are moderately- or well-differentiated
• Metastatic or unresectable disease
• If prior surgical resection \> 5 years before the development of metastatic disease, a separate (recent) histological or cytological confirmation of metastatic disease is required
• If there is substantial clinical ambiguity regarding the nature or source of apparent metastases, clinicians should consider biopsy of lesions to establish diagnosis of metastatic disease
• The site of previous radiotherapy, if the only site of disease, has evidence of progressive disease
• If prior sunitinib and everolimus has been administered, a 2-week wash-out period is required prior to 1st dose on this study
• If prior liver-directed therapies (ie, chemoembolization, radioembolization), target lesions in the liver have demonstrated growth since the liver-directed treatment
• If prior peptide receptor radionuclide therapy (PRRT), target lesions in the liver have demonstrated growth since the liver-directed treatment
• Low-dose aspirin (≤ 325 mg/d) may be continued in subjects at higher risk for arterial thromboembolic disease.
• Primary or metastatic tumor lesion measurable in at least 1 dimension, within 4 weeks prior to entry of study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• ≥ 18 years of age.
• Laboratory values as follows, ≤ 2 weeks prior to randomization:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L (≥ 1500/mm³)
• Platelets (PLT) ≥ 100 x 10e9/L (≥ 100,000/mm³)

You may not qualify if:

• Prior bevacizumab; fluoropyrimidines (eg, capecitabine or 5-fluorouracil, 5FU); or temozolomide
• Poorly-differentiated or high-grade pancreatic neuroendocrine tumors
• Prior full field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to enrollment
• Diagnosis of another malignancy, unless \> 3 years earlier and has been disease-free for \> 6 months following the completion of curative intent therapy, specific eligibility exceptions as follows:
• Curatively-resected non-melanomatous skin cancer
• Curatively-treated cervical carcinoma in situ
• Organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values, if hormonal therapy has been initiated or a radical prostatectomy has been performed
• Other primary solid tumor curatively treated with no known active disease present and no treatment administered for \> 3 years
• Concurrent use of other investigational agents and patients who have received investigational drugs ≤ 4 weeks prior to enrollment
• Known hypersensitivity to capecitabine, temozolomide, or any component of the formulation
• Inadequately-controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 100 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to Day 1

Sponsors & Collaborators

• Shaheen Shagufta: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Carcinoma, Islet Cell; Pancreatic Neoplasms; Somatostatinoma

Interventions

Capecitabine; Temozolomide; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenoma, Islet Cell; Adenoma; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Shaheen Shagufta, Clinical Assistant Professor
• Organization: Stanford University

sshaheen@stanford.edu

650-725-6454

Study Officials

• Shaheen Shagufta, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Clinical Assistant Professor

Study Record Dates

• First Submitted: January 10, 2012
• First Posted: February 2, 2012
• Study Start: December 1, 2012
• Primary Completion: January 1, 2018
• Study Completion: December 31, 2019
• Last Updated: February 6, 2024
• Results First Posted: December 30, 2020

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)