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

• Status: Completed
• Trial end date: 2019-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shaheen Shagufta; Stanford University
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Bevacizumab; Capecitabine; Dacarbazine; Immunoglobulins; Temozolomide

Criteria

INCLUSION CRITERIA

• 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)

• Hemoglobin (Hgb) ≥ 9 g/dL

• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)

• Serum bilirubin ≤ 1.5 x ULN

• Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) ≤ 3.0 x ULN (≤ 5.0 x ULN if liver metastases present). Note: endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous stenting may be used to normalize the liver function tests

• Urine dipstick or urinalysis for protein, value must be 0, trace, or 1+ protein to enroll. EXCEPTION: if ≥ 2+ must check 24-hour urine protein and must be < 1 g

• Life expectancy ≥ 12 weeks

• Ability to give written informed consent according to local guidelines

• If any prior therapy-related toxicities, must have recovered from all

EXCLUSION CRITERIA Disease-Specific Exclusions

• 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

• Known deficiency of dihydropyrimidine dehydrogenase Bevacizumab-specific Exclusions

• 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

• Known central nervous system (CNS) metastases

• Significant vascular disease (eg, aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1

• History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month prior to Day 1

• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1

• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1

• Serious, non-healing wound, active ulcer, or untreated bone fracture

• Known hypersensitivity to any component of bevacizumab General Medical Exclusions

• Inability to comply with study and/or follow-up procedures

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study

• Pregnant or lactating/breast feeding

• Lack of effective contraception men or women of child-bearing potential

• Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)

• Known history of HIV, HBV, or HCV

• Current, ongoing treatment with full-dose warfarin. However, patients may be on stable doses of a low-molecular weight heparin are allowed [eg, (enoxaparin (Lovenox)].