Combination of Bevacizumab, Pertuzumab, and Sandostatin for Adv. Neuroendocrine Cancers
Condition: Neuroendocrine Carcinoma
MeSH terms: Carcinoma, Neuroendocrine
Intervention: Bevacizumab; Pertuzumab; Sandostatin LAR® Depot
Intervention description: 15 mg/kg IV Day 1. The first dose should be administered over
90 minutes. If no adverse reactions occur after the initial dose, the second dose should
be administered over a minimum of 60 minutes. If no adverse reactions occur after the
second dose, all subsequent doses should be administered over a minimum of 30
minutes. Bevacizumab will be infused prior to pertuzumab.; 840 mg IV loading dose infused over 60 minutes. The loading dose is given on Cycle 1, Day 1 or as below. Subsequent doses of pertuzumab are 420 mg IV. If the patient tolerates the initial infusion over 60 minutes, the patient may receive subsequent infusions over 30 minutes. Otherwise, pertuzumab should be infused over 60 minutes. Patients should be observed for 30 minutes after completing the pertuzumab infusion.
If a patient misses a dose of pertuzumab for 1 cycle (i.e., 2 sequential cycles or administrations are 6 weeks or more apart), a re-loading dose (840 mg) of pertuzumab should be given. If re-loading pertuzumab is administered, subsequent doses of 420 mg will then be given every 3 weeks, starting 3 weeks later.; 30 mg will be given every 28 days by IM injection. The dose of sandostatin may be increased, at the discretion of the treating physician, if necessary to control symptoms related to tumor secretion of vasoactive peptides.
Intervention MeSH terms: Bevacizumab; Pertuzumab; Octreotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced neuroendocrine; Gastrointestinal; Bevacizumab; Avastin; Pertuzumab; Omnitarg; 2C4; Sandostatin; Octreotide

Summary:

      The purpose of this Phase II trial will be to define the activity of a VEGF inhibitor

      bevacizumab, HER1/HER2 inhibitor pertuzumab, and sandostatin for patients with

      advanced neuroendocrine cancers. In particular, the efficacy of bevacizumab and

      pertuzumab treatment is of great interest. The primary endpoint of this trial will be

      response rate. Toxicity and progression-free survival will be obtained and evaluated.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with biopsy-proven advanced, unresectable or metastatic, well-differentiated
             (or low-grade) neuroendocrine carcinoma, including typical carcinoid, pancreatic islet
             cell and other well-differentiated neuroendocrine carcinomas.

          2. Patients with documented evidence of disease progression.

          3. Patients currently receiving or previously treated with single agent Sandostatin LAR®
             are eligible.

          4. Patients must have >=1 unidimensional measurable lesion definable by

             MRI or CT scan. Disease must be measurable per RECIST version 1.1 criteria.

          5. Left Ventricular Ejection Fraction (LVEF) >=50% as determined by either ECHO or MUGA
             <=6 weeks prior to study entry.

          6. An ECOG Performance Status of 0-2.

          7. Laboratory values as follows:

               -  ANC >=1500/μL

               -  Hgb >=9 g/dL

               -  Platelets >=100,000/μL

               -  AST/SGOT <=2.5 x ULN or <=5.0 x ULN in patients with liver metastases

               -  ALT/SGPT <=2.5 x ULN or <=5.0 x ULN in patients with liver metastases

               -  Bilirubin <=1.5 x ULN

               -  Creatinine <=2.0 mg/dL or calculated creatinine clearance >=50 mL/min

          8. Patients >=18 years of age.

          9. Patients must have a life expectancy >12 weeks.

         10. Patient must be accessible for treatment and follow-up.

         11. Women of childbearing potential must have a negative serum or urine pregnancy test
             performed <=7 days prior to start of treatment. Women of childbearing potential must
             use effective birth control measures during treatment. If a woman becomes pregnant or
             suspects she is pregnant while participating in this study, she must agree to inform
             her treating physician immediately.

         12. Patients must be able to understand the nature of the study and give

        written informed consent, and comply with study requirements

        Exclusion Criteria:

          1. Patients with poorly differentiated neuroendocrine carcinoma, highgrade neuroendocrine
             carcinoma, adenocarcinoid, goblet cell carcinoid, atypical carcinoid, anaplastic
             carcinoid, and small cell carcinoma are not eligible.

          2. Previous treatment with VEGF or EGFR inhibitors.

          3. Cytotoxic chemotherapy, immunotherapy or radiotherapy <=4 weeks prior to study entry.

          4. History or known presence of central nervous system (CNS) metastases.

          5. Patients who have had a major surgical procedure (not including mediastinoscopy), open
             biopsy, or significant traumatic injury <=4 weeks prior to beginning treatment.

          6. Female patients who are pregnant or lactating.

          7. History of hypersensitivity to active or inactive excipients of any component of
             treatment (bevacizumab, sandostatin, and/or pertuzumab).

          8. Patients with proteinuria at screening as demonstrated by urine dipstick for
             proteinuria >=2+ (patients discovered to have >=2+ proteinuria on dipstick urinalysis
             at baseline should undergo a 24-hour urine collection, and must demonstrate <=1 g of
             protein/24 hours to be eligible).

          9. Patients with a serious non-healing wound, active ulcer, or untreated bone fracture.

         10. Patients with evidence of bleeding diathesis or significant coagulopathy (in the
             absence of therapeutic anticoagulation).

         11. Patients with history of hematemesis or hemoptysis (defined as having bright red blood
             of ½ teaspoon or more per episode) <=1 month prior to study enrollment.

         12. History of myocardial infarction or unstable angina <=6 months prior to beginning
             treatment.

         13. Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and
             /or diastolic blood pressure >100 mmHg while on antihypertensive medications).
             Initiation of antihypertensive agents is permitted provided adequate control is
             documented at least 1 week prior to Day of study treatment.

         14. New York Heart Association (NYHA) grade II or greater congestive

             heart failure (CHF).

         15. Serious cardiac arrhythmia requiring medication.

         16. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or
             recent peripheral arterial thrombosis) <=6 months prior to Day 1 of treatment.

         17. History of stroke or transient ischemic attack <=6 months prior to beginning
             treatment.

         18. Any prior history of hypertensive crisis or hypertensive encephalopathy.

         19. History of abdominal fistula or gastrointestinal perforation <=6 months prior to Day 1
             of beginning treatment.

         20. Concurrent severe, intercurrent illness including, but not limited to, ongoing or
             active infection, or psychiatric illness/social situations that would limit compliance
             with study requirements.

         21. Any known positive test for human immunodeficiency virus, hepatitis C virus or acute
             or chronic hepatitis B infection.

         22. Mental condition that would prevent patient comprehension of the nature of, and risk
             associated with, the study.

         23. Use of any non-approved or investigational agent <=28 days prior to administration of
             the first dose of study drug. Patients may not receive any other investigational or
             anti-cancer treatments while participating in this study.

         24. Past or current history of neoplasm other than the entry diagnosis with the exception
             of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other
             cancers cured by local therapy alone and a DFS >=5 years.

         25. Infection requiring IV antibiotics.