Combination of Bevacizumab, Pertuzumab, and Sandostatin for Adv. Neuroendocrine Cancers

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01121939
First received: May 10, 2010
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Neuroendocrine Carcinoma
Neuroendocrine
Drug: Bevacizumab
Drug: Pertuzumab
Drug: Sandostatin LAR® Depot
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of the Combination of Bevacizumab, Pertuzumab, and Sandostatin for Patients With Advanced Neuroendocrine Cancers.

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Determine overall response rate of patients with low grade neuroendocrine cancer when treated with the combination of bevacizumab, pertuzumab and sandostatin LAR®. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To determine overall response rate of patients with low grade neuroendocrine cancer when treated with the combination of bevacizumab, pertuzumab and sandostatin LAR®.


Secondary Outcome Measures:
  • define the toxicity and safety [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    To define the toxicity and safety of the combination of bevacizumab, pertuzumab and Sandostatin LAR® when used in patients with advanced low grade neuroendocrine cancer.


Enrollment: 43
Study Start Date: May 2010
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
combination of bevacizumab, pertuzumab, and sandostatin for patients with advanced neuroendocrine cancers
Drug: Bevacizumab
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.
Other Name: Avastin
Drug: 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.

Other Names:
  • Omnitarg
  • 2C4
Drug: Sandostatin LAR® Depot
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.
Other Name: Octreotide

Detailed Description:
  • To determine overall response rate of patients with low grade neuroendocrine cancer when treated with the combination of bevacizumab, pertuzumab and sandostatin LAR®.
  • To determine the disease control rate (objective response + stable disease), time to treatment progression, progression-free survival, and overall survival in patients with advanced low grade neuroendocrine cancer when treated with bevacizumab, pertuzumab and Sandostatin LAR® treatment.
  • To define the toxicity and safety of the combination of bevacizumab, pertuzumab and Sandostatin LAR® when used in patients with advanced low grade neuroendocrine cancer.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01121939

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
United States, Georgia
Medical Oncology Associates of Augusta
Augusta, Georgia, United States, 30901
United States, Kentucky
Baptist Medical Center East
Louisville, Kentucky, United States, 40207
United States, Michigan
Grand Rapids Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Missouri
Research Medical Center
Kansas City, Missouri, United States, 64132
United States, New Jersey
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07960
United States, Ohio
Oncology Hematology Care, Inc
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Tennessee Oncology Associates
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Genentech
Investigators
Study Chair: Johanna C Bendell, S.B., M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01121939     History of Changes
Other Study ID Numbers: SCRI GI 135
Study First Received: May 10, 2010
Last Updated: March 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
advanced neuroendocrine
Gastrointestinal
Bevacizumab
Avastin
Pertuzumab
Omnitarg
2C4
Sandostatin
Octreotide

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Neuroendocrine
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue
Octreotide
Bevacizumab
Pertuzumab
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014