Avastin (Bevacizumab) and RAD001 (Everolimus) in Advanced Low or Intermediate Grade Neuroendocrine Carcinoma

NCT00607113 | Completed Phase 2 Results

• 1 other identifier: 2006-0954
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives:

• To determine the effect of Avastin on tumor blood flow as determined by functional computed tomography (CT) in patients with low or intermediate grade neuroendocrine carcinoma.
• To determine the effect of RAD001 on tumor blood flow as determined by functional CT in patients with low or intermediate grade neuroendocrine carcinoma.
• To determine the effect of adding the second agent (Avastin or RAD001) to the first agent (RAD001 or Avastin) on tumor blood flow as determined by functional CT Secondary Objectives:
• To determine the clinical activity (objective response rate and progression free survival duration) of Avastin and RAD001 in patients with low or intermediate grade neuroendocrine carcinoma.
• To determine the biochemical response rate of Avastin and RAD001 in patients with low or intermediate grade neuroendocrine carcinoma.
• To determine the safety and tolerability of Avastin and RAD001 in patients with low or intermediate grade neuroendocrine carcinoma.

Conditions

Neuroendocrine Carcinoma

Keywords

Neuroendocrine Carcinoma; Avastin; Bevacizumab; RAD001; Everolimus

Outcome Measures

Primary Outcomes (1)

• Net Change Relative to Baseline in Tumor Blood Flow

  Tumor blood flow (ml/min/100gm) determined by functional computed tomography (CT). Functional computed tomography (CT) at baseline, after first and third cycles (21 day cycles). Change (percentage) calculated as tumor blood flow measured at baseline compared to tumor blood flow measurement taken at end of Cycle 1, week 3 (21 days), and again at end of Cycle 3, Week 9 (63 days).

  Baseline to end of Cycle 3 (63 days)

Study Arms (3)

Avastin

EXPERIMENTAL

Cycle 1 (First 3 weeks of study) - Avastin 15 mg/kg intravenous (IV)

Drug: Avastin

Avastin + RAD001

EXPERIMENTAL

Cycle 2: Avastin 15 mg/kg intravenous (IV) every 3 weeks + RAD001 10 mg orally daily for 3 weeks

Drug: Avastin; Drug: RAD001

RAD001

EXPERIMENTAL

Cycle 1 (First 3 weeks of study)- RAD001 10 mg orally daily for 21 Days

Drug: RAD001

Interventions

Avastin DRUG

15 mg/kg By Vein Over 90 Minutes Every 21 Days

Also known as: Bevacizumab

Avastin; Avastin + RAD001

RAD001 DRUG

10 mg By Mouth Daily For 21 Days

Also known as: Everolimus

Avastin + RAD001; RAD001

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 low or intermediate grade neuroendocrine carcinoma. Patients with neuroendocrine tumors associated with MEN1 syndrome will be eligible.
• Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) that has not been previously irradiated. If the patient has had previous radiation to the target lesion(s), there must be evidence of progression in the lesion(s) since the radiation.
• Patients must have at least one lesion suitable for perfusion CT. The lesion should be greater than or equal to 3 cm in size in the cranial caudal direction.
• Patients who are on a somatostatin analogue must be on a stable dose (no change in mg dose of long acting octreotide or lanreotide, changes in dosing interval of +/- 1 week is allowed) for 2 months prior to date of randomization.
• Prior radiation therapy is permitted. A recovery period of at least 4 weeks after completion of radiotherapy is required prior to date of randomization.
• Patients may have received prior interferon or cytotoxic chemotherapy. There are no limitations on the number of prior regimens. Patients who had no prior therapy are eligible. At least 28 days must have elapsed since last treatment.
• Patients may have received prior therapy targeting c-kit, abl, Platelet Derived Growth Factor Receptor (PDGFR), or estimated glomerular filtration rate or epidermal growth factor receptor (EGFR) (imatinib, gefitinib, erlotinib, cetuximab).
• Age \>/= 18 years of age, because no dosing or adverse event data are currently available on the use of bevacizumab and everolimus in patients \< 18 years of age.
• Patients must have unresectable or metastatic disease.
• Zubrod performance status of 0 or 1.
• Patients must have adequate organ and marrow function as defined below: Leukocytes \>/= 3,000/mcL; absolute neutrophil count \>/=1,500/mcL; platelets \>/=120,000 /mcL; total bilirubin \</=1.5 times the institutional upper limit of normal (ULN); aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) \</=3.0 times institutional ULN (\</= 5 \* ULN in patients with liver metastases); creatinine \</= 2.0 OR, creatinine clearance \>/= 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Patients not on anticoagulation must have Prothrombin time (PT)/partial thromboplastin time (PTT) within 1.2 \* the upper limit of normal.
• Patients on full-dose anticoagulation (warfarin or low molecular weight heparin) are eligible provided that both of the following criteria are met: The patient has an in-range INR (between 2 and 3) on a stable (no change in the prior 2 weeks) dose of oral anticoagulant or on a stable (no change in the prior 2 weeks) dose of low molecular weight heparin. The patient has no active bleeding or known pathological condition that carries a high risk of bleeding such as varices.
• Patients must have resting blood pressure (BP) no greater than 140 mmHg (systolic) or 90 mmHg (diastolic) for eligibility. Initiation or adjustment of BP medication is permitted prior to date of randomization.
• Women of child-bearing potential must have a negative urine pregnancy test within 7 days prior to date of randomization. Women who have had menses within the past 2 years, who have not had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy are considered to be of child-bearing potential.

You may not qualify if:

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
• Prior treatment with a mTOR inhibitor or bevacizumab.
• Chronic treatment with systemic steroids or another immunosuppressive agent.
• A known history of immunocompromise, including a positive HIV test. An HIV test will not be required; however, previous medical history will be reviewed.
• Inadequately controlled hypertension (defined as systolic blood pressure \>140 and/or diastolic blood pressure \> 90 mmHg on antihypertensive medications).
• Any 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 date of randomization.
• History of stroke or transient ischemic attack within 6 months prior to date of randomization.
• Known history of brain or leptomeningeal metastases.
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection).
• Symptomatic peripheral vascular disease.
• Evidence of bleeding diathesis or coagulopathy.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to date of randomization or anticipation of need for major surgical procedure during the course of the study.
• Minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to date of randomization.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

U.T.M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Yao JC, Phan AT, Hess K, Fogelman D, Jacobs C, Dagohoy C, Leary C, Xie K, Ng CS. Perfusion computed tomography as functional biomarker in randomized run-in study of bevacizumab and everolimus in well-differentiated neuroendocrine tumors. Pancreas. 2015 Mar;44(2):190-7. doi: 10.1097/MPA.0000000000000255.

  PMID: 25426617 DERIVED

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

Bevacizumab; Everolimus

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. James Yao
• Organization: UT MD Anderson Cancer Center

mjlim@mdanderson.org

713-792-2828

Study Officials

• James Yao, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2008
• First Posted: February 5, 2008
• Study Start: January 1, 2008
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: July 18, 2013
• Results First Posted: May 8, 2013

Record last verified: 2013-05

Locations

US (1)