BEP Study Phase I (Bevacizumab, Everolimus, Panitumumab)

NCT00586443 | Completed Phase 1

• 1 other identifier: Pro00001082
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Targeting molecular pathways of tumor growth has become a major focus of anti-cancer treatments. This study aims to investigate the toxicity, pharmacokinetics, and preliminary efficacy of the triplet combination of bevacizumab, RAD001, and panitumumab in patients with refractory solid tumors. This open-labeled, non-randomized phase I trial of bevacizumab, everolimus and panitumumab is designed to assess the safety, tolerability and efficacy of this combination in adult patients with advanced solid tumors.

Conditions

Solid Tumors

Keywords

solid tumors; avastin; Phase I; Phase 1; combination therapy; bevacizumab; RAD001; everolimus; pantitumumab

Outcome Measures

Primary Outcomes (1)

• To determine the MTD/recommended phase II regimen and evaluate safety of panitumumab added to RAD001 plus bevacizumab in adult patients with advanced solid tumors.

  Every cycle (28-days)

Secondary Outcomes (1)

• To preliminarily describe any clinical activity (PR, CR or duration of SD) associated with this regimen

  Every cycle (28-days)

Study Arms (1)

I

OTHER

This is a Phase I safety study. There is only one arm.

Drug: bevacizumab, everolimus, panitumumab

Interventions

bevacizumab, everolimus, panitumumab DRUG

Cohort # subjects Bevacizumab Everolimus Panitumumab * 3 3-6 5 mg/kg IV Q2 weeks 5 mg PO QoD 3.6 mg/kg IV Q2 weeks * 2 3-6 5 mg/kg IV Q2 weeks 5 mg PO QoD 4.8 mg/kg IV Q2 weeks * 1 3-6 10 mg/kg IV Q2 weeks 5 mg PO QD 4.8 mg/kg IV Q2 weeks 1. 3-6 10 mg/kg IV Q2 weeks 10 mg PO QD 4.8 mg/kg IV Q2 weeks 2. 3-6 10 mg/kg IV Q2 weeks 10 mg PO QD 6 mg/kg IV Q2 weeks 3a 10 RPTD\* RPTD\* RPTD\* 3b 10 RPTD\*\* RPTD\*\* RPTD\*\* * Panitumumab and RAD001 started on Day 1, bevacizumab started on Day 15. \*\*Bevacizumab and RAD001 started on Day 1, panitumumab started on Day 15.

Also known as: avastin, RAD001

I

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 confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Disease must be measurable or evaluable by RECIST criteria.
• Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1. Patients must not have had major surgery within the 28 days prior to study day 1 or minor surgical procedures within the 7 days prior to study day 1.
• Age \>18 years.
• Karnofsky performance status \> 70%.
• Life expectancy of at least 3 months.
• Patients must have normal organ and marrow function as defined below:
• \*\*Absolute neutrophil count greater or equal to 1,500/μl; Platelets greater or equal to 100,000/μl; Total bilirubin, less or equal to 1.5 X upper limit of normal (ULN)AST(SGOT)/ALT(SGPT)less or equal to 2.5 X ULN less or equal to 5 X ULN if known hepatic metastases; Creatinine clearance greater or equal to 50 mL/min/m2 for patients with creatinine levels (by Cockroft-Gault equation or 24 hour urine; Hemoglobin \> 9 g/dL; Magnesium \> 1.2 mg/dL; Calcium (corrected for albumin)\> 8.7 mg/dL
• The effect of the investigational drugs on the developing human fetus is not known, but these drugs are likely to be embryo- and feto- toxic. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician and study PI immediately. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within the 28 days prior to day 1 of the study.
• Patients who have received any other investigational agents within the 28 days prior to day 1 of the study.
• Patients with known CNS metastases or centrally-located non-small cell lung cancer.
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg)
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy. Patients on full dose anticoagulation are excluded from this trial.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment (56 days for hepatectomy, thoracotomy, neurosurgery) 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 study enrollment
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
• Serious, non-healing wound, ulcer, or bone fracture
• Proteinuria at screening as demonstrated by Urine protein:creatinine (UPC) ratio greater than 1.0
• 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 study enrollment

Sponsors & Collaborators

• Herbert Hurwitz, MD: lead
• Novartis: collaborator
• Genentech, Inc.: collaborator
• Amgen: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Interventions

Bevacizumab; Everolimus; Panitumumab

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

Study Officials

• Herbert I Hurwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 4, 2008
• Study Start: November 1, 2007
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: November 19, 2014

Record last verified: 2014-11

Locations

US (1)