Bevacizumab in Multiple Phase I Combinations
A Phase 1 Study of Bevacizumab in Combination With 1) Sunitinib, 2) Sorafenib, 3) Erlotinib and Cetuximab, 4) Trastuzumab and Lapatinib
2 other identifiers
interventional
343
1 country
1
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of Avastin™ that can be given in combination with 4 other study drug/drug combinations. It will be given with sunitinib, with sorafenib, with a combination of erlotinib and cetuximab, and with a combination of trastuzumab and lapatinib. The safety and effectiveness of these drug combinations will also be studied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2007
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 10, 2007
CompletedFirst Submitted
Initial submission to the registry
October 11, 2007
CompletedFirst Posted
Study publicly available on registry
October 15, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 29, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
April 29, 2020
CompletedJune 30, 2020
January 1, 2020
12.6 years
October 11, 2007
June 27, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerable Dose (MTD) of Avastin in combination with 4 other study drug/drug combinations
MTD defined by Dose Limiting Toxicity in first 28 day cycle (induction phase)
28 days
Study Arms (4)
Bevacizumab + Sunitinib
EXPERIMENTALArm 1: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sunitinib 12.5 mg orally daily for 4 weeks, then 2 weeks off.
Bevacizumab + Sorafenib
EXPERIMENTALArm 2: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sorafenib 200 mg by mouth daily for 28 Days
Bevacizumab + Erlotinib + Cetuximab
EXPERIMENTALArm 3: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Erlotinib 50 mg By Mouth Daily for 28 Days + Cetuximab loading dose 100 mg/m² IV and maintenance 75 mg/m² on Days 1, 8, 15, 22.
Bevacizumab + Trastuzumab + Lapatinib
EXPERIMENTALArm 4: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Trastuzumab loading dose 2 mg/kg IV then maintenance dose 1 mg/kg IV on Day 1 + Lapatinib 250 mg By Mouth Daily for 21 Days.
Interventions
2.5 mg/kg By Vein Over 90 Minutes.
50 mg By Mouth Daily for 28 Days.
Loading 2 mg/kg by vein then Maintenance 1 mg/kg by vein on Day 1
250 mg By Mouth Daily for 21 Days.
12.5 mg orally daily for 4 weeks, then 2 weeks off.
Loading 100 mg/m² by vein and Maintenance 75 mg/m² by vein on Days 1, 8, 15, 22
Eligibility Criteria
You may qualify if:
- Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- Patients must be three weeks from prior cytotoxic therapy; if they have recovered their blood counts to eligibility levels sooner and have no mucositis or other acute toxicities, they may be treated earlier but no sooner than two weeks after their last chemotherapy. Patients must be two weeks or five half lives from biologic therapy, whichever is shorter.
- ECOG performance status \</= 2 (Karnofsky \>/= 60%).
- Patients must have normal organ and marrow function defined as: absolute neutrophil count \>/= 1,000/mL; platelets \>/=75,000/mL; creatinine \</= 3 X ULN; total bilirubin \</= 2.0; ALT(SGPT) \</= 3 X ULN; Exception for patients with liver metastasis: total bilirubin \</= 3 x ULN; ALT(SGPT) \</= 5 X ULN. Exception for the bevacizumab + erlotinib + cetuximab arm and the bevacizumab + trastuzumab + lapatinib arm: no minimum absolute neutrophil count or platelet count.
- The effects of bevacizumab on the developing human fetus are unknown. Angiogenesis is of critical importance to fetal development, and bevacizumab is likely to have adverse consequences in terms of fetal development. For this reason, 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, for the duration of study participation, and for 30 days after the last dose.
- Ability to understand and the willingness to sign a written informed consent document.
- Life expectancy of at least 3 months.
- Patients with a prior DVT/PE are eligible for treatment if they are receiving or have finished receiving appropriate anticoagulation therapy.
You may not qualify if:
- Patients with hemoptysis within 28 days prior to entering the study.
- Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg on medication).
- Patients with clinically significant cardiovascular disease: history of CVA within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
- Pregnant or lactating women.
- History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
- (For patients on the sunitinib treatment arm and the trastuzumab/lapatinib treatment arm only) Left ventricular ejection fraction of less than 50% unless the patient is receiving an angiotensin-converting enzyme (ACE) inhibitor / angiotensin receptor blocker (ARB) and a beta-blocker.
- (For sorafenib treatment arm only) Hypersensitivity to sorafenib or any component of the formulation.
- (For erlotinib and cetuximab treatment arm only) History of hypersensitivity to erlotinib or any component of the formulation.
- (For erlotinib and cetuximab treatment arm only) History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
- (For trastuzumab and lapatinib treatment arm only) History of hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or any component of the formulation.
- (For trastuzumab and lapatinib treatment arm only) History of hypersensitivity to lapatinib or any component of the formulation.
- Patients with clinically significant gastrointestinal bleeding within 28 days prior to entering the study.
- Patients with hemorrhagic brain metastases.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (2)
Subbiah V, Dumbrava EI, Jiang Y, Thein KZ, Naing A, Hong DS, Fu S, Piha-Paul SA, Tsimberidou AM, Janku F, Meric-Bernstam F, Kurzrock R, Falchook G. Dual EGFR blockade with cetuximab and erlotinib combined with anti-VEGF antibody bevacizumab in advanced solid tumors: a phase 1 dose escalation triplet combination trial. Exp Hematol Oncol. 2020 Apr 20;9:7. doi: 10.1186/s40164-020-00159-1. eCollection 2020.
PMID: 32337094DERIVEDFalchook GS, Moulder SL, Wheler JJ, Jiang Y, Bastida CC, Kurzrock R. Dual HER2 inhibition in combination with anti-VEGF treatment is active in heavily pretreated HER2-positive breast cancer. Ann Oncol. 2013 Dec;24(12):3004-11. doi: 10.1093/annonc/mdt395. Epub 2013 Oct 24.
PMID: 24158411DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Funda Meric-Bernstam, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 11, 2007
First Posted
October 15, 2007
Study Start
October 10, 2007
Primary Completion
April 29, 2020
Study Completion
April 29, 2020
Last Updated
June 30, 2020
Record last verified: 2020-01