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Bevacizumab in Multiple Phase I Combinations

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00543504
First received: October 11, 2007
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Advanced Cancer
Drug: Bevacizumab
Drug: Sorafenib
Drug: Erlotinib
Drug: Trastuzumab
Drug: Lapatinib
Drug: Sunitinib
Drug: Cetuximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Bevacizumab in Combination With 1) Sunitinib, 2) Sorafenib, 3) Erlotinib and Cetuximab, 4) Trastuzumab and Lapatinib

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerable Dose (MTD) of Avastin in combination with 4 other study drug/drug combinations [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    MTD defined by Dose Limiting Toxicity in first 28 day cycle (induction phase)


Estimated Enrollment: 354
Study Start Date: October 2007
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab + Sunitinib
Arm 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.
Drug: Bevacizumab
2.5 mg/kg By Vein Over 90 Minutes.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Sunitinib
12.5 mg orally daily for 4 weeks, then 2 weeks off.
Other Names:
  • Sunitinib Malate
  • SU011248
  • Sutent
Experimental: Bevacizumab + Sorafenib
Arm 2: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sorafenib 200 mg by mouth daily for 28 Days
Drug: Bevacizumab
2.5 mg/kg By Vein Over 90 Minutes.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Sorafenib
200 mg By Mouth Daily for 28 Days
Other Name: BAY 43-9006
Experimental: Bevacizumab + Erlotinib + Cetuximab
Arm 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.
Drug: Bevacizumab
2.5 mg/kg By Vein Over 90 Minutes.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Erlotinib
50 mg By Mouth Daily for 28 Days.
Other Names:
  • Erlotinib hydrochloride
  • OSI-774
  • Tarceva
Drug: Cetuximab
Loading 100 mg/m² by vein and Maintenance 75 mg/m² by vein on Days 1, 8, 15, 22
Experimental: Bevacizumab + Trastuzumab + Lapatinib
Arm 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.
Drug: Bevacizumab
2.5 mg/kg By Vein Over 90 Minutes.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Trastuzumab
Loading 2 mg/kg by vein then Maintenance 1 mg/kg by vein on Day 1
Other Name: Herceptin
Drug: Lapatinib
250 mg By Mouth Daily for 21 Days.
Other Names:
  • GW572016
  • Tykerb

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. ECOG performance status </= 2 (Karnofsky >/= 60%).
  4. 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.
  5. 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.
  6. Ability to understand and the willingness to sign a written informed consent document.
  7. Life expectancy of at least 3 months.
  8. Patients with a prior DVT/PE are eligible for treatment if they are receiving or have finished receiving appropriate anticoagulation therapy.

Exclusion Criteria:

  1. Patients with hemoptysis within 28 days prior to entering the study.
  2. Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
  3. Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication).
  4. Patients with clinically significant cardiovascular disease: history of CVA within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
  5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
  6. Pregnant or lactating women.
  7. History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
  8. (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.
  9. (For sorafenib treatment arm only) Hypersensitivity to sorafenib or any component of the formulation.
  10. (For erlotinib and cetuximab treatment arm only) History of hypersensitivity to erlotinib or any component of the formulation.
  11. (For erlotinib and cetuximab treatment arm only) History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
  12. (For trastuzumab and lapatinib treatment arm only) History of hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or any component of the formulation.
  13. (For trastuzumab and lapatinib treatment arm only) History of hypersensitivity to lapatinib or any component of the formulation.
  14. Patients with clinically significant gastrointestinal bleeding within 28 days prior to entering the study.
  15. Patients with hemorrhagic brain metastases.
  16. Patients with prior abdominal surgery within 30 days prior to entering the study.
  17. (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.
  18. (For patients on the sunitinib treatment arm and the trastuzumab/lapatinib treatment arm only) QTc prolongation, defined as greater than 440 milliseconds for males, and greater than 460 milliseconds for females.
  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: NCT00543504

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Funda Meric-Bernstam, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00543504     History of Changes
Other Study ID Numbers: 2006-0638, NCI-2012-01552
Study First Received: October 11, 2007
Last Updated: June 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancer
Bevacizumab
Avastin
Sorafenib
BAY 43-9006
Erlotinib
OSI-774
Tarceva
Trastuzumab
Herceptin
Sunitinib
SU011248
Sutent
Cetuximab
Lapatinib
Tykerb
Anti-VEGF monoclonal antibody
rhuMAb-VEGF
Erlotinib hydrochloride
GW572016
Sunitinib Malate

Additional relevant MeSH terms:
Antibodies, Monoclonal
Bevacizumab
Cetuximab
Erlotinib
Lapatinib
Sorafenib
Sunitinib
Trastuzumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014