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Bevacizumab in Multiple Phase I Combinations
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, November 2008
Sponsored by: M.D. Anderson Cancer Center
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00543504
  Purpose

Primary Objective:

-To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of bevacizumab when used in combinations with:

  • sunitinib
  • sorafenib
  • erlotinib and cetuximab
  • trastuzumab and lapatinib

Secondary Objective:

  • Preliminary descriptive assessment of anti-tumor efficacy of each combination.
  • Assessment of anti-angiogenesis correlates.

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

MedlinePlus related topics: Cancer
Drug Information available for: Sunitinib Sunitinib malate Sorafenib Sorafenib tosylate Erlotinib Erlotinib hydrochloride Bevacizumab Lapatinib Lapatinib Ditosylate Immunoglobulins Globulin, Immune Cetuximab Trastuzumab Malic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase 1 Study of Bevacizumab in Combination With 1) Sunitinib, 2) Sorafenib, 3) Erlotinib and Cetuximab, 4) Trastuzumab and Lapatinib

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

Primary Outcome Measures:
  • To find the highest tolerable dose of Avastin that can be given in combination with 4 other study drug/drug combinations. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 290
Study Start Date: October 2007
Estimated Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Bevacizumab + Sunitinib
Drug: Bevacizumab
2.5 mg/kg IV Over 90 Minutes.
Drug: Sunitinib
12.5 mg PO daily for 4 weeks, then 2 weeks off.
2: Experimental
Bevacizumab + Sorafenib
Drug: Bevacizumab
2.5 mg/kg IV Over 90 Minutes.
Drug: Sorafenib
200 mg PO Daily x 28 Days
3: Experimental
Bevacizumab + Erlotinib + Cetuximab
Drug: Bevacizumab
2.5 mg/kg IV Over 90 Minutes.
Drug: Erlotinib
50 mg PO Daily x 28 Days.
Drug: Cetuximab
100 mg/m^2 IV Weekly Over 2 Hours
4: Experimental
Bevacizumab + Trastuzumab + Lapatinib
Drug: Bevacizumab
2.5 mg/kg IV Over 90 Minutes.
Drug: Trastuzumab
2 mg/kg IV Once Every 3 Weeks
Drug: Lapatinib
250 mg PO Daily x 21 Days.

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • 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 >/= 6 wks beyond treatment with a nitrosourea or mitomycin-C, >/= 4 wks beyond other chemotherapy or XRT, and must have recovered to </= grade 1 toxicity for any treatment-limiting toxicity of prior therapy. (Exception: patients may have received palliative low dose XRT to the limbs 1-4 wks before this therapy provided pelvis, ribs, sternum, scapulae, vertebrae or skull were not included in the XRT field). Also, patients who have received non-chemotherapeutic biologic agents will need to wait at least 5 half-lives or 4 wks, whichever is shorter, from the last day of treatment.
  • 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 </= 2 X ULN; total bilirubin </= 2.0; AST(SGOT)/ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; AST(SGOT)/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.

Exclusion Criteria:

  • 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.
  • Patients with prior abdominal surgery within 30 days prior to entering the study.
  • (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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00543504

Contacts
Contact: Gerald Falchook, MD 713-563-1930

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Gerald Falchook, MD            
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Gerald Falchook, MD U.T.M.D. Anderson Cancer Center
  More Information

MD Anderson Cancer Center  This link exits the ClinicalTrials.gov site

Responsible Party: U.T.M.D. Anderson Cancer Center ( Gerald Falchook, MD/Professor )
Study ID Numbers: 2006-0638
Study First Received: October 11, 2007
Last Updated: November 18, 2008
ClinicalTrials.gov Identifier: NCT00543504  
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
Anti-VEGF monoclonal antibody
rhuMAb-VEGF
Erlotinib hydrochloride
GW572016
Sunitinib Malate

Study placed in the following topic categories:
Erlotinib
Antibodies, Monoclonal
Antibodies
Sunitinib
Cetuximab
Trastuzumab
Lapatinib
Bevacizumab
Sorafenib
Immunoglobulins

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances
Therapeutic Uses
Physiological Effects of Drugs
Enzyme Inhibitors
Growth Inhibitors
Angiogenesis Modulating Agents
Protein Kinase Inhibitors
Angiogenesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009