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Study Summary
No. 2007-0275:.......Lung......George Blumenschein......Thoracic and Head and Neck Med
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Study Summary Title
Study Summary
Number:
2007-0275
Study Title:A Phase 2, Multicenter, Open-Label, Randomized Trial of AMG 706 or Bevacizumab in Combination with Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer.
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Physician New Patient Referral
Name:George BlumenscheinPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Thoracic and Head and Neck MedReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-6363
Contact us about clinical trials
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General Information
Disease Group:LungSupported By:AMGEN
AMGEN
Phase of Study:Phase IIReturn
Visit:
The screening period may need 2 or 3 visits.
There are approximately 6 cycles of treatment.
Each cycle is approximately every 3 weeks.
Visit every week for the first 6 weeks
One additional visit approx. 1 month after your last study treatment.
Treatment
Agents:
AMG 706
Bevacizumab
Carboplatin
Paclitaxel
Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to find out whether the study drug,
AMG 706, (given in 2 different regimens) given in combination with standard
chemotherapy (paclitaxel and carboplatin) is better able to control stage IIIB
or IV non-squamous NSCLC as compared to bevacizumab given in combination with
standard chemotherapy. Researchers will also study the safety of AMG 706 when
given in combination with chemotherapy.
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Study Objectives / Outcomes
Primary Objective:
  • To estimate the difference in objective response rates between each paclitaxel/carboplatin plus AMG 706 arm (Arms A and B) and the paclitaxel/carboplatin plus bevacizumab arm (Arm C) in subjects with advanced non-squamous NSCLC.

Secondary Objectives:
  • To estimate the duration of response, progression-free survival, and overall survival in each of the 3 treatment arms
  • To evaluate the safety and tolerability in the 3 treatment arms
  • To evaluate the pharmacokinetics of AMG 706 when administered with paclitaxel and carboplatin in Arms A and B

Exploratory Objectives:
  • To investigate potential biomarker development based on assessment of blood cells and tumor cells and the proposed mechanism of action of study drug and response
  • To investigate the effects of genetic variation in drug metabolism genes, cancer genes and drug target genes on subject response to AMG 706 or bevacizumab in combination with paclitaxel and carboplatin (separate informed consent form)
  • To investigate patient reported outcomes (PRO).
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Study Status Information
Study Activation / Registration Date:03/11/2008
IRB Review and Approval Date:06/22/2007
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual: 180
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Histologically or cytologically confirmed advanced non-squamous NSCLC (unresectable stage IIIB with pericardial or pleural effusion or stage IV/recurrent)

2) Measurable disease per RECIST criteria modified

3) ECOG performance status of 0 or 1

4) Life expectancy of >/= 3 months as determined by the investigator

5) Men or women >/= 18 years old

6) Hematological function, as follows: - Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L - Platelet count >/= 100 x 10^9/L and </= 850 x 10^9/L - Hemoglobin >/= 9 g/dL

7) Renal function, as follows: - Creatinine clearance > 40 mL/minute (calculated or measured) - Urinary protein quantitative value of </= 30 mg in urinalysis or </= 1+ on dipstick unless quantitative protein is < 500 mg in a 24-hour urine sample

8) Hepatic function, as follows: - Aspartate aminotransferase (AST) </= 2.5 x upper limit of normal (ULN) OR AST < 5 x ULN if liver metastases are present Alanine aminotransferase (ALT) </= 2.5 x ULN OR ALT < 5 x ULN if liver metastases are present - Alkaline phosphatase </= 2.0 x ULN OR alkaline phosphatase < 5 x ULN if liver or bone metastases are present - Total bilirubin < 1.5 ULN OR if total bilirubin < 3 X UNL if subject has UGT1A1 promoter polymorphism (ie, Gilbert syndrome) confirmed by genotyping or Invader® UGT1A1 Molecular Assay prior to randomization

9) Partial thromboplastin time (PTT) </= 1 x ULN AND International normalized ratio (INR) </= 1.5 x ULN

10) Competent to give written informed consent

11) Ability to take oral medications

12) Plan to begin protocol directed therapy within 7 days after randomization

Exclusion Criteria:1) Current or prior history of central nervous system (CNS) metastases

2) Prior history of other primary cancer unless: - Curatively resected non-melanomatous skin cancer - Curatively treated cervical carcinoma in situ - Other solid tumor curatively treated with no known active disease present and no curative treatment administered for the last 3 years

3) Prior chemotherapy as follows: - Any prior chemotherapy for advanced NSCLC - Any prior adjuvant chemotherapy for NSCLC within 52 weeks prior to randomization. Adjuvant chemotherapy completed > 52 weeks prior to randomization is permitted - Any prior chemoradiation for locally advanced stage III disease

4) Prior radiation therapy as follows: - central (chest) radiation therapy within 28 days prior to randomization - other radiation therapy within 14 days prior to randomization - radiation therapy to a site of measurable disease unless there has been documented disease progression

5) History of pulmonary hemorrhage or gross hemoptysis (˝ teaspoon of bright red blood or more) within 6 months prior to randomization

6) Prior targeted therapies, including but not limited to: - AMG 706, inhibitors of VEGF (eg, SU5416, SU6668, AZ6474, SU11248, PTK787, AZD2171, AEE-788, BAY 43-9006, bevacizumab), or EGFr (eg, cetuximab, gefitinib, erlotinib)

7) Known history of allergy or hypersensitivity reaction to paclitaxel or carboplatin

8) Any anticoagulation therapy within 7 days prior to randomization except the use of low-dose warfarin < 2 mg daily] or low molecular weight heparin or heparin flushes for prophylaxis against central venous catheter thrombosis which is allowed

9) Chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents known to inhibit platelet function. Treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is also not allowed

10) History of arterial or venous thrombosis within 52 weeks prior to randomization

11) History of bleeding diathesis or non-pulmonary bleeding within 14 days prior to randomization

12) Peripheral neuropathy > grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

13) Myocardial infarction, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, percutaneous transluminal coronary angioplasty/stent, ongoing arrythmias requiring medication or unstable angina within 52 weeks prior to randomization

14) Any kind of disorder that compromises the ability to comply with the study procedures

15) Uncontrolled hypertension as defined by resting blood pressure >140/90 mm Hg. Anti-hypertensive medications are allowed if hypertension is stably controlled at the time of randomization

16) Surgery: - Major surgery within 30 days prior to randomization - Minor surgery within 14 days prior to randomization - Failure to recover from prior surgery - Planned elective surgery while on study - Placement of central catheter within 7 days prior to randomization - Core needle biopsy within 7 days prior to randomization

17) Not recovered from all previous therapies (ie, radiation, surgery and medications). CTCAE grade at screening must be ≤ Grade 1 or the subject's baseline prior to their most recent previous therapy

18) Open wound, ulcer or fracture

19) Active infection requiring systemic treatment or any uncontrolled infection ≤ 14 days prior to randomization

20) Participation in therapeutic clinical trials or currently receiving other investigational treatment(s) within 30 days prior to randomization

21) Pregnant (eg, positive HCG test) or breast feeding woman

22) Man or woman not consenting to use adequate contraceptive precautions (eg, hormonal, barrier or abstinence) during the course of the study and for 6 months after the last treatment

23) Known to be human immunodeficiency virus (HIV), hepatitis B surface antigen or hepatitis C positive

24) History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results

25) Previously randomized into this study

26) Not available for follow-up assessments or unable to comply with study requirements
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Links
Registration Number: NCT00369070 Study Information on Clinical Trials Registry (clinicaltrials.gov)
Other Links:
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Results
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