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Study Summary
No. 2005-0794:.......Solid Tumors......David S. Hong......Phase I Program
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Study Summary Title
Study Summary
Number:
2005-0794
Study Title:An Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 386 with AMG 706 and AMG 386 with Bevacizumab and AMG 386 with Sorafenib and AMG 386 with Sunitinib in Adult Patients with Advanced Solid Tumors
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Physician New Patient Referral
Name:David S. HongPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Phase I ProgramReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-1226
Contact us about clinical trials
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General Information
Disease Group:Solid TumorsSupported By:N/A
Phase of Study:Phase IReturn
Visit:
Subjects will return every week.
Treatment
Agents:
AMG 386
AMG 706
Bevacizumab
Sorafenib
Sunitinib Malate
Home Care:Beginning at Day 1 of Cohorts 2, 4, 5, 6, 7, and 8, patients will be asked to
self-administer AMG 706 daily or sorafenib twice daily on an empty stomach.
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of AMG 386 that can be given in combination with AMG 706, Avastin®
(bevacizumab), Nexavar® (sorafenib), or Sutent® (sunitinib). The safety and
effectiveness of these 4 different drug combinations will also be studied.
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Study Objectives / Outcomes
PRIMARY OBJECTIVES:
  • the safety and tolerability of AMG 386 when used in combination with AMG 706, bevacizumab, sorafenib or sunitinib.
  • the pharmacokinetic (PK) profile of AMG 386 when used in combination with AMG 706, bevacizumab, sorafenib or sunitinib.
  • the PK profile of AMG 706 when used in combination with AMG 386.
  • The PK profile of sorafenib when used in combination with AMG 386.
  • The PK profile of sunitinib and the active metabolite when used in combination with AMG 386.

SECONDARY OBJECTIVES:
  • the pharmacodynamic (PD) profile of AMG 386 with AMG 706 or AMG 386 with bevacizumab and AMG 386 with sorafenib, and AMG 386 with sunitinib as assessed by angiogenic cytokines and tumor apoptosis markers
  • tumor response as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)

EXPLORATORY OBJECTIVES:
  • To investigate the effects of genetic variation in drug metabolism genes, cancer genes, and drug target genes on subject response to study treatments. This part of the study is optional.
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Study Status Information
Study Activation / Registration Date:02/16/2006
IRB Review and Approval Date:12/21/2005
Study Type:Phase I
Recruitment Status:Closed
Projected Accrual:81
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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) Subjects must have a pathologically documented, and definitively diagnosed, advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or for subjects who refuse standard therapy

2) Subjects enrolling in cohorts 6-7 and 10-11 must have pathologically documented and definitively diagnosed advanced renal cell carcinoma

3) Measurable disease or evaluable (non-measurable) disease per RECIST guidelines

4) ECOG performance status of </= 2

5) Life expectancy of > 3 months as documented by the investigator

6) Hematological function as follows: ANC >/= 1.5 x 10^9/L (without granulocyte colony stimulating factor support within 2 weeks of study Day 1); platelet count >/= 100 x 10^9/L (without transfusion within 4 weeks of study Day 1); hemoglobin > 9 g/dL (without transfusion within 4 weeks of study Day 1)

7) Men or women >/= 18 years old

8) Renal function as follows: creatinine < 2.0 mg/dL for cohorts 1-4; creatinine <2 x ULN for cohorts 6-7 and 10-11, 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

9) Hepatic function as follows: AST < 2.5 x ULN (if liver metastases are present, </= 5 x ULN); ALT < 2.5 x ULN (if liver metastases are present, </= 5 x ULN); alkaline phosphatase < 2.0 x ULN (if bone or liver metastases are present, </= 5 x ULN); bilirubin < 2.0 x ULN

10) Prothrombin time (PT) or partial thrombolastin time (PTT) < 1.5 x ULN

11) Able to tolerate oral medications and infusions

12) Subjects enrolling in cohorts 2, 4, 6, and 7 must be able to self-administer AMG 706 or sorafenib on an empty stomach (fasting for 1 hour before and 1 hour postdose) once daily for AMG 706 or twice daily for sorafenib. Subjects enrolling in cohorts 10-11 must be able to self-administer sunitinib once daily. All subjects receiving AMG 706, sorafenib, or sunitinib must be able to maintain a record of drug accountability. Additionally, subjects must have radiographically documented tumor progression while on prior bevacizumab treatment.

13) Willing to provide existing and/or future paraffin-embedded tumor samples

14) Female subject is post-menopausal (no menstrual period for a minimum of 12 months), surgically sterilized, using an oral or implanted contraceptive, using a double-barrier birth control or an intrauterine device and is willing to use contraception for 6 months following the last study drug administration and has a negative serum pregnancy test upon entry into this study

15) Male subject is willing to use contraception upon enrollment, during the course of the study, and for 3 months following the last study drug administration

16) Competent to comprehend, sign, and date an institutional review board (IRB)-approved informed consent form.

Exclusion Criteria:1) History of lymphoma or leukemia

2) Symptomatic or untreated central nervous system metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and corticosteroids

3) Subjects with head and neck cancer

4) Subjects with lung squamous cell tumors or with large central (located adjacent to or within the hilum or mediastinum) tumor lesions >/= 3 centimeters, regardless of histology

5) For the bevacizumab/AMG386 cohorts: Subjects with ovarian cancer

6) History of arterial or venous thrombosis or pulmonary embolism within 1 year before enrollment; history of bleeding diathesis

7) Myocardial infarction within 12 months before enrollment, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication

8) Chronic uncontrolled hypertension (diastolic > 85 mmHg; systolic > 145 mmHg)

9) History of pulmonary hemorrhage or gross hemoptysis within 6 months before enrollment

10) History of significant GI surgery or disease, which would impair absorption

11) Active infection within 2 weeks before enrollment

12) Subject known to have tested positive for HIV

13) Subject known to have chronic hepatitis (e.g., hepatitis B or hepatitis C)

14) Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to CTCAE grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia

15) Any co-morbid medical condition that would increase the risk of toxicity

16) For subjects in cohorts involving AMG 706, sorafenib, or sunitinib (2, 4, 6, 7, 10 and 11 ) the following therapies and treatments are excluded: concurrent or prior rifampin phenobarbitol (within 2 weeks before enrollment); strong CYP 3A inhibitors such as ketoconazole, itraconazole, clairithromycin, erythromycin, nefazodone, grapefruit (i.e. whole fruit or fruit juice), or any HIV protease inhibitors (within 1 week prior to enrollment); immune modulators such as cyclosporine and tracrolimus (within 1 week prior to enrollment)

17) Continued from #17: St.John's Wort or any herbal therapy containing St.John's Wort (within 1 week prior to enrollment); Coumarin anticoagulants including warfarin, at doses greater than 2 mg/day. The concurrent use of low molecular weight heparin or low dose warfarin (i.e., </= 2 mg daily for prophylaxis against central venous catheter thrombosis is acceptable

18) Prior anti-tumor therapies: treatment with anti-cancer therapy within 30 days before study day 1 (including chemotherapy, retinoid, vaccine or tumor directed antibody therapy) except for treatment with bevacizumab within 42 days of study day 1, unless prior written approval is received from sponsor

19) For cohorts 1-4, prior treatment with bevacizumab, sorafenib, sutent or investigational agents known to directly inhibit the functions of VEGFR, angiopoeitins, or angiopoeitin receptors, unless prior written approval received from the sponsor

20) For cohorts 6-7, prior treatment with sorafenib, unless prior writeen approval is received from the sponsor.

21) For cohorts 10-11, prior treatment with sunitinib, unless prior written approval is received from the sponsor. For cohorts 6 and 7, 10 and 11, treatment with bevacizumab within 42 days before study day 1, unless prior written approval is received from the sponsor.

22) Known allergy to the excipients, or study drugs

23) History of allergic reactions to bacterially-produced proteins

24) Prior treatment with AMG 386

25) Subject has previously entered this study

26) Major surgery within 30 days before enrollment or recovering from prior surgery

27) Subject who is pregnant or nursing

28) Any disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures

29) Prior radiation therapy to the abdomen

30) Cardiovascular events within 1 year before enrollment, such as myocardial infarction, unstable/severe angina, coronary/peripheral artery bypass graft, unstable cardiac arrhythmia requiring medication, symptomatic congestive heart failure (New York Heart Association >class II), cerebrovascular accident or transient ischemic attack; LVEF </= 45% (for cohorts 10 and 11); Heart rate < 50 / min (for cohorts 10 and 11)

31) Prior anti-tumor therapies: Hormonal anti-tumor therapy within 30 days before enrollment. Does not include hormones for non-cancer related conditions (e.g., insulin for diabetes, RT) or the use of GnRH agonists for prostate cancer; therapeutic or palliative radiation therapy within 2 wks before enrollment (subjects must have resolution of any significant AEs from radiation therapy received prior to 2 wks before enrollment)

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Links
Registration Number: NCT00861419
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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