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Study Summary
No. 2008-0642:.......Colorectal......Cathy Eng......Gastrointestinal Medical Oncology
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Study Summary Title
Study Summary
Number:
2008-0642
Study Title:A Randomized, Phase 1b/2 Trial of AMG 102 or AMG 479 in Combination with Panitumumab versus Panitumumab Alone in Subjects with Wild-Type KRAS Metastatic Colorectal Cancer (20060447)
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Physician New Patient Referral
Name:Cathy EngPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Gastrointestinal Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2828
Contact us about clinical trials
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General Information
Disease Group:ColorectalSupported By:Amgen
Phase of Study:Phase I/Phase IIReturn
Visit:
Every 2 weeks for the first 49 weeks, then every 12 weeks. If enrolled in part
1, patients will visit the clinic about 4 more times to have extra blood
collected to measure PK levels. The extra visits will be during week 5 - 6.
Treatment
Agents:
AMG 102
AMG 479
Panitumumab
Home Care:NA
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
NA
Description/
Intervention:
Unavailable
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Study Objectives / Outcomes


This protocol consists of 3 parts. Part 1 is the dose finding phase 1b portion of the study. Part 2 is the phase 2, randomized, three-cohort portion of the study. Part 3 is an extension of the phase 2 (part 2) in which select subjects from part 2 may continue treatment in one of two cohorts. Throughout this protocol abstract, the various portions of the study will be referred to as part 1, 2, or 3.

Primary Objectives:
The primary objective of part 1 is to identify a tolerable dose of AMG 102 in combination with panitumumab based on the subject incidence and nature of AEs (AEs) and clinical laboratory abnormalities defined as dose-limiting toxicity (DLTs) in subjects with wild-type KRAS metastatic colorectal cancer (mCRC).

The primary objective of part 2 is to evaluate the efficacy as assessed by the objective response rate of AMG 102 (tolerable dose selected from part 1) in combination with panitumumab and AMG 479 in combination with panitumumab vs. panitumumab alone in subjects with wild-type KRAS mCRC.

The use of a control in part 2 will provide a comparator for AMG 102 or AMG 479 in combination with panitumumab in the target study population.

To explore the efficacy of AMG 102 and AMG 479 monotherapy in part 3.

Secondary Objectives:
Part 1:
1) To evaluate the safety of AMG 102 in combination with panitumumab.

2) Pharmacokinetics (PK) exposure of AMG 102 and panitumumab when given in
combination.

Part 2:
1) To evaluate the safety and efficacy of AMG 102 (tolerable dose selected from
part 1) in combination with panitumumab and AMG 479 in combination with
panitumumab vs. panitumumab alone.

2) PK exposure of AMG 102 and panitumumab when given in combination.

3) PK exposure of AMG 479 and panitumumab when given in combination.

4) PK exposure of panitumumab when given alone.

Exploratory Objectives:
1) Part 1: To evaluate the efficacy of AMG 102 in combination with panitumumab

2) Part 3: To evaluate the safety and efficacy of AMG 102 and AMG 479
monotherapy following treatment with panitumumab (cohort 3) in part 2

3) Pharmacodynamic response of AMG 102 as assessed by hepatocyte growth
factor/c-Met (HGF/c-Met), pathway markers, tumor apoptosis markers,
angiogenic cytokines, and other biomarkers (Part 1, 2, and 3)

4) Pharmacodynamic response of AMG 479 as assessed by insulin-like growth
factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), and
growth hormone (Part 2 and 3)

5) Correlation between plasma HGF levels or tumor ribonucleic acid (RNA)
expression and tumor response (Parts 1, 2, and 3)

6) Tumor genetic variation in pathway genes, cancer genes, drug target genes, and
other biomarker genes on subject response to investigational product (Parts 1,
2, and 3)

7) Effect of genetic variation in cancer genes, drug target genes, drug metabolism
genes, and other biomarker genes on subject response to investigational product
on a subset of subjects (Parts 1, 2, and 3)
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Study Status Information
Study Activation / Registration Date:08/24/2009
IRB Review and Approval Date:05/14/2009
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:Up to 144
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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 metastatic adenocarcinoma of the colon or rectum.

2) Wild-type KRAS tumor status of archival tumor tissue confirmed by an Amgen approved central laboratory or an experienced laboratory (local laboratory) per local regulatory guidelines using a validated test method

3) Radiographic evidence of disease progression during or following prior treatment with irinotecan and/or oxaliplatin based chemotherapy for mCRC.

4) At least 1 uni-dimensionally measurable lesion >/= 20 mm (CT or MRI) or >/=10 (spiral CT) in one dimension per modified Response Evaluation Criteria in Solid Tumors (RECIST v1.0) using conventional techniques (CT scan or MRI) or spiral CT scan. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated.

5) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6) Man or woman >/= 18 years of age

7) A life expectancy estimate of >/= 3 months

8) To be performed </= 7 days before enrollment, unless otherwise specified: Hematologic function within the following limits: a) Absolute neutrophil count (ANC) >/= 1.0 x 10^9 cells/L; b) Platelets >/= 100 x 10^9/L.

9) Renal function within the following limits: Creatinine < 2.0 mg/dL.

10) Hepatic function within the following limits: a) Aspartate aminotransferase (AST) </= 2.5 x ULN (</= 5 x ULN if liver metastases); b) Alanine aminotransferase (ALT) </= 2.5 x ULN (</= 5 x ULN if liver metastases); c) Bilirubin </= 2 x ULN.

11) Magnesium >/= lower limit of normal.

12) Subjects with known diabetes (Type 1 or 2) must have adequate glycemic function, as follows: a) Must be controlled with a glycosylated hemoglobin (HgbA1c) of < 8.0%; b) Documented fasting blood sugars < 160 mg/dL.

13) Negative pregnancy test </= 3 days before enrollment (for woman of childbearing potential only).

14) For Part 3 only: Radiographic evidence of disease progression per modified RECIST, clinical progression, or intolerability during treatment (cohort 3 confirmed upon unblinding).

Exclusion Criteria:1) History of prior or concurrent central nervous system (CNS) metastases.

2) History of other primary cancer, unless: a) Curatively resected non-melanomatous skin cancer; b) Curatively treated cervical carcinoma in situ; c) Other primary solid tumor treated with curative intent and no known active disease present for >/= 5 years before enrollment.

3) Prior treatment with anti-EGFr inhibitors (eg, panitumumab, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting >/= 6 months before enrollment.

4) Prior treatment with c-Met, IGF-IR, or IGF-IIR inhibitors.

5) Prior treatment with either AMG 102 or AMG 479.

6) Use of experimental or approved systemic chemotherapy or radiotherapy </= 21 days before enrollment.

7) Use of experimental or approved targeted therapies </= 30 days before enrollment.

8) Known allergy or hypersensitivity to any component of panitumumab, AMG 102, or AMG 479.

9) History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan.

10) Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) </= 1 year before enrollment.

11) Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as =/> grade 2 per CTCAE version 3.0).

12) Known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection.

13) Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion).

14) Serious or non-healing wound </= 35 days before enrollment.

15) Any uncontrolled concurrent illness (eg, infection, bleeding diathesis) or history of any medical condition that may interfere with the interpretation of the study results.

16) Major surgical procedure </= 35 days before enrollment or minor surgical procedure </= 14 days before enrollment. Subjects must have recovered from surgery related toxicities. Central venous catheter placement, fine needle aspiration, thoracentesis, or paracentesis is not considered a major or minor surgical procedure.

17) Other investigational procedures or drugs (ie, participation in another clinical study) are excluded </= 30 days.

18) Subject of child-bearing potential is evidently pregnant (eg, positive HCG test) or is breast feeding.

19) Man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months after the last dose of the last investigational product (men and women). Adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence.

20) Previously enrolled into this study.

21) Subject unwilling or unable to comply with study requirements.

22) Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.

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Links
Registration Number: NCT00788957
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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