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Study Summary
No. 2005-0626:.......Colorectal; Lung; Solid Tumors......Razelle Kurzrock......Investigational Cancer Therapeutics
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Study Summary Title
Study Summary
Number:
2005-0626
Study Title:A Phase 1, Open-Label, Dose Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of AMG 655 in Subjects with Advanced Tumors
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Physician New Patient Referral
Name:Razelle KurzrockPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Investigational Cancer TherapeuticsReferring 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:Colorectal
Lung
Solid Tumors
Supported By:N/A
Phase of Study:Phase IReturn
Visit:
Patients will return to MDACC during Study Weeks 1, 2, 3, 5, 6, 7, 8, 9 and
every 8 weeks thereafter; 4 weeks following the last dose and 8 weeks following
the last dose (if feasible).
Treatment
Agents:
AMG 655Home Care:N/A
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 655 that can be given to patients with advanced solid tumors or NHL.
Researchers will also study the level of the study drug in the blood at
different times, and how the body breaks down the drug. This is called
pharmacokinetic (PK) testing. The effect of the study drug on the tumor will
also be studied. If you are enrolled in Part 2 of this study, tissue biopsies
will be required to help researches understand how AMG 655 is affecting you and
your cancer.
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Study Objectives / Outcomes
PRIMARY OBJECTIVES:

1. To assess the safety, tolerability, pharmacokinetics (PK), -(Parts 1 and 2: Escalation and Expansion), and to determine the maximum tolerated dose (MTD), if reached -(Part 1 only), of AMG 655 following multiple intravenous (IV) administrations in adult subjects with histologically documented advanced tumors that are refractory to standard therapy or for which no curative therapy is available.
2. To investigate evidence of tumor necrosis factor-related apoptosis-inducing ligand receptor-2 (TR2) pathway activation in pre and post treatment tumor biopsy as demonstrated by doubling of in situ expression of activated caspase 3 or caspase 8 from pre and post biopsy samples (Part 2 only).

SECONDARY OBJECTIVES:

1. To measure the tumor response by modified Response Evaluation Criteria in Solid Tumors (RECIST) or the International Working Group Response Criteria for non-Hodgkin's Lymhoma;
2. To determine whether human anti-human antibodies (HAHA) to AMG 655 develop in subjects with advanced tumors.

EXPLORATORY OBJECTIVES:
    1. To measure caspase 3/7 activity, cytokeratin 18 (CK18) epitopes M30/M65 and genomic deoxyribonucleic acid (gDNA) in the blood;
    2. To assess tumor glucose metabolism using positron emission tomography scanning with the tracer fluorodeoxyglucose (^18FDG-PET);
    3. To assess tumor volume by computed tomography (CT);
    4. To investigate potential biomarker development by biochemical analysis in blood cells and tumor cells;
    5. To investigate the effects of genetic variation in drug metabolism genes, cancer genes and drug target genes on subject response to AMG 655 (optional; separate informed consent required);
    6. To determine the level of TR2 receptor occupancy of AMG 655 using laser scanning cytometry (LSC);
    7. To determine the pro- and anti-apoptotic protein levels in pre- and post-treatment biopsies.
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Study Status Information
Study Activation / Registration Date:12/16/2005
IRB Review and Approval Date:10/19/2005
Study Type:Phase I
Recruitment Status:Closed
Projected Accrual:Up to 85 subjects are expected to participate in this study
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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) Pathologically documented and definitively diagnosed, advanced solid tumor or Hodgkin's and non-Hodgkin's lymphomas that is refractory to standard treatment or for which no curative therapy is available

2) Eastern Cooperative Oncology Group (ECOG) performance status </= 1

3) Part Two: subjects must have tumor tissue that is accessible for biopsy (ultrasound guided fine needle biopsy or core biopsy) by using minimally invasive procedures and must consent to undergo biopsies of the tumor

4) Men and women (using adequate birth control) >/= 18 years old

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

6) Before any study-specific procedure, the appropriate written informed consent must be obtained

7) Able to fast for 4-6 hrs for ^18FDG-PET/CT scan, except subjects with prostate and bladder cancers

Exclusion Criteria:1) Primary central nervous system (CNS) tumors, including primary CNS lymphoma

2) Hematological malignancies, other than peripheral Hodgkin's and non-Hodgkin's lymphomas

3) Previous hematopoietic stem cell transplant

4) Involvement of > 50% of non-Hodgkin lymphoma or Hodgkin lymphoma in the bone marrow and/or evidence of features of myelodysplasia in the bone marrow

5) Unresolved hematological toxicities > grade 1 with the exception of grade 2 lymphopenia and non-hematological toxicities > grade 1 from prior anti-cancer therapy, excluding alopecia

6) Presence of untreated or symptomatic central nervous system metastases or symptoms of brain metastases

7) Presence of ascites or pleural effusion requiring medical intervention

8) Myocardial infarction within 1 year of study Day 1, or unstable or uncontrolled disease/condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association > class II, uncontrolled hypertension [diastolic > 90 mmHg; systolic >150 mmHg]

9) Cardiac arrhythmia or CTCAE grade >/= 2 or ECG abnormalities

10) History of arterial or venous (deep vein) thrombosis within 1 year of study Day 1

11) History of bleeding diathesis

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

13) Major surgery within 1 month of study Day 1

14) Unable to tolerate intravenous administration

15) Known sensitivity to mammalian derived products

16) Absolute neutrophils count (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 2 weeks of study Day 1); or hemoglobin < 9 g/dL (without transfusion within 4 weeks of study Day 1); or PT/PTT > 1.5 x institutional upper limit of normal (ULN).

17) Estimate of glomerular filtration rate (GFR) < 60 mL/min by Cockroft and Gault equation or by 24-hour urine collections at the discretion of the PI

18) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 x ULN

19) Total bilirubin, amylase or lipase > 1.5 ULN

20) Urinary protein excretion of greater than 100 mg per day (2+, 3+, or 4+ using dipstick analysis)

21) Concurrent antitumor treatment or chemotherapy, radiotherapy and hormonal therapy, except Lupron for prostate cancer and SERMS for breast cancer subjects, within 4 weeks (6 weeks for nitrosoureas or mitomycin) of study Day 1

22) Antibody therapy for the treatment of underlying malignancy within 4 weeks prior to study Day 1, with the exception of bevacizumab (AvastinŽ) and other monoclonal antibodies with a half- life of greater than 10 days which, must be discontinued at least 8 weeks prior to study Day 1.

23) Investigational agent within 30 days of study Day 1

24) Any elective surgeries scheduled during their participation in the study, and through 28 days after their last administration of AMG 655

25) Concurrent or prior (within 30 days of study Day 1) anticoagulation therapy (low-dose warfarin (< 2 mg/day) for prophylaxis against central venous catheter thrombosis is allowed)

26) Concurrent use of herbal medications

27) Concurrent immunosuppressant therapy (cyclosporine A, FK506, etc., or chronic > 5mg/d of prednisone)

28) Other investigational procedures are excluded

29) Subject who is pregnant (e.g., positive human choriogonadotropin test) or breastfeeding

30) Subject of childbearing potential, or subject who has a partner of childbearing potential, is not using adequate contraceptive precautions

31) Subject will not be available for follow-up assessment

32) Subject has any kind of disorder that compromises the ability of the subjects to given written informed consent and/or comply with study procedures

33) Any co-morbid medical condition that would increase the risk of toxicity (in the opinion of the investigator or sponsor)

34) Subject has known sensitivity to any of the products to be administered during dosing

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Links
Registration Number: Not Registered

Other Links:
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Results


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