To Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 386 When Used in Combination With AMG 706, Bevacizumab, Sorafenib, or Sunitinib.

NCT00861419 | Completed Phase 1

• 1 other identifier: 20050170
• Study Type: interventional
• Target: 88
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of AMG 386 when used in combination with AMG 706, bevacizumab, sorafenib, or sunitinib and that at least one dose level from each combination will be safe and well tolerated. AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.

Conditions

Advanced Solid Tumors

Keywords

AMG 386; AMG 706; Bevacizumab; Sorafenib; Angiogenesis Inhibitors; Combination Therapy; Peptibody; Sunitinib

Outcome Measures

Primary Outcomes (1)

• Safety including adverse events, clinically significant changes in laboratory results, ECG, and vital signs, to be measured throughout the study. Pharmacokinetic Profile of AMG 386 - blood levels of AMG 386 to be measured throughout the study.

Secondary Outcomes (1)

• Response based on biomarker, anti-AMG 386 antibody formation and tumor response measure by RECIST.

  End of Study

Study Arms (8)

D

EXPERIMENTAL

3 mg/kg AMG 386 IV (QW) / 125 mg AMG 706 PO (QD)

Drug: AMG 706; Drug: AMG 386

A

EXPERIMENTAL

3 mg/kg AMG 386 IV (QW) / 15 mg/kg bevacizumab IV (Q3W)

Drug: Bevacizumab; Drug: AMG 386

B

EXPERIMENTAL

3 mg/kg AMG 386 IV (QW) / 75 mg AMG 706 PO (QD)

Drug: AMG 706; Drug: AMG 386

E

EXPERIMENTAL

3 mg/kg AMG 386 IV (QW) / 400 mg sorafenib PO (BID)

Drug: Sorafenib; Drug: AMG 386

H

EXPERIMENTAL

10 mg/kg AMG 386 IV (QW) / 50 mg sunitinib PO (QD - 4 weeks on/2 weeks off)

Drug: AMG 386; Drug: Sunitinib

G

EXPERIMENTAL

3 mg/kg AMG 386 IV (QW) / 50 mg sunitinib PO (QD - 4 weeks on/2 weeks off)

Drug: Sunitinib; Drug: AMG 386

C

EXPERIMENTAL

10 mg/kg AMG 386 IV (QW) / 15 mg/kg bevacizumab IV (Q3W)

Drug: AMG 386; Drug: Bevacizumab

F

EXPERIMENTAL

10 mg/kg AMG 386 IV (QW) / 400 mg sorafenib PO (BID)

Drug: Sorafenib; Drug: AMG 386

Interventions

Sorafenib DRUG

Sorafenib 400 mg PO (BID)

Also known as: Nexavar

E; F

AMG 706 DRUG

AMG 706 125 mg PO (QD)

Also known as: Motesanib Diphosphate

D

AMG 386 DRUG

AMG 386 10 mg/kg IV (QW)

C; F; H

Sunitinib DRUG

Sunitinib 50 mg PO (QD)

Also known as: Sutent

G; H

Bevacizumab DRUG

Bevacizumab 15mg/kg IV Q3W

Also known as: Avastin

A; C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women at least 18 years old.
• 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.
• Subjects enrolling in arms E \& F and G \& H must have pathologically documented and definitively diagnosed advanced renal cell carcinoma.
• Measurable disease or evaluable (non-measurable) disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status up to 2.
• Subjects must be able to self-administer AMG 706 (arms B and D) or sorafenib (arms E and F) 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 arms G and H must be able to self-administer sunitinib once daily.

You may not qualify if:

• History of lymphoma or leukemia.
• Symptomatic or untreated central nervous system metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and corticosteroids.
• Subjects with head and neck cancer.
• 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
• For arms A and C: Subjects with ovarian cancer.
• History of arterial or venous thrombosis or pulmonary embolism within 1 year before enrollment; history of bleeding diathesis.
• 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.
• For arms G and H: LVEF ≤ 45%, heart rate \< 50 / min.
• Chronic uncontrolled hypertension \[diastolic \> 85 mmHg; systolic \>145 mmHg\].
• History of pulmonary hemorrhage or gross hemoptysis within 6 months before enrollment.
• History of significant GI surgery or disease, which would impair absorption.
• Active infection within 2 weeks before enrollment.
• Subject known to have tested positive for HIV.
• Subject known to have chronic hepatitis (e.g., hepatitis B or hepatitis C).
• Coumarin anticoagulants including warfarin, at doses greater than 2 mg/day. The concurrent use of low molecular weight heparin or low dose warfarin (ie, ≤ 2 mg daily for prophylaxis against central venous catheter thrombosis is acceptable.

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• Hong DS, Gordon MS, Samlowski WE, Kurzrock R, Tannir N, Friedland D, Mendelson DS, Vogelzang NJ, Rasmussen E, Wu BM, Bass MB, Zhong ZD, Friberg G, Appleman LJ. A phase I, open-label study of trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma. Clin Genitourin Cancer. 2014 Jun;12(3):167-177.e2. doi: 10.1016/j.clgc.2013.11.007. Epub 2013 Nov 13.

  PMID: 24365125 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

Sorafenib; motesanib diphosphate; trebananib; Sunitinib; Bevacizumab

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Pyrroles; Azoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2009
• First Posted: March 13, 2009
• Study Start: December 1, 2005
• Last Updated: February 8, 2017

Record last verified: 2017-02