Phase1b to Evaluate Safety of AMG706 in Combination With Paclitaxel or Docetaxel for Breast Cancer

Locally Recurrent and Metastatic Breast Cancer Clinical Trial

Official title:

An Open-label, Dose-finding Study to Evaluate the Safety of AMG 706 in Combination With Paclitaxel or Docetaxel as Treatment for Locally Recurrent or Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00322400
• Other study ID #: 20050200
• Status: Completed
• Phase: Phase 1
• First received: May 4, 2006
• Last updated: July 30, 2013
• Start date: March 2006
• Est. completion date: January 2012

Study information

• Verified date: July 2013
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Therapeutic Goods AdministrationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This open-label, dose-finding, multi-center study is designed to determine the safety and the maximum tolerated dose of AMG 706 given once daily in combination with either weekly paclitaxel (Arm A) or once-every-3 week docetaxel (Arm B) in subjects with locally recurrent or metastatic breast cancer. Secondarily, this study will evaluate the pharmacokinetic (PK) profile of AMG 706 in both treatment arms, the PK profile of paclitaxel in Arm A and the PK profile of docetaxel in Arm B. Additionally, this study will assess objective tumor response and duration of response. Exploratory endpoints include the investigation of potential biomarker development and to assess the effects of genetic variation in drug metabolism genes, cancer genes and drug target genes on subject response to AMG 706 in combination with paclitaxel or docetaxel.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: January 2012
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease.

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

• Female 18 years of age or older.

• Adequate hematologic, renal and hepatic function.

• Competent to comprehend, sign, and date an IRB-approved informed consent form.

• Subjects of childbearing potential and sexually active must provide a negative pregnancy test and use accepted and effective method of contraception.

Exclusion Criteria:

• Prior taxane-containing treatment within 6 months prior to enrollment.

• Prior treatment including chemotherapy and/or endocrine therapy discontinued < 21 days prior to enrollment.

• More than one prior systemic chemotherapy for locally recurrent or metastatic breast cancer.

• Current or prior history of central nervous system metastases.

• History of arterial or venous thrombosis within 1 year prior to enrollment.

• History of bleeding diathesis or bleeding within 14 days prior to enrollment.

• Radiation therapy to a significant portion of bone marrow or prior history of high-dose chemotherapy requiring bone marrow or stem cell support.

• Hypersensitivity to paclitaxel, docetaxel, or drugs using the vehicle cremophor.

• Prior VEGFr targeted therapies within 30 days of enrollment.

• Any anticoagulant therapy within 7 days prior to enrollment, except for warfarin of less than 2mg per day.

• Clinically significant cardiac disease including myocardial infarction or other cardiovascular related event within 1 year before enrollment.

• Uncontrolled hypertension (systolic >150 mmHg; diastolic > 90 mmHg).

• Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive.

• Prior bevacizumab or trastuzumab therapy within 12 weeks of enrollment.

• Non-healing wound, ulcer or fracture.

• Known history of prior episodes of cholecystitis, prior biliary procedure or prior or ongoing biliary disease.

• Unable to take oral medications.

• Not recovered from previous therapies.

• Major surgery within 28 days prior to enrollment.

• Prior malignancy unless treated with curative intent and without evidence of disease for greater than 3 years before enrollment.

• Peripheral neuropathy grade > 1 per CTCAE version 3.0

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Locally Recurrent and Metastatic Breast Cancer

Intervention

Drug:
• Docetaxel
Subjects assigned to Arm B, cohorts will receive 75 or 100 mg/m2 of docetaxel (based on cohort assignment) on Day 1 repeated every 21 days (1 cycle). AMG 706 will be administered concurrently on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond.
• Paclitaxel
Subjects assigned to Arm A will receive 90 mg/m2 of paclitaxel on Days 1, 8 and 15 repeated every 28 days (1 cycle). On Arm A, AMG 706 will be concurrently administered on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond.
• AMG 706
Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days. Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (1)

De Boer RH, Kotasek D, White S, Koczwara B, Mainwaring P, Chan A, Melara R, Ye Y, Adewoye AH, Sikorski R, Kaufman PA. Phase 1b dose-finding study of motesanib with docetaxel or paclitaxel in patients with metastatic breast cancer. Breast Cancer Res Treat. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities (DLTs)		Cycle 1 of treatment. For Arm A, 1 cycle = 28 days. For Arm B, 1 cycle = 21 days	Yes
Secondary	Pharmacokinetics of AMG 706 when administered with paclitaxel (Arm A) or docetaxel (Arm B)		Cycle 1 (Arms A and B) and Cycle 2 Arm B only)	No
Secondary	Pharmacokinetics of paclitaxel (Arm A) when administered with AMG 706		Cycle 1, D1 and D8 for subjects in Arm A only	No
Secondary	Pharmacokinetics of docetaxel (Arm B) when administered with AMG 706		Cycles 1 and 2 for subjects in Arm B only	No
Secondary	Incidence of adverse events and clinical laboratory abnormalities not defined as DLTs		From study entry through 30 days post discontinuation of study treatment	Yes
Secondary	Objective tumor response (complete or partial response) according to modified RECIST		Subjects in Arm A: every 8 weeks until discontuation. Subjects in Arm B:every 6 weeks until discontinuation.	No
Secondary	Duration of response (calculated for those subjects who respond): time from first objective tumor response to objective disease progression or death.		Subjects in Arm A: every 8 weeks until discontuation. Subjects in Arm B:every 6 weeks until discontinuation.	No

External Links

•   AmgenTrials clinical trials website