A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244 (ARRY-142886) When Given in Combination With Standard Doses of Selected Chemotherapies to Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- AZD6244
- Conditions
- Breast Cancer
- Sponsor
- AstraZeneca
- Enrollment
- 140
- Locations
- 1
- Primary Endpoint
- Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies.
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
This study is being conducted to determine if a combination of AZD6244 given orally twice a day with standard doses of selected chemotherapies will be safe and tolerable for cancer patients with advanced solid tumors. The highest tolerated dose of AZD6244 in combination with selected chemotherapies will be evaluated. The study will also investigate how AZD6244 in combination with standard chemotherapies are absorbed, distributed and excreted by the body as well as the length of time that the drugs remain in the body. Initial and periodic assessments will establish patient response to the combination therapies
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients will have measurable and/or non-measurable disease, lacking curative options for whom the selected chemotherapy agents represent the standard of care
- •WHO performance status 0-1
- •Patients must be able to swallow AZD6244 capsules
Exclusion Criteria
- •Prior treatment with a MEK inhibitor
- •Participation in a clinical study during the last 30 days or have not recovered from side effects of an investigational study drug
- •Brain metastases or spinal cord compression unless treated and stable (for at least 1 month) off steroids
Arms & Interventions
1
AZD6244 + docetaxel
Intervention: AZD6244
1
AZD6244 + docetaxel
Intervention: Docetaxel
2
AZD6244 + Dacarbazine
Intervention: AZD6244
2
AZD6244 + Dacarbazine
Intervention: Dacarbazine
3
AZD6244 + Erlotinib
Intervention: AZD6244
3
AZD6244 + Erlotinib
Intervention: Erlotinib
4
AZD6244 + Temsirolimus
Intervention: AZD6244
4
AZD6244 + Temsirolimus
Intervention: Temsirolimus
Outcomes
Primary Outcomes
Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies.
Time Frame: 28 days +
Incidence and intensity of adverse events as graded by CTCAE (version 3.0), physical examinations, vital signs (including weight, blood pressure and pulse rate), ECG parameters, MUGA scan and echocardiography, clinical chemistry (including liver function tests), Brain Natriuretic Peptide (BNP), Troponin I, hematology, urinalysis, and ophthalmologic examinations.
Secondary Outcomes
- PK of AZD6244 and selected chemotherapies.(Cycle 1 Day 3 and Cycle 2 day 1)
- Define highest tolerated dose of AZD6244 when in combination with selected chemotherapies.(28 days +)
- Tumor response.(28 days +)