Clinical trial NCT00780676
Conditions: Breast Cancer
Keywords: Dasatinib Metastatic Breast Cancer Sprycel BMS-354825 Genetic testing AZD6244 Selumetinib
Sponsor: M.D. Anderson Cancer Center
Start date: 2009-06-01; Completion date: 2014-05-01
Enrollment: 97 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical research study is to learn if researchers can use genetic tests to predict who may benefit from treatment with SprycelTM (dasatinib) or selumetinib (AZD6244).

Detailed description:
The Study Drug:

Dasatinib blocks several different enzymes called protein kinases that are found in cancer cells. These enzymes are important to cancer cell growth. Blocking these kinases may stop or slow cancer growth.

AZD6244 is designed to block the growth of cancer cells by interfering with specific targeted molecules needed for tumor growth, rather than by simply interfering with rapidly dividing cells (like in traditional chemotherapy).

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take either dasatinib or AZD6244. The drug you take will be decided by your doctor based on the findings of the tumor biopsy.

* If you take dasatinib, you will take 2 dasatinib tablets by mouth once every day. The dasatinib tablets will need to be swallowed whole and can be taken with or without a meal.
* If you take AZD6244, you will take 3 tablets by mouth twice every day. The AZD6244 tablet will need to be taken with 8 ounces of water on an empty stomach (1 hour before or 2 hours after a meal) about 12 hours apart.

If you have side effects, the study doctor may decrease your dose or you may stop receiving the study drug for up to 21 days.

While you receive treatment with dasatinib or AZD6244, you may not receive other anti-cancer treatment such as chemotherapy or hormonal therapy.

If you are receiving treatment with a bisphosphonate that is given by vein (such as Aredia or Zometa), you will not be able to receive the drug during the first 8 weeks of this study. This is done in order to avoid low calcium levels in the blood. You may be able to continue to receive the study drug after the first 8 weeks.

Study Visits:

Every 4 weeks while on study, you will have a complete physical exam. Blood (about 3-4 teaspoons) will be drawn for routine tests.

* If you are taking dasatinib, at Week 4, you will have an ECG.
* If you are taking AZD6244, at Week 8, and experience heart-related side effects suggestive of cardiac problems, you will have an ECHO or multiple gated acquisition scan (MUGA).

Every 8 weeks, the scans (such as MRIs, CTs, and bone scans) and x-rays that were performed at screening will be repeated.

If you experience visual disturbances while receiving AZD6244, you will have an eye exam.

Length of Study:

You may continue taking the study drug daily for as long as you are benefitting. You will be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Study Visit:

If you are taken off study because of side effects, you will have CT scans or x-rays to check the status of the disease.

This is an investigational study. Dasatinib is FDA approved to treat chronic myeloid leukemia. It is not yet FDA approved for the treatment of patients with breast cancer. At this time, the use of dasatinib in breast cancer patients is investigational. AZD6244 is not FDA approved or commercially available. Its use in this study is investigational.

The tests that will be used to find out if you can receive treatment with dasatinib or AZD6244 are also investigational.

Up to 769 patients will take part in this study. All will be enrolled at MD Anderson.

Arms: arm 1: Participants predicted to respond to Dasatinib (Sprycel) by predictive gene signature receive dasatinib 100 mg by mouth daily. arm 2: Participants predicted to respond to Dasatinib (Sprycel) by predictive gene signature receive dasatinib 100 mg by mouth daily. arm 3: Participants predicted to respond to Dasatinib (Sprycel) by predictive gene signature receive dasatinib 100 mg by mouth daily. arm 4: Participants predicted to respond to selumetinib/AZD6244 by predictive gene signature (either MEK pathway activity predictor positive or MEK pathway predictor negative) receive selumetinib 75 mg by mouth twice daily (BID).
Interventions: intervention 1: Dasatinib intervention 2: AZD6244
Intervention descriptions: intervention 1: 100 mg tablet by mouth daily intervention 2: 75 mg by mouth twice daily.

Protocol documents: