HKI-272 for HER2-Positive Breast Cancer and Brain Metastases

Breast Cancer Clinical Trial

Official title: A Phase II Trial of HKI-272 (Neratinib), Neratinib and Capecitabine, and Ado-Trastuzumab Emtansine for Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer and Brain Metastases

Status Active, not recruiting

Clinical Trial Summary

The purpose of this research study is to determine how well neratinib works in treating breast cancer that has spread to the brain. Neratinib is a recently discovered oral drug that may stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include Human Epidermal Growth Factor Receptor 2 (HER2).

In this research study, the investigators are looking to see how well neratinib works to decrease the size of or stabilize breast cancer that has spread to the brain. The investigators are also looking at how previous treatments have affected your thinking (or cognition) and how much neratinib reaches the central nervous system.

Clinical Trial Description

Subjects will receive neratinib and a drug-dosing calendar for each treatment cycle. This drug is given orally on a daily basis, continuously. Each treatment cycle will last for 4 weeks during which time the subject will be taking neratinib every day.

• Physical Exams and vital signs: At the start of each cycle, you will have a physical exam. You will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking. You will also have a neurological examination to assess for neurological symptoms.

• Scans (or Imaging tests): We will assess your tumor by brain MRI every 2 cycles ( 6 to 8 weeks) and then every 3 cycles (9 to 12 weeks). CT or MRI scans of your chest, abdomen, and pelvis will be performed every other cycle, at the same time points as the brain MRI. Your research doctor may ask you to have a bone scan at the same time points if this is clinically indicated.

• Photographs: Photographs may be taken of your tumor to assess the response of your tumor to the treatment. Care will be taken to ensure these do not reveal your identity.

• MUGA or Echo: You will have a MUGA or ECHO done every 12 weeks, so every 3 or 4 treatment cycles, depending on which cohort you are on.

• Blood tests: You will have blood tests done at the beginning of each treatment cycle to check your blood cell counts and how well your organs are functioning. In addition to regular blood tests, we will be collecting 2-3 tablespoons of blood for research prior to your study treatment start.

• Neurocognitive Function: If you have previously received treatment for cancer that has spread to your brain (prior to enrollment on this study), you will be asked to take a battery of tests that assess your cognition (thinking) at the start of the study, after 2 cycles of treatment, and possibly at the end of the study. With these tests, we are trying to better understand how your previous treatments and ongoing treatments affect your memory, attention, learning, and other related skills. These tests will be administered to you by a trained research assistant and may take 30-45 minutes to complete.

• For preoperative patients only: If you are a patient who is planning to have an operation to remove the cancer in your brain, you will have your surgery between 7-21 days after starting neratinib. These tests will allow us to measure of how much drug (neratinib) reaches the central nervous system and will help us understand how well neratinib does this.

• At surgery, a part of your tumor cerebrospinal fluid will be collected to test for levels of neratinib. For the cerebrospinal fluid collection, this may require a lumbar puncture just before your surgery begins (spinal tap) if your neurosurgeon feels he/she cannot collect this fluid easily during your surgery. A lumbar puncture is a test often used to detect tumor cells in your cerebrospinal fluid. In this case, we will collect fluid for testing of cancer cells and will also examine the fluid for neratinib concentrations. This will provide information on how much drug (neratinib) reaches the central nervous system. There will be a separate consent form for this procedure given to you by your neurosurgeon (when applicable). This procedure will be done while you are already under general anesthesia for your surgery. If you have a contraindication to having this procedure or if you wish to refuse to undergo this procedure, you may do so.

• You will also have a blood test on day of surgery to test for levels of neratinib

• You will then resume neratinib once you have recovered from your surgery

After the final dose of the study drug:

You will have a follow-up visit one month after coming off study treatment. During that visit, you will have a physical examination, functional assessment, assessment of any toxicities and current medications, and a neurological examination. If you continue to have ongoing toxicity related to your study treatment, we will continue to follow you until this toxicity resolves. In addition, we will collect about 5-6 tablespoons of blood for research and to measure if a marker for your particular breast cancer exists.

We would like to keep track of your medical condition for up to two years after you stop the study treatment. If you are not seen in follow-up at your participating center (where you enrolled on the study), we would like to follow you by calling you on the telephone or by sending you a letter once a year to see how you are doing. We may also contact your doctor once every 6 months to see how you are doing. Keeping in touch with you and checking your condition every year helps us look at the long-term effects of the research study. If you do not wish to be contacted after you stop the study treatment, you must notify the research study staff of your withdrawal of consent for follow-up ;

Related Conditions & MeSH terms

• Brain Neoplasms
• Breast Cancer
• Breast Neoplasms

• NCT number: NCT01494662
• Study type: Interventional
• Source: Dana-Farber Cancer Institute
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 2012
• Completion date: December 2024