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Clinical Trials for Treatment of Breast Cancer Brain Metastases

NOTE:  If you are looking for clinical trials that enroll people with stable brain metastases go to clinicaltrials.gov and type "metastatic breast cancer" in the search window. About one third of the nearly 400 trials listed there that are recruiting (or about to recruit) participants allow women with treated and stable brain metastases to enroll.  

This is a Phase l study to determine the proper dose and safety for women with HER2-positive brain metastases. Already approved for certain types of lung cancer, afatinib is an angiogenesis inhibitor that works by preventing the growth of blood vessels into the tumor so that it will be starved of the blood and nutrients it needs. The dosage of afatinib will be gradually increased in four separate groups of patients. To enter this trial one previous treatment for brain metastases must have failed and at least 28 days must have elapsed after whole-brain radiation or radiosurgery. 

This Phase ll non-randomized trial is being conducted in France with Kadcyla (TDM-1), a targeted form of Herceptin. There are two groups in the trial: one for oligometastatic (no metastases outside the brain) or asymptomatic brain metastases and the other for progressing brain metastases after having had surgery, radiosurgery, or whole-brain radiotherapy. People are excluded who have only one brain metastasis. (As of July 20th2018 this trial is not yet opened for recruitment). 

This Phase l/ll trial is for women who have at least two brain metastases. Pembrolizumab will be given every three weeks but radiosurgery will be given to only one of the brain metastases so that a comparison can be made of the effect of Pembrolizumab on brain metastases with and without radiosurgery. Pembrolizumab is an immunotherapy drug that has been approved for melanoma and other cancers. It has been show to penetrate the blood-brain barrier. Previous radiosurgery is permitted if it was not given to the two regions that are the target of this study. Enrollees are not permitted to have had whole-brain radiation therapy. The size of the two targeted lesions must meet the Resist 1.1 criteria and each must be no greater than 4 cm. (As of August 20th2018 this trial is not yet opened for recruitment.)

This Phase l trial is testing the safety and tolerability of AZD1390 in combination with radiation. This new compound blocks cell repair of cancer cells undergoing radiation therapy thus causing them to die. It has been shown to penetrate the brain. Different doses will be given to those enrolled in the trial to find the best dose. 

This study’s goal is to find out whether Her2-positive brain metastases can be controlled with either stereotactic radiosurgery or surgical removal instead of whole brain radiation which is more toxic. Brain metastases can not be greater than 30 mm in size that can not be removed by regular surgery and they cannot have had previous whole brain radiation. Patients with diagnosed leptomeningeal disease are excluded. 

This Phase ll study is looking at the safety and efficacy of Cabozantinib in combination with Herceptin for patients who are Her2 positive and Cabozantinib alone for patients who are Her2 negative. Cabozantinib is an angiogenesis inhibitor that has been shown to help shrink or stabilize breast cancer metastases and may be able to penetrate the blood brain barrier and shrink brain metastases.

This Phase ll trial is looking at whether atezolizumab, a protein which activates the immune system, in combination with radiosurgery can affect breast cancer brain metastases. Atezolizumab has been shown to work in non-small cell lung cancer and bladder cancer. The radiosurgery damages the cancer cells so that they are more visible to the immune system and atezolizumab blocks the shield that cancer cells put up to prevent  the immune system from attacking them.  Patients with prior surgery or whole brain radiation can enroll as long as recent brain progression can be treated by stereotactic radiosurgery and does not have more than 5 new or progressing lesions. Patients with known leptomeningeal disease are excluded.

This is a Phase ll pilot study of the chemotherapy drug eribulin which has already been approved for metastatic breast cancer. It is being looked at for patients who have already been treated with taxanes or anthracyclines. Patients must have measureable brain metastases which are asymptomatic and do not require immediate treatment or have failed to respond to either whole brain radiation or stereortactic radiosurgery. Patients with leptomeningeal disease without brain metastases are excluded both those with both leptomonemeingeal disease and brain metastases can enroll.

This is a randomized Phase II study that includes cohorts of patients with either stable or progressing brain metastases. Patients will be randomized to receive cisplatin plus veliparib, or cisplatin plus a placebo. Both drugs have been shown to cross the blood brain barrier. Veliparib inhibits the ability of cancer cells to fix DNA damage causing them to die. Cisplatin is a chemotherapeutic drug that has shown efficacy in triple negative and BRCA positive breast cancer. Progressing brain metastases must have already been treated with radiation. Disease must be stable for at least 14 days after radiation and 28 days after surgery. This trial treats metastases in and outside the brain.

The purpose of this novel study is to see if brain metastases in women with HER2 positive metastatic breast cancer can be prevented from recurring after being treated with stereotactic radiotherapy or surgical removal. It is a three-arm phase l/ll study. The first arm is a Phase l study of T-DM1 (Kadclya) plus escalating doses of metronomic temozolomide (Temodar), a chemotherapeutic drug used in the treatment of cancer of the brain. The Phase ll study compares T-DM1 alone to T-DM1 plus metronomic temozolomide. A metronomic dose is much smaller than a usual dose, but delivered more frequently. Patients with previous treatment of whole-brain radiation or who have leptomeningeal disease areexcluded from this study.

The purpose of this Phase ll international trial is to evaluate the efficiency and safety of Nal-IRI in patients with HER2-negative breast cancer. Also known as MM-398, this experimental drug is the chemotherapy drug irinotecan hydrochloride encapsulated in a liposome drug delivery system which is thought to penetrate the blood brain barrier. To participate in the trial one previous chemotherapy is required and brain metastases must have progressed after either whole-brain radiotherapy or stereotactic radiotherapy. Having leptomenigeal disease excludes people from
the trial

The purpose of this study is to see if HER2-positive brain metastases can be distinguished from HER2-negative brain metastases using the imaging agent 68-GaNOTA, a radiopharmaceutical agent, used with a PET/CT scan. If it is shown to work it would mean that brain surgery could be avoided to find out whether a brain metastases is HER2-negative or HER2-positive. Brain metastases can differ from the primary breast tumor and other metastases, which may have implications for treatment.

This is a Phase l study to understand the distribution of the chemotherapy drug irinotecan (MM-398) in metastases including the brain. It will also determine the feasibility of ferumoxytol in magnetic resonance imagining in measuring tumor associated macrophages, a part of the immune system that may indicate response to treatments. MM-398 is encapsulated in a liposome which may mean that it is better in getting into the brain than regular chemotherapy.

This trial will compare whole-brain radiation therapy (sparing the hippocampus when possible) to stereotactic radiosurgery (only targeting the metastases) to see which treatment results in a better quality of life. While stereotactic radiotherapy avoids radiation to the whole brain it will likely lead to more recurrences. Patients must have 5-15 metastases with no prior radiation. Patients who have had surgical removal of 1 or 2 metastases may enroll in the trial. Patients with widespread leptomeningeal disease are not eligible.

The purpose of this study is to see if the number and kind of circulating tumor cells before and 4 or 5 weeks after treatment for brain metastases can help determine the aggressiveness of the disease.  In turn, this could help to determine the aggressiveness of treatment. This study is taking place in Brazil.

This single arm study looks at the outcome of stereotactic radiosurgery in patients with 4 or more brain metastases. To qualify, the patient’s tumor must be .5 cm or larger and she can't have had previous whole-brain radiotherapy or stereotactic radiotherapy within 3 months preceding entry into the study. Patients with leptomeningeal disease are excluded. SIMT stands for single-isocenter, multi-target stereotactic radiosurgery which is different than Gamma Knife stereotactic radiosurgery. They appear to have the same efficacy though SIMT is done in a shorter period of time.

This Phase ll study is being done to determine if the form of radiation called tomotherapy is effective for patients with brain metastases or leptomeningeal disease that has not responded to or is progressing after regular whole-brain radiation therapy. Tomotherapy combines computed tomography (CT) with guided intensity modulated radiation therapy (IMRT). The radiation is delivered slice by slice and the intensity or strength of the radiation is targeted to the metastases. Patients must have at least 3 or more brain metastases 6 centimeters or leptomeningeal disease. Patients cannot have received previously stereotactic radiotherapy in any other hospital then where the study is taking place (in
China). 

This a randomized Phase lll trial for patients with metastatic breast cancer and stable brain mets (brain metastases are not progressing). Patients either get the experimental chemotherapy drug etirinotecan or physician's choice out of 7 chemotherapeutic regimes: eribulin, ixabepilone, gemcitabine, paclitaxel, docetaxol and nab paclitaxel given for either primary diagnois or for metastatic disease..Triple negative breast cancer patients must have had at least one prior chemotherapy in the metastatic setting. This drug is a form of irinotecan which remains in cancer tissue longer and is therefore thought to be more effective and less toxic.

The purpose of this Phase ll trial is to see if palbociclib (Ibrance), which has already been approved for ER+ metastatic breast cancer, works for ER- and Her2+ brain metastases. There is preclinical evidence that it does. Patients in the trial must have received no more than two different chemotherapies for metastatic disease and must be no less that 2 weeks out from prior treatment. Previous treatment of brain metastases by surgery or stereotactic radiosurgery is permitted. The targeted lesion must be 5 mm or more in size. Those with uncontrolled symptoms of central nervous system disease or leptomeningeal disease are excluded. Herceptin can be continued for those with Her2+ breast cancer.  

This Phase lb study is looking at the efficacy of a two-stage immunotherapeutic experimental treatment. Toca 511 is a viral vector which carries a modified yeast gene which makes cytosine deaminese in cancer cells. After the virus infects the cell the pill Toca PC is taken which converts the antifungal 5FC intro the anti cancer drug 5-FU. 5-FU is a well researched chemotherapeutic drug used in breast cancer treatment. The vector delivery system targets cancer cells, hopefully avoiding toxicities in healthy cells. This treatment also blocks the cancer cells from evading the immune system. Treatment of Toca 511 will be delivered by lumbar puncture for three consecutive days. After 14 to 28 days the brain metastases will be surgically removed and evaluated for the presence of vector in the tumor. From 4-6 weeks after recovery from surgery, patients will take toca FC, a pill form of Toca 511 for seven days, to be repeated every six weeks. No investigational drug is allowed in the previous two weeks and no prior antibody therapy is allowed within forty-five days.

 This is a Phase 2 double-blinded randomized trial looking at the effect of tucatinib (ONT-380) on women with HER2+metastatic disease with progressing or stable brain metastases. One arm of the study will get tucatinib with trastuzumab (Herceptin) and capecitibine (Xeloda) and the other will get trastuzumab and capecitabine (which is the standard of care) and a placebo. There were high response rates to the combination Tucatinib and TDM-1 (Kadcyla) in a Phase I trial. To enroll in this study you have to have already had a taxane, trastuzumab, pertuzumab (Perjeta), and TDM-1. Brain metastases must be measurable and those with leptomeningeal disease are excluded. 

This is a Phase II study of eribulin, a chemotherapy drug. The FDA has already approved eribulin for metastatic breast cancer. However, this is the first study looking to see if it works for brain metastases. All participants will receive the drug. Prior treatment with whole-brain radiation, stereotactic radiosurgery or surgery are permitted but not required although patients must have some remaining disease that is measurable.

This Phase II study will examine the safety and efficacy of pertuzumab in combination with high-dose Herceptin in people with HER2-positive metastatic breast cancer and central nervous system metastases (excluding leptomeningeal disease). To qualify, patients must have had whole-brain radiation or stereotactic radiosurgery. Both pertuzumab and trastuzumab will be given by IV infusion. This is the first time both drugs will be given in a study of brain metastases, although the combination has been shown to be effective for women with metastatic breast cancer with HER2-positive disease.

This Phase ll study is studying the penetration of the drug afatinib (Gilotrif) into brain metastases for patients having surgical removal of their brain metastases, with or without low-dose targeted radiation. Afatinib is a targeted therapy approved by the FDA for certain kinds of lung cancer that is being studied in a variety of other cancers. In this three-arm randomized study patients will get either no radiation, 2 Gy radiation or 4 Gy radiation prior to surgery. All patients will receive 11 days of afatinib and on day 12 the brain metastasis will be removed. This study is for women presenting with operable brain metastases for the first time including patients with brain metastases when their cancer is first diagnosed.  

 The purpose of this Phase I study is to evaluate the safety of administering a single dose of trastuzumab into the artery for the treatment of brain metastases for HER2 positive breast cancer. It will try to determine the best tolerated single dosage of trastuzumab administered into the artery by gradually increasing the dosage given to participants as the study progresses. Early participants will receive a dosage of 1mg/kg. As more participants enroll in the study, this single dosage will be increased at designated levels up to 8mg/kg if it's determined to be safe to increase. Patents cannot have leptomeningeal disease.

This unrandomized Phase ll trial studies how well pegylated irinotecan (NKTR 102) works in treating breast cancer that has spread to the brain. Pegylation keeps the chemotherapy for a longer period of time in the cancer cells than in normal cells. This experimental agent may stop the growth of tumor cells by blocking enzymes needed for cell growth. Findings from earlier studies suggest that this agent may be effective in breast cancer brain metastases. Patients with either newly diagnosed brain metastases or lesions that have progressed after radiation are eligible. Patients with known leptomeningeal disease must be approved by the sponsor and the principal investigator of the trial.

The purpose of this randomized study is to see if prophylactic (preventative) cranial (whole brain) radiation in patients with metastatic triple negative breast cancer can prevent or lengthen the time before brain metastases might occur. Patients must have had a response to first line chemotherapy in the metastatic setting to be eligible for the trial. Patients will be randomized to radiation or observation. Both safety and efficacy of prophylactic cranial radiation will be measured.    

This Phase ll non-randomized clinical trial is testing the safety and effectiveness of an already FDA approved drug (for another cancer)  to see if it works for breast cancer that has spread to the brain. Phase l studies suggests that cabozantinib may help to shrink or stabilize metastases from breast cancer. In addition, previous studies have shown that cabozantinib may pass through the blood brain barrier which is necessary to treat brain metastases. All patients will receive cabozantinib and if they are HER2-positive they will receive trastuzumab (Herceptin). Patients with newly diagnosed brain metastases or with progressive brain metastases are eligible for the trial. Those with leptomeningeal disease as the only site of central nervous system disease are not eligible.

This is a Phase II non-randomized clinical trial to test the safety and efficacy of abemaciclib in hormone receptor positive metastatic breast cancer that is no longer responding to hormonal treatment. Patients can have either Her2+ or Her2- disease. They must have already completed local therapy brain metastases (whole-brain, stereotactic radiation, or surgical removal of brain metastases) and not require any local therapy immediately.  Abemaciclib is a CDK 4/6 inhibitor which blocks cancer cell growth and replication.

In this Phase ll trial, patients will be randomized to receive either the regular treatment of whole brain radiotherapy or the experimental treatment of bevacizumab (Avastin), etoposide and cisplatin prior to whole brain radiotherapy. The thinking behind this experimental strategy is that giving chemotherapy first might shrink the brain metastases, thus making the radiotherapy more effective. Bevacizumab given one day before the etoposide and cisplatin is believed to make the vessels around the tumor less leaky, hopefully ensuring that a larger amount of etoposide and cisplatin is delivered to the metastases. A previous study has shown that  women with recurrent brain metastases after whole brain radiation had an excellent response to the bevacizumab given prior to etoposide and cisplatin. Of these 35 patients 27 or 77% acheived at lease a 50% shrinkage of their brain metastases. The sponsors of this trial predict that this kind of approach will benefit all tumor types, whether ER-positive, ER-negative, or HER2-positive. 

The purpose of this Phase l trial is to study the safety and proper dose for sorafenib, a pill given together with whole brain radiotherapy for women with breast cancer that has metastasized to the brain. Sorafenib controls cell growth by blocking proteins that cause tumor cells to grow. It also decreases the blood supply to the tumor. It has already been approved by the FDA for liver and kidney cancer. Eligible participants may have had a recurrence in the brain after stereotactic radiosurgery.

This study has two components. The first component is a research study comparing which imaging technique tells us more about the the effect of WBRT on brain metastases. A pet scanner with a new radioactive marker 18F FLT PET will be compared to an MRI. The amount of radiation is small and disappears from the body in a few hours. In addition patients will be randomized to get sorafenib or not with WBRT. Sorafenib controls cell growth by blocking proteins that cause tumor cells to grow and it also decreases the blood supply to the tumor. It has been approved by the FDA for liver and kidney cancer.

This study will look at whether lower doses (hypofractionated) image-guided radiation surgery to metastases in different organs will lower the number of circulating tumor cells in the body and extend survival. Patients with metastases in lung, liver, abdomen and extremeties will receive 10 or less doses of hypofractioned doses of radiation and those with brain metastasis will receive a single dose of stereotactic radiation therapy.

The purpose of this Phase II trial is to see whether giving lapatinib (Tykerb) to patients with Her2-positive breast cancer combined with whole-brain radiotherapy is better than giving whole-brain radiotherapy alone. Patients must have progressive disease after surgical removal of the brain metastases or after stereotactic radiosurgery, as well as measurable disease (tumor 10 mm or more). Those with leptomeningeal disease are excluded.Modified whole brain radiotherapy: Hippocampal-avoidance radiotherapy 

 This randomized trial being offered in China compares two types of whole-brain radiation therapy: one arm avoids radiating the hippocampus and the other does not. The purpose of the study is to see if avoiding the hippocampus results in less neurological decline (decline in mental abilities). The hippocampus is thought to be the part of the brain where memory and cognition is centered. 

This is a randomized Phase lll trial. All patients will receive memantine hydrochoride ( Namenda ) which is a drug shown to improve memory and cognition when given to patients together with whole-brain radiotherapy. Then patients will be randomized to receive regular WBRT or WBRT that does not radiate the hippocampal region of the brain. The hippocampal region of the brain plays an important role in memory and understanding and shielding it from radiation may improve memory and cognition after WBRT. However, it is not known whether not radiating the hippocampal region might increase the risk for recurrences in the brain. Patients must not have had prior WBRT and brain metastases must be 5mm or more from the hippocampus. Patients with leptomeningeal disease do not qualify.

This two-arm randomized trial is being conducted in Germany.  It compares the cognitive function (understanding, learning, and memory) of WBRT versus WBRT that avoids radiation to the hippocampal region of the brain, where memory and cognition are stored. The intent is to study and compare both arms in terms of cognition, recurrence in the brain, and overall survival. It is not known if avoiding the hippocampal region of the brain may increase the chance of recurrence in that area.

This Phase II single arm study is being conducted in Taiwan. All patients will receive WBRT that avoids the hippocampal region of the brain, where memory and cognition are stored, to see if shielding it from radiation improves cognition and memory. No brain metastases can be larger than 4 cm and patients can't have leptomeningeal disease.

This Phase ll randomized trial is taking place in Taiwan. Patients in the trial will receive either conformational WBRT that avoids the hippocampal region of the brain, where memory and cognition are stored, or conformational WBRT that includes the hippocampus. All brain metastases must be at least 5cm from the hippocampus. Patients with leptomeningeal disease are excluded.

This is a Phase ll trial looking at a different type of whole brain radiotherapy known as IMRT, which delivers higher doses of radiation to brain metastases while delivering a lower dose of radiation to the rest of the brain. The hope is that the part of the brain without clinical brain metastases will not need as high a dose as the areas that have brain metastases, and that delivering less radiation will reduce toxicity and cognitive side effects.Clinical Trials for Radiation-Caused Necrosis

This is a single center study of 15 patients with brain lesions being treated at University of North Carolina Hospital. Patients will undergo one FLT-PET-MRI scan before their scheduled surgical biopsy.