Do we know if the Pertuzmab crosses BB

[dchips1]

Hello
Do we know if the Pertuzmab crosses the blood brain barrier? IE for brain spinal mets?

Thanks To All who post and lurk here, This has been my resource and i send many here for support and good research

Darita

[chrisy]

No, Pertuzumab is a large molecule, so it generally would not cross the BBB.

[dchips1]

If you take Pertuzumab with herceptin and maybe Tykerb wouldnt you think it would change the HER2 cells from furthur growing? reducing the overall "rogue cells" hiding wating to seed in and grow?

Darita

[pibikay]

this query is for all but paricularly for Lani.After the rad was over (as our son in the US had come over) we had a discussion with the Onc.He said a new drug for which trial is over but not yet ckered will be the next option.I was woncering if he was refering to pertuzmab.The discussion was centered round Hema's brain mets.Is there any thing else on the line.Thankks

[Lani]

from brainmetsBC.org website:


Clinical Trials for Treatment of Breast Cancer Brain Metastases
HKI-272 (neratinib) for HER2-Positive Breast Cancer and Brain Metastases

This phase ll study is to determine how well HKI-272 (neratinib) works in treating breast cancer brain metastases. Neratinib is a recently discovered oral drug that may stop breast cancer cells from growing abnormally by blocking the Her 2 receptor (as well as other receptors in the same). The purpose of the trial is to see if neratinib can shrink or stablize brain metastases in women with either newly diagnosed or recurrent brain metastases. Women must have Her 2 positive disease as well as measurable brain metastases.

Patients may include those who have received or have not received previous treatment(s) for their brain metastases. Those whose tumors are amenable to surgery will have a surgical resection.The trial will also be looking at cognitive function (ability to think) both before and after neratinib.

A Study of Everolimus, Trastuzumab and Vinorelbine in Her2 Positive Breast Cancer Brain Metastases

This is a phase ll study to see if adding everolimus (Afinitor) to vinorelbine (Navelbine) and trastuzumab (Herceptin) is effective, safe and tolerable for women with Her2-positive breast cancer that has metastasized to the brain. All those enrolled will receive the experimental drug. Everolimus was recently found to extend progression-free survival for women with ER+ metastatic disease without brain metastases.

Lapatinib for Brain Metastases in Erb2 (Her2) Positive Breast Cancer

This is a phase ll study to look at the how safe and effective lapatinib (Tykerb) is when used to treat patients with with Her2-positive breast cancer that has spread to the brain and is still progressing after whole-brain or stereotactic radiation therapy (ongoing, but not recruiting).

GRN1005 Alone or in Combination with Trastuzumab in Breast Cancer Patients with Brain Metastases

The purpose of this phase ll study is to assess the efficacy, safety, and tolerability of GRN1005 in patients with Her2-positive breast cancer metastasized to the brain. GRN1005 is a taxane that has been shown to penetrate the blood-brain barrier. Patients will receive it alone or in combination with Herceptin. Patients with and without prior whole-brain radiation can enroll although they must have at least one measurable brain lesion that is 1.0 centimeter or more.

Lux-Breast 3; Afatinib Alone or in Combination With Vinorelbine in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer Suffering From Brain Metastases

This is a randomized phase II study to investigate the safety and efficacy of afatinib, an oral inhibitor of the Her1 and Her2 receptor. It is for women with Her2-positive breast cancer whose brain metastases are progressing after Herceptin or lapatinib (Tykerb). Women will be randomized to receive afatinib alone, in combination with vinorelbine (Navelbine), or investigator's choice of treatment. Prior surgery, whole-brain radiotherapy or stereotactic radiosurgery is allowed, provided there is at least one measureable metastasis after completion of whole brain radiotherapy or stereotactic radiosurgery.

TPI 287 in Breast Cancer Brain Metastases

The goal of this research study is to learn if TPI-287 can control recurrent breast cancer brain metastases. TPI-287 is a novel type of taxane designed to penetrate the blood brain barrier. Patients must have measurable disease on MRI that has progressed after prior therapy. Progressive disease is defined as an appearance of new lesions on a scan, or clinical or neurologic worsening despite stable disease on the last 2 scans. Patients may have had any number of prior surgeries, radiation and/or chemotherapy regimens.

A Study of Herceptin (Trastuzumab) in Combination With Whole Brain Radiotherapy in Patients With HER-2 Positive Breast Cancer

This single-arm phase l study which will evaluate the efficacy and safety of Herceptin (trastuzumab) in combination with whole brain radiotherapy on brain metastases in patients with HER-2 positive breast cancer. At least one measureable brain metastasis is required.

Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in ErbB2 (HER2) Positive Metastatic Breast Cancer

This phase lll randomized study is designed to evaluate lapatinib’s effect on incidence on brain metastases in ErbB2 (HER2) positive metastatic breast cancer patients exposed to prior taxanes or anthracyclines.

A Study Evaluating Iniparib in Combination with Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis

This is a phase II non-randomized trial for women with estrogen receptor, progesterone receptor, and Her-2 negative breast cancer that has metastasized to the brain. It will combine a new drug, iniparib (also known as BSI-201), with Irinotecan, a chemotherapy agent. Iniparib is a member of a new class of drugs called PARP inhibitors which specifically targets triple negative and BRCA 1 and 2 positive breast cancer. Iniparib has shown unusually good results in phase I and II trials of women with triple negative metastatic breast cancer, most without brain metastases. These results are being studied in larger randomized phase III trials. There is emerging evidence that some PARP inhibitors can penetrate the blood-brain barrier.

The trial is accepting two groups of women. The first group is women with new or progressing brain metastases greater than 5 millimeters after prior intracranial radiation (either whole brain or stereotactic radiation). The second group is women with newly diagnosed brain metastases less than 5 millimeter who have not received any type of radiation and whose physicians have decided that they don't need emergency radiation. They must receive treatment in the trial within 2 weeks of diagnosis. There is also an expanded access study for women who don't qualify for the trial, but they must have stable brain metastases (see next entry).

An Open-Label Expanded Access Protocol of Iniparib Breast Cancer

This expanded access trial makes iniparib available before drug approval by the FDA. Iniparib is being offered in combination with gemcitabine and carboplatin for women with triple negative breast cancer (estrogen, progesterone, and Her-2 negative tumors) metastatic breast cancer. Women with stable brain metastases are eligible. Women receiving steroids or expected to require other therapeutic intervention during study participation, including WBRT and intrathecal therapy are not eligible and patients must be more than 21-days from neurosurgical intervention. Brain metastases requiring steroids or expected to require other therapeutic intervention during study participation, including WBRT and intrathecal therapy. Patients must be > 21-days from neurosurgical intervention.

Lapatinib and WBRT For Patients with Brain Metastases from Lung or Breast Tumors

This is a non-randomized Phase ll study to evaluate the response rate (tumor shrinkage) for brain metastases from lung or breast tumors being treated with WBRT and lapatinib (Tykerb). Lapatinib will be continued for six weeks after radiation.

Bevacizumab With Etoposide and Cisplatin in Breast Cancer Patients with Brain and/or Leptomeningeal Metastases

The purpose of this phase ll trial is to investigate the efficacy of bevacizumab (Avastin) in combination with two chemotherapies etoposide and cisplatin. Available only in Taiwan.

Lapatinib (Tykerb) Plus Caelyx in Patients With Advanced Metastatic Breast Cancer Following Failure of Trastuzumab Therapy

This is a phase II randomized study comparing lapatinib and caelyx to lapatinib and doxorubicin (Adriamycin). Caelyx is the Euopean name for Doxil which is doxorubicin (Adriamycin) in a liposome (encapsulated in a gel-like substance). It is thought that this liposomal delivery system may target brain metastases more than regular doxorubicin. To enroll in this trial, women must have received only one previous treatment for metastatic disease.

Carboplatin and Bevacizumab (Avastin) for Progressive Breast Cancer Brain Metastases

This phase II study will look at how well the combination of these two agents will work in metastatic breast cancer that has spread to the brain. Carboplatin is a chemotherapeutic agent that kills fast dividing cells. Bevacizumab (Avastin) blocks blood vessel growth into the tumor thus cutting off its blood supply which a tumor needs to grow. Women who are HER2-positive continue to receive Herceptin. Patients with newly diagnosed and progressing brain metastases are eligible.

Lapatinib Ditosylate (Tykerb) and Capecitabine in Treating Patients with Stage IV Breast Cancer and Brain Metastases

This phase II trial is to see how well lapatinib works with capecitabine (Xeloda) for women with HER-2 positive brain mets that have not yet received any other treatment for brain metastases. This means no immediate radiation to the brain. The purpose of this trial is to see how well these two agents work before radiation and to see if radiation might not be necessary. To enroll women must not have brain metastases that can be removed by surgery and must have at least one brain metastasis that is greater than 10 mm in size.

High-Dose Methotrexate and Liposomal Cytarabine in Treating Patients With Central Nervous System (CNS) Metastases From Breast Cancer

This phase II trial is looking at how well high dose methotrexate works in combination with liposomal (gel-like delivery system) cytarabine in the treatment of brain metastases. Both drugs are chemotherapies that are delivered intrathecally. This means that an Ommaya resevoir (a plastic dome-like device) is inserted under the scalp on top of the head which allows the drugs to penetrate directly into the cerebrospinal fluid. Aside from a small hole, the skull is not opened. The trial will look at both the safety and efficacy of these drugs and the intrathecal delivery system. Both this procedure (intrathecal administration) and these drugs have been used in the past.

Brain Mets-Capecitabine (Xeloda) and WBRT

This is a phase II trial to determine how well the capecitabine (Xeloda) works given at the same time as whole brain radiation followed by capecitabine and sunitinib given after radiation. Sunitinib is a new drug that stops blood vessel growth to the tumor starving it of nutrients and blood that it needs to grow. Sunitinib has not been approved for the treatment of breast cancer though it has been approved for kidney cancer.

AZD2171 and Whole Brain Radiation Therapy in Patients With Brain Metastasis

This is a phase I study that is looking for the highest dose of AZD2171 that can be given safely with whole brain radiation for brain metastases. AZD2171 blocks blood vessel growth (angiogenesis) by inhibiting VEGF, a growth factor, which promotes blood vessel growth. It is hoped that this agent will starve the tumor of its blood supply safely with whole brain radiation for brain metastases. AZD2171 blocks blood vessel growth (angiogenesis) by inhibiting VEGF, a growth factor which promotes blood vessel growth. It is hoped that this agent will starve the tumor of its blood supply.

BBBD Followed by Methotrexate and Carboplatin with and without Trastuzumab (Herceptin) in Treating Women with Breast Cancer Spread to the Brain

A phase I/II study looking at the side effects and best dose of carboplatin and methotrexate with and without trastuzumab (Herceptin) after mannitol (type of sugar) is given to disrupt the blood brain barrier. It is hoped that the disruption of the blood brain barrier will allow higher doses of drug to enter into the brain making radiation unnecessary. Very little Herceptin penetrates into the brain without disruption of the blood brain barrier due to the size of the Herceptin molecules.

Capecitabine Concomitantly with Whole Brain Radiotherapy (WBRT) Followed by Capecitabine and Sunitinib for CNS Metastases in Breast Cancer

The purpose of this non-randomized Phase II clinical trial is to test the safety and efficacy of this combination. All participants will get radiation, capecitabine (Xeloda) and sunitinib (Sutent).

Lapatinib in Combination with Radiation Therapy in Patients with Brain Metastases from HER2-positive Breast Cancer

The purpose of this Phase I clinical trial is to determine the safety of combining lapatinib (Tykerb) with radiation in people with breast cancer that has spread to the brain. It is thought that lapatinib may make cancer cells in the brain more sensitive to radiation. Other studies show that lapatinib may help to shrink or stabilize breast cancer tumors both inside and outside the brain.

Epothilone B in Treating Patients with CNS Metastases from Breast Cancer

This phase II trial is studying how well a new experimental treatment known as epothilone B (patupilone) works in treating patients with CNS metastases from breast cancer that have recurred after whole brain radiation. Patupilone does cross the blood-brain barrier.

Irinotecan and Temozolomide in Treating Patients with Breast Cancer Who Have Received Previous Treatment for Brain Metastases

The purpose of this phase II trial is to study the side effects of irinotecan (Camptosar) and temozolomide (Temodar) and to see how well they work together as a treatment for previously treated brain metastases.

Lapatinib and Temozolomide for the Treatment of Progressive Brain Disease in HER-2 Positive Breast Cancer (LAPTEM)

The purpose of this Belgian phase I trial is to determine the proper dose of these drugs for women whose brain metastases have continued to grow after surgery or radiation. This study will also be looking at the effect of the drug combination of lapatinib (Tykerb) and temozolomide (Temodar) in reducing metastatic growth in the brain. It is for women with Her2 positive breast cancer.

Capecitabine, Cyclophosphamide, Doxorubicin, Gemcitabine, Lapatinib, Paclitaxel, Trastuzumab, or Vinorelbine in Treating Women with Brain Metastases from Breast Cancer

A study to see which chemotherapy agents penetrate the blood brain barrier and get into brain metastases.



Brain Metastases/CNS Trials, Including but not Limited to Breast Cancer
Safety Study of High Dose Temozolomide to Treat Relapsed/Refractory Central Nervous System (CNS) Malignancy (CN-306)

An Open-label, Phase I/IIa, Dose Escalating Study of 2B3-101 in Patients With Solid Tumors and Brain Metastases or Recurrent Malignant Glioma.

Perfexion Brain Metastasis

Stereotactic Radiosurgery With Sunitinib for Brain Metastases

Study of the Combination of Vorinostat and Radiation Therapy for the Treatment of Patients With Brain Metastases

Evaluation of [18F]-ML-10 as a PET Imaging Radiotracer for Early Detection of Response of Brain Metastases to Stereotactic Radio Surgery

Evaluation of the Efficacy and Safety of [18F]-ML-10, as a PET Imaging Radiotracer, in Early Detection of Response of Brain Metastases of Solid Tumors to Radiation Therapy

Whole-Brain Radiotherapy (WBRT) Versus WBRT and Integrated Boost Using Helical Tomotherapy for Multiple Brain Metastases

Volumetric Modulated Arc Therapy (VMAT) for Brain Metastases

AZD2171 and Whole Brain Radiation Therapy (WBRT) in Patients With Brain Metastases

131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiation in Patients With Multiple Brain Metastases From Solid Tumors

Dose Escalation/De-escalation Study of Pre-operative Stereotactic Radiosurgery for Brain Metastases(RAD 1002)

Stereotactic Radiosurgery in Treating Patients With Brain Metastases

Phase I/II Study of Fractionated Stereotactic Radiosurgery to Treat Large Brain Metastases

Recruiting Exclusive Hypofractionated Stereotactic Radiotherapy in Non-resectable Single Brain Metastasis

Combination of Sorafenib and Radiation for Brain Metastases and Primary Brain Tumors

Bendamustine and Radiation Therapy in Treating Patients With Brain Metastases Caused by Solid Tumors

Stereotactic Radiation Therapy in Treating Patients With Brain Metastases

Riluzole and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

Study Bendamustine Concurrent Whole Brain Radiation Brain Metastases From Solid Tumors

Dexamethasone for Palliation - Brain Metastases

Stereotactic Radiosurgery to the Resection Cavity Following Surgical Removal of Brain Metastasis

Neuropsychological Measures in Patients Undergoing Radiation Therapy for Brain Metastases

External-Beam Radiation Therapy With or Without Indinavir and Ritonavir in Treating Patients With Brain Metastases

Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

Stereotactic Radiation Therapy With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

A Trial of Postoperative Whole Brain Radiation Therapy vs. Salvage Stereotactic Radiosurgery Therapy for Metastasis

Exploring the Role of 3T MRI in Gamma Knife Radiosurgery

MRI Using Ferumoxytol in Patients With Primary Brain Cancer or Brain Metastases From Lung or Breast Cancer

Maximum Tolerated Dose (MTD) Finding Trial for Whole Brain Radiation Therapy (WBRT) Using RapidArc

Radiation Therapy in Treating Patients Who Are Undergoing Surgery to Remove a Metastatic Brain Tumor

Fluorescence Guided Resection of Brain Tumors

Resection Bed Post-Surgical Stereotactic Radiosurgery (SRS)

Cytochlor, Tetrahydrouridine, and External-Beam Radiation Therapy in Treating Patients With Cancer That Has Spread to the Brain

Predictive Value of Dynamic Contrast Enhancement MRI on a Cerebral Tumor Response to Gamma Knife Treatment

Recruiting Iodine I 131 Monoclonal Antibody 3F8 in Treating Patients With Central Nervous System Cancer or Leptomeningeal Cancer

Melphalan With BBBD in Treating Patients With Brain Malignancies

Photodynamic Therapy With Porfimer Sodium in Treating Patients With Refractory Brain Tumors

Temsirolimus With or Without Temozolomide in Treating Patients With Primary or Metastatic Brain Tumors

Donepezil in Treating Patients Who Have Undergone Radiation Therapy for Brain Tumors

Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

Magnetic Resonance Imaging-Guided Laser Induced Thermal Therapy for Treatment of Metastatic Brain Tumors

Safety Study of High Dose Temozolomide to Treat Relapsed/Refractory Central Nervous System (CNS) Malignancy

[Lani]

what the future may hold:
Pharm Res. 2012 Mar 8. [Epub ahead of print]
Treatment of Experimental Brain Metastasis with MTO-Liposomes: Impact of Fluidity and LRP-Targeting on the Therapeutic Result.
Orthmann A, Zeisig R, Süss R, Lorenz D, Lemm M, Fichtner I.
Source
Experimental Pharmacology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125, Berlin-Buch, Germany.
Abstract
PURPOSE:
To test targeted liposomes in an effort to improve drug transport across cellular barriers into the brain.
METHODS:
Therefore we prepared Mitoxantrone (MTO) entrapping, rigid and fluid liposomes, equipped with a 19-mer angiopeptide as ligand for LDL lipoprotein receptor related protein (LRP) targeting.
RESULTS:
Fluid, ligand bearing liposomes showed in vitro the highest cellular uptake and transcytosis and were significantly better than the corresponding ligand-free liposomes and rigid, ligand-bearing vesicles. Treatment of mice, transplanted with human breast cancer cells subcutaneously and into the brain, with fluid membrane liposomes resulted in a significant reduction in the tumor volume by more than 80% and in a clear reduction in drug toxicity. The improvement was mainly depended on liposome fluidity while the targeting contributed only to a minor degree. Pharmacokinetic parameters were also improved for liposomal MTO formulations in comparison to the free drug. So the area under the curve was increased and t(1/2) was extended for liposomes.
CONCLUSION:
Our data show that it is possible to significantly improve the therapy of brain metastases if MTO-encapsulating, fluid membrane liposomes are used instead of free MTO. This effect could be further enhanced by fluid, ligand bearing liposomes.
PMID: 22399388