HER2 Support Group Forums - View Single Post

Cindi · 01-06-2006, 07:01 AM

Lisa,

I are REALLY sorry to hear about the stinky news on your latest scans. I agree with the others on checking out Avastin, cisplatin. I had such confidence in my previous medical team... but looking back it was mainly in my Physician Asst. I just started a Lapatinib trial (about 1 1/2 week ago). They are hard trials to get into. The only one I fit was the refractory inflammatory one. I didn't start out with inflammatory BC at orginal DX, but it has remained in the skin since recurrence. Anyway, I am going to paste in the latest trial, the biggest "jump" is staying off all Chemo for 4 weeks. That was really scary for me and my mets aren't as advanced as yours. So, maybe this is too much of a leap for you, but as all the others have said, you are REALLY an inspiration to us all and we want to help you in anyway that we can.

God Bless,

Cindi.

P.S. There is the Angel network for flying and I am sure that somehow/somewhere you can get assitance for living expenses in Maryland. When I called Bethesda about another trial, they were VERY sharp. I am talking about the second person (the one that calls you back within 1-2 days).

P.S.S. I'll be Praying for you !!!!!!!!!!!!!!!!

A Phase II Study to Evaluate the Efficacy and Safety Using Combined Monoclonal Antibodies, Trastuzumab and Pertuzumab in Subjects with HER-2 Overexpressed Locally Advanced and Metastatic Breast Cancer

This study is currently recruiting patients.
Verified by National Institutes of Health Clinical Center (CC) November 22, 2005

Sponsored by:National Cancer Institute (NCI)Information provided by:National Institutes of Health Clinical Center (CC)ClinicalTrials.gov Identifier:NCT00263224

Purpose

The HER-2 transmembrane ligand-less tyrosine kinase receptor has become a popular molecular target in the treatment of cancer in recent years. It is overexpressed in 25-30% of breast cancers. Recombinant monoclonal antibodies, trastuzumab and pertuzumab, both target the HER-2 receptor but at different epitopes of its extracellular domain. Trastuzumab exerts its anti-tumor activity by several mechanisms; these include receptor down modulation, prevention of cleavage of the receptor's extracellular domain and by recruiting host immune effector cells. Pertuzumab sterically disrupts HER-2 heterodimerization with other HER family members, thus preventing lateral signal transduction via the Ras-Raf-MAPK and the P-13K-Akt pathways. As the majority of breast tumors that initially respond to trastuzumab begin to progress within 9 months, treatment with this monoclonal antibody combination may be beneficial.
The purpose of this study is to determine the efficacy and safety of pertuzumab and trastuzumab in patients with HER-2 overexpressed locally advanced and metastatic breast cancer that have previously been treated with trastuzumab-based therapy. Before commencing treatment, all eligible patients will have a cardiology review and serum samples taken for correlative studies. Additionally, eligible patients with tumor accessible to biopsy will have biopsies performed.
On Day 1, an intravenous dose of trastuzumab will be administered. If patients have not received trastuzumab in over 1 month, they will receive a loading dose of 8mg/kg. If they have received trastuzumab within 1 month, an intravenous maintenance dose of 6mg/kg will be administered. On Day 2, an intravenous loading dose of pertuzumab (840mg) will be administered. On Day 22, an intravenous maintenance dose of both agents will be given (6mg/kg of trastuzumab and 420mg of pertuzumab). Within three days before receiving treatment on Day 22, a repeat cardiology evaluation will be completed on all patients and tumor biopsies performed on those who underwent biopsy before Day 1.
Both agents will be administered every 3 weeks from then on until disease progression occurs or drug toxicity precludes further treatment. Subjects will be evaluated clinically with physical examination and laboratory assessments every three weeks throughout the study. Subjects will be formally evaluated for cardiotoxicity using quantitative echocardiography before every cycle (or every 3 weeks) or at any point if there is clinical indication. Measurable disease will be re-assessed every 6 weeks (or after every 2 cycles). Exploratory correlative studies investigating downstream signaling markers of HER-2 receptor will be completed on both tissue and blood samples.
InterventionPhase Drug: Pertuzumab
Phase II

MedlinePlus consumer health information

Study Type: Interventional
Study Design: Treatment, Safety/Efficacy

Further study details as provided by National Institutes of Health Clinical Center (CC):

Expected Total Enrollment: 40
Study start: December 2, 2005

The HER-2 transmembrane ligand-less tyrosine kinase receptor has become a popular molecular target in the treatment of cancer in recent years. It is overexpressed in 25-30% of breast cancers. Recombinant monoclonal antibodies, trastuzumab and pertuzumab, both target the HER-2 receptor but at different epitopes of its extracellular domain. Trastuzumab exerts its anti-tumor activity by several mechanisms; these include receptor downmodulation, prevention of cleavage of the receptor's extracellular domain and by recruiting host immune effector cells. Pertuzumab sterically disrupts HER-2 heterodimerization with other HER family members, thus preventing lateral signal transduction via the Ras-Raf-MAPK and the P-13K-Akt pathways. As the majority of breast tumors that initially respond to trastuzumab begin to progress within 9 months, treatment with this monoclonal antibody combination may be beneficial.
The purpose of this study is to determine the efficacy and safety of pertuzumab and trastuzumab in patients with HER-2 overexpressed locally advanced and metastatic breast cancer that have previously been treated with trastuzumab-based therapy. Before commencing treatment, all eligible patients will have a cardiology review and serum samples taken for correlative studies. Additionally, eligible patients with tumor accessible to biopsy will have biopsies performed.
On Day 1, an intravenous dose of trastuzumab will be administered. If patients have not received trastuzumab in over 1 month, they will receive a loading dose of 8mg/kg. If they have received trastuzumab within 1 month, an intravenous maintenance dose of 6mg/kg will be administered. On Day 2, an intravenous loading dose of pertuzumab (840mg) will be administered. On Day 22, an intravenous maintenance dose of both agents will be given (6mg/kg of trastuzumab and 420mg of pertuzumab). Within three days before receiving treatment on Day 22, a repeat cardiology evaluation will be completed on all patients and tumor biopsies performed on those who underwent biopsy before Day 1.
Both agents will be administered every 3 weeks from then on until disease progression occurs or drug toxicity precludes further treatment. Subjects will be evaluated clinically with physical examination and laboratory assessments every three weeks throughout the study. Subjects will be formally evaluated for cardiotoxicity using quantitative echocardiography before every cycle (or every 3 weeks) or at any point if there is clinical indication. Measurable disease will be re-assessed every 6 weeks (or after every 2 cycles). Exploratory correlative studies investigating downstream signaling markers of HER-2 receptor will be completed on both tissue and blood samples.

Eligibility

Genders Eligible for Study: Both
Criteria
INCLUSION CRITERIA:
1. All patients must have histologically documented HER-2 overexpressed invasive carcinoma consistent with breast cancer confirmed by immunohistochemistry (3+) or gene amplification by fluorescence in-situ hybridization (FISH).
2. Patients with locally advanced breast cancer that is inoperable having experienced disease progression despite receiving neoadjuvant chemotherapy. Patients must also have progressed on or after trastuzumab based therapy. Patients may have received 1-3 prior trastuzumab-based treatments in the treatment of their disease.
3. Patients with metastatic breast cancer that have progressed on or after trastuzumab-based therapy. Patients may have received 1-3 prior trastuzumab-based treatment.
4. Patients must be able to provide informed consent.
5. Patients must be aged greater than or equal to 18 years of age.
6. Patients must have measurable disease with at least one lesion that can be accurately measured in at least one dimension.
7. Patients must have recovered from reversible acute effects of prior chemotherapy regimens or radiotherapy to NCI-CTC grade less than or equal to 1 (excluding alopecia).
8. ECOG performance status of 0 or 1 (See Appendix A).
9. Patients must have a left ventricular ejection fraction above the lower limit of normal without clinical signs or symptoms of heart failure, and without recorded significant cardiac event to date.
10. Women of childbearing potential must agree to use an accepted and effective method of contraception during their participation on the trial.
11. Patients must have adequate bone marrow, hepatic and renal function as defined by the following:
- Absolute neutrophil count greater than or equal to 1500/microliter, - Platelet count greater than or equal to 75,000/ l, and
- Serum creatinine less than or equal to 1.5 x ULN
- Serum bilirubin less than or equal to 1.5x the upper limit of normal (ULN) and alkaline phosphatase, AST, and ALT less than or equal to 2.5x ULN (ALT, AST and alkaline phosphatase less than or equal to 5x ULN for subjects with liver metastases).
EXCLUSION CRITERIA:
1. Patients with locally advanced breast cancer who have not received chemotherapy.
2. Patients must not have received treatment with other experimental anti-cancer agents within 3 weeks of starting the study drug combination.
3. Patients must not have received chemotherapy, radiotherapy (other than a short course of palliative radiotherapy for bone pain) or immunotherapy within 4 weeks of Day 1 treatment (with the exception of nitrosureas or mitomycin for which 6 weeks must have passed).
4. Patients must not have oral hormonal therapy within 2 weeks of Day 1 treatment. Fulvestrant must not have been administered within 4 weeks of Day 1 treatment.
5. Present clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan. A patient with brain and/or leptomeningeal metastases may be included only if he/she has stable lesions following standard treatment (surgery or radiation), is asymptomatic on neurological examination, is not receiving corticosteroid therapy to control symptoms.
6. Patients must not have an ejection fraction, determined by quantitative echocardiogram or MRI of heart below the lower limit of normal.
7. Patients with uncontrolled hypertension (sustained systolic blood pressure greater than 180mmHg or diastolic blood pressure greater than 100mmHg), significant valvular disease (aortic or mitral regurgitation of 3 or 4+/ 4+ severity or stenosis of either valve), history of uncontrolled cardiac arrhythmias, prior symptomatic or asymptomatic myocardial infarction or angina pectoris requiring anti-anginal medication, poorly controlled diabetes mellitus (fasting blood sugar greater than 200mg/dL).
8. Prior exposure of greater than 360mg/m(2) doxorubicin or liposomal doxorubicin, greater than 120mg/m(2) mitoxantrone, greater than 600mg/m(2) epirubicin or 90mg/m(2) idarubicin.
9. Patients whom have been prohibited from further trastuzumab use in the past due to hypersensitivity reaction.
10. Patients with acquired immunodeficiency syndrome.
11. Serious intercurrent medical illness or subjects on the equivalence of or greater than 20mg prednisone for non-malignant conditions.
12. Pregnant or lactating women.
13. Patients must not have had an active malignancy other than breast cancer, in-situ carcinoma of the cervix or non-melanomatous skin cancers in the past 5 years.
14. Ongoing liver disease, including viral or other hepatitis, current alcohol abuse or cirrhosis.
15. Inability to comply with study and follow-up procedures.
16. Any patient may be excluded from this study at the discretion of the principal investigator if it is deemed that their participation would represent an unacceptable medical or psychiatric risk.

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00263224

Maryland
National Cancer Institute (NCI), 9000 Rockville Pike, Bethesda, Maryland, 20892, United States; Recruiting Patient Recruitment and Public Liaison Office 1-800-411-1222 prpl@mail.cc.nih.gov
TTY 1-866-411-1010

01-06-2006, 07:01 AM	#22
Cindi Senior Member Join Date: Oct 2005 Posts: 50	This SUCKS! Lisa, I are REALLY sorry to hear about the stinky news on your latest scans. I agree with the others on checking out Avastin, cisplatin. I had such confidence in my previous medical team... but looking back it was mainly in my Physician Asst. I just started a Lapatinib trial (about 1 1/2 week ago). They are hard trials to get into. The only one I fit was the refractory inflammatory one. I didn't start out with inflammatory BC at orginal DX, but it has remained in the skin since recurrence. Anyway, I am going to paste in the latest trial, the biggest "jump" is staying off all Chemo for 4 weeks. That was really scary for me and my mets aren't as advanced as yours. So, maybe this is too much of a leap for you, but as all the others have said, you are REALLY an inspiration to us all and we want to help you in anyway that we can. God Bless, Cindi. P.S. There is the Angel network for flying and I am sure that somehow/somewhere you can get assitance for living expenses in Maryland. When I called Bethesda about another trial, they were VERY sharp. I am talking about the second person (the one that calls you back within 1-2 days). P.S.S. I'll be Praying for you !!!!!!!!!!!!!!!! A Phase II Study to Evaluate the Efficacy and Safety Using Combined Monoclonal Antibodies, Trastuzumab and Pertuzumab in Subjects with HER-2 Overexpressed Locally Advanced and Metastatic Breast Cancer This study is currently recruiting patients. Verified by National Institutes of Health Clinical Center (CC) November 22, 2005 Sponsored by:National Cancer Institute (NCI)Information provided by:National Institutes of Health Clinical Center (CC)ClinicalTrials.gov Identifier:NCT00263224 Purpose The HER-2 transmembrane ligand-less tyrosine kinase receptor has become a popular molecular target in the treatment of cancer in recent years. It is overexpressed in 25-30% of breast cancers. Recombinant monoclonal antibodies, trastuzumab and pertuzumab, both target the HER-2 receptor but at different epitopes of its extracellular domain. Trastuzumab exerts its anti-tumor activity by several mechanisms; these include receptor down modulation, prevention of cleavage of the receptor's extracellular domain and by recruiting host immune effector cells. Pertuzumab sterically disrupts HER-2 heterodimerization with other HER family members, thus preventing lateral signal transduction via the Ras-Raf-MAPK and the P-13K-Akt pathways. As the majority of breast tumors that initially respond to trastuzumab begin to progress within 9 months, treatment with this monoclonal antibody combination may be beneficial. The purpose of this study is to determine the efficacy and safety of pertuzumab and trastuzumab in patients with HER-2 overexpressed locally advanced and metastatic breast cancer that have previously been treated with trastuzumab-based therapy. Before commencing treatment, all eligible patients will have a cardiology review and serum samples taken for correlative studies. Additionally, eligible patients with tumor accessible to biopsy will have biopsies performed. On Day 1, an intravenous dose of trastuzumab will be administered. If patients have not received trastuzumab in over 1 month, they will receive a loading dose of 8mg/kg. If they have received trastuzumab within 1 month, an intravenous maintenance dose of 6mg/kg will be administered. On Day 2, an intravenous loading dose of pertuzumab (840mg) will be administered. On Day 22, an intravenous maintenance dose of both agents will be given (6mg/kg of trastuzumab and 420mg of pertuzumab). Within three days before receiving treatment on Day 22, a repeat cardiology evaluation will be completed on all patients and tumor biopsies performed on those who underwent biopsy before Day 1. Both agents will be administered every 3 weeks from then on until disease progression occurs or drug toxicity precludes further treatment. Subjects will be evaluated clinically with physical examination and laboratory assessments every three weeks throughout the study. Subjects will be formally evaluated for cardiotoxicity using quantitative echocardiography before every cycle (or every 3 weeks) or at any point if there is clinical indication. Measurable disease will be re-assessed every 6 weeks (or after every 2 cycles). Exploratory correlative studies investigating downstream signaling markers of HER-2 receptor will be completed on both tissue and blood samples. InterventionPhase Drug: Pertuzumab Phase II MedlinePlus consumer health information Study Type: Interventional Study Design: Treatment, Safety/Efficacy Further study details as provided by National Institutes of Health Clinical Center (CC): Expected Total Enrollment: 40 Study start: December 2, 2005 The HER-2 transmembrane ligand-less tyrosine kinase receptor has become a popular molecular target in the treatment of cancer in recent years. It is overexpressed in 25-30% of breast cancers. Recombinant monoclonal antibodies, trastuzumab and pertuzumab, both target the HER-2 receptor but at different epitopes of its extracellular domain. Trastuzumab exerts its anti-tumor activity by several mechanisms; these include receptor downmodulation, prevention of cleavage of the receptor's extracellular domain and by recruiting host immune effector cells. Pertuzumab sterically disrupts HER-2 heterodimerization with other HER family members, thus preventing lateral signal transduction via the Ras-Raf-MAPK and the P-13K-Akt pathways. As the majority of breast tumors that initially respond to trastuzumab begin to progress within 9 months, treatment with this monoclonal antibody combination may be beneficial. The purpose of this study is to determine the efficacy and safety of pertuzumab and trastuzumab in patients with HER-2 overexpressed locally advanced and metastatic breast cancer that have previously been treated with trastuzumab-based therapy. Before commencing treatment, all eligible patients will have a cardiology review and serum samples taken for correlative studies. Additionally, eligible patients with tumor accessible to biopsy will have biopsies performed. On Day 1, an intravenous dose of trastuzumab will be administered. If patients have not received trastuzumab in over 1 month, they will receive a loading dose of 8mg/kg. If they have received trastuzumab within 1 month, an intravenous maintenance dose of 6mg/kg will be administered. On Day 2, an intravenous loading dose of pertuzumab (840mg) will be administered. On Day 22, an intravenous maintenance dose of both agents will be given (6mg/kg of trastuzumab and 420mg of pertuzumab). Within three days before receiving treatment on Day 22, a repeat cardiology evaluation will be completed on all patients and tumor biopsies performed on those who underwent biopsy before Day 1. Both agents will be administered every 3 weeks from then on until disease progression occurs or drug toxicity precludes further treatment. Subjects will be evaluated clinically with physical examination and laboratory assessments every three weeks throughout the study. Subjects will be formally evaluated for cardiotoxicity using quantitative echocardiography before every cycle (or every 3 weeks) or at any point if there is clinical indication. Measurable disease will be re-assessed every 6 weeks (or after every 2 cycles). Exploratory correlative studies investigating downstream signaling markers of HER-2 receptor will be completed on both tissue and blood samples. Eligibility Genders Eligible for Study: Both Criteria INCLUSION CRITERIA: 1. All patients must have histologically documented HER-2 overexpressed invasive carcinoma consistent with breast cancer confirmed by immunohistochemistry (3+) or gene amplification by fluorescence in-situ hybridization (FISH). 2. Patients with locally advanced breast cancer that is inoperable having experienced disease progression despite receiving neoadjuvant chemotherapy. Patients must also have progressed on or after trastuzumab based therapy. Patients may have received 1-3 prior trastuzumab-based treatments in the treatment of their disease. 3. Patients with metastatic breast cancer that have progressed on or after trastuzumab-based therapy. Patients may have received 1-3 prior trastuzumab-based treatment. 4. Patients must be able to provide informed consent. 5. Patients must be aged greater than or equal to 18 years of age. 6. Patients must have measurable disease with at least one lesion that can be accurately measured in at least one dimension. 7. Patients must have recovered from reversible acute effects of prior chemotherapy regimens or radiotherapy to NCI-CTC grade less than or equal to 1 (excluding alopecia). 8. ECOG performance status of 0 or 1 (See Appendix A). 9. Patients must have a left ventricular ejection fraction above the lower limit of normal without clinical signs or symptoms of heart failure, and without recorded significant cardiac event to date. 10. Women of childbearing potential must agree to use an accepted and effective method of contraception during their participation on the trial. 11. Patients must have adequate bone marrow, hepatic and renal function as defined by the following: - Absolute neutrophil count greater than or equal to 1500/microliter, - Platelet count greater than or equal to 75,000/ l, and - Serum creatinine less than or equal to 1.5 x ULN - Serum bilirubin less than or equal to 1.5x the upper limit of normal (ULN) and alkaline phosphatase, AST, and ALT less than or equal to 2.5x ULN (ALT, AST and alkaline phosphatase less than or equal to 5x ULN for subjects with liver metastases). EXCLUSION CRITERIA: 1. Patients with locally advanced breast cancer who have not received chemotherapy. 2. Patients must not have received treatment with other experimental anti-cancer agents within 3 weeks of starting the study drug combination. 3. Patients must not have received chemotherapy, radiotherapy (other than a short course of palliative radiotherapy for bone pain) or immunotherapy within 4 weeks of Day 1 treatment (with the exception of nitrosureas or mitomycin for which 6 weeks must have passed). 4. Patients must not have oral hormonal therapy within 2 weeks of Day 1 treatment. Fulvestrant must not have been administered within 4 weeks of Day 1 treatment. 5. Present clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by CT or MRI brain scan. A patient with brain and/or leptomeningeal metastases may be included only if he/she has stable lesions following standard treatment (surgery or radiation), is asymptomatic on neurological examination, is not receiving corticosteroid therapy to control symptoms. 6. Patients must not have an ejection fraction, determined by quantitative echocardiogram or MRI of heart below the lower limit of normal. 7. Patients with uncontrolled hypertension (sustained systolic blood pressure greater than 180mmHg or diastolic blood pressure greater than 100mmHg), significant valvular disease (aortic or mitral regurgitation of 3 or 4+/ 4+ severity or stenosis of either valve), history of uncontrolled cardiac arrhythmias, prior symptomatic or asymptomatic myocardial infarction or angina pectoris requiring anti-anginal medication, poorly controlled diabetes mellitus (fasting blood sugar greater than 200mg/dL). 8. Prior exposure of greater than 360mg/m(2) doxorubicin or liposomal doxorubicin, greater than 120mg/m(2) mitoxantrone, greater than 600mg/m(2) epirubicin or 90mg/m(2) idarubicin. 9. Patients whom have been prohibited from further trastuzumab use in the past due to hypersensitivity reaction. 10. Patients with acquired immunodeficiency syndrome. 11. Serious intercurrent medical illness or subjects on the equivalence of or greater than 20mg prednisone for non-malignant conditions. 12. Pregnant or lactating women. 13. Patients must not have had an active malignancy other than breast cancer, in-situ carcinoma of the cervix or non-melanomatous skin cancers in the past 5 years. 14. Ongoing liver disease, including viral or other hepatitis, current alcohol abuse or cirrhosis. 15. Inability to comply with study and follow-up procedures. 16. Any patient may be excluded from this study at the discretion of the principal investigator if it is deemed that their participation would represent an unacceptable medical or psychiatric risk. Location and Contact Information Please refer to this study by ClinicalTrials.gov identifier NCT00263224 Maryland National Cancer Institute (NCI), 9000 Rockville Pike, Bethesda, Maryland, 20892, United States; Recruiting Patient Recruitment and Public Liaison Office 1-800-411-1222 prpl@mail.cc.nih.gov TTY 1-866-411-1010