Phase II Study of Eribulin Mesylate, Trastuzumab, and Pertuzumab in Women With Metastatic, Unresectable Locally Advanced, or Locally Recurrent HER2-Positive Breast Cancer
|First Received Date ICMJE||July 24, 2013|
|Last Updated Date||May 4, 2016|
|Start Date ICMJE||August 2013|
|Estimated Primary Completion Date||May 2017 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01912963 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE
|Original Other Outcome Measures ICMJE||Same as current|
|Brief Title ICMJE||Phase II Study of Eribulin Mesylate, Trastuzumab, and Pertuzumab in Women With Metastatic, Unresectable Locally Advanced, or Locally Recurrent HER2-Positive Breast Cancer|
|Official Title ICMJE||A Phase II Study of Eribulin Mesylate in Combination With Trastuzumab and Pertuzumab in Women With Metastatic, Unresectable Locally Advanced, or Locally Recurrent Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer|
In this study, the investigators are testing the effectiveness of the combination of eribulin, pertuzumab and trastuzumab to learn whether this combination of drugs works in treating advanced HER2-positive breast cancer that had received at least one prior treatment previously. At this point, the standard treatment for HER2-positive cancer that has progressed (grown) after a first treatment is chemotherapy combined with therapies that target the HER2 protein (e.g., trastuzumab or lapatinib).
All of the medications that are being tested in this study are approved by the Food and Drug administration (FDA) for the treatment of metastatic breast cancer. However, the combination of these three medications in participants has not yet been tested. Eribulin is a chemotherapy agent that is approved for the treatment of metastatic breast cancer for women who have previously received at least two prior chemotherapeutic regimens for the treatment of their metastatic disease. Pertuzumab and trastuzumab are also both approved for the treatment of advanced HER2-positive breast cancer. Both agents help treat breast cancer by binding HER2 receptor. However, pertuzumab and trastuzumab bind to different parts of the HER2 receptor.
The goal of this research study is to find out if adding pertuzumab, trastuzumab and eribulin is effective in treating women with metastatic, HER2-positive breast cancer. The Investigators, will also gather more information on the side effects of these treatments
The investigators also plan to gather genetic information from participants' tumors (collected at biopsies). Cancers occur when the molecules that control normal cell growth (genes and proteins) are altered. Changes in the tumor genes and in the genes of normal cells are called "alterations." Many of these alterations can be detected by directly examining cancer cells in a tumor or circulating in blood. Several alterations that occur repeatedly in certain types of cancers have already been identified. These discoveries have led to the development of new drugs that "target" those alterations. More remain to be discovered.
Some of the alterations are found in genes. Genes are composed of DNA "letters," which contain the instructions that tell the cells in our bodies how to grow and work. Genes make proteins which actually carry out the instructions in our cells.
The investigator would like to use your DNA to look for alterations in the genes in cancer cells and blood cells using a technology called "sequencing." Gene sequencing is a way of reading the DNA to identify errors in genes that may contribute to the behavior of cells. Some changes in genes occur only in cancer cells. Others occur in normal cells as well, in the genes that may have been passed from parent to child. This research study will examine both kinds of genes.
One of the scientific goals of this research study is to perform gene sequencing (gene tests) on your cancer cells (obtained from biopsies or surgery) and normal tissues (usually blood). The results of the gene tests will be used to try to develop better ways to treat and prevent cancers. As part of this work, we may also learn things about the genes in your normal cells. However, because interpretation of these tests will require further study,the investigator will not disclose these results to participants who participate on this component of the study.
Each study treatment cycle lasts 21 days (3 weeks). The patients will receive eribulin on the first day (day 1) and on the 8th day (day 8) of the cycle. The patients will also receive trastuzumab and pertuzumab on day 1. All drugs will be given intravenously.
The dose of pertuzumab and trastuzumab will be the same for all patients on study, and will be the standard approved dose for each of these medications.
In the first portion of the study, the investigators will examine which dose of eribulin is the safest when given in combination with pertuzumab and trastuzumab. For the first 6 participants enrolled onto the study,the investigators will be looking to see if the standard dose of eribulin can be administered safely with standard doses pertuzumab and trastuzumab. If this dose of eribulin is not tolerated well, the investigator will test the three-medication combination with a lower dose of eribulin. The highest dose that will be found to be safe will be used in the next participants. The dose the patients receive will depend on the number of participants who have been enrolled in the study before and how well they have tolerated their doses.
At the start of each cycle the patients will have:
Additional research procedures to be performed:
One of the main reasons to study the genetic characteristics of cancers is to learn whether they can predict response to existing treatments. Therefore, in this study, the investigators would also link the results of the gene tests on the patient's cancer with medical information that has been generated during the course of the patient's study treatment. The medical information required for this part of the study will be gathered from the patient's medical record. Some of the patients specimens, as well as some of the material generated during the analysis of the patient's tissues or blood, may be useful for study in the future, with newer technologies and approaches. The investigators are asking the patient's permission to store these specimens and materials in a secure biological sample storage facility for possible later research.
Finally, rapid progress in understanding and treating cancer will occur when some of the genetic information derived from the patient's tissues and blood can be shared with other researchers. In particular, the National Institutes of Health (NIH) and other organizations have developed special data (information) repositories that analyze data and collect the results of certain types of genetic studies. These central banks will store the patient's genetic information, samples, and survey/interview information and provide them to qualified researchers to do more studies. Therefore, the Investigators are also asking the patient's permission to share their results with these special banks.
After the final dose of the study drug:
The patient will have a follow-up visit one month after coming off study treatment every 9 weeks. During that visit, the patient will have a physical examination, functional assessment, assessment of any side effect and current medications. If the patient continues to have ongoing side effects related to the study treatment, the investigator will continue to follow the patient until these side effects resolve. If the patient withdraws from the study for another reason other than tumor progression, the patient will continue to be followed until tumor progression.
In addition, the investigator will collect about 5-6 additional tablespoons of blood for research and to measure if a marker for particular breast cancer exists. The patient also will be asked to perform another tumor biopsy for research purposes.
The investigator would like to keep track of the patient's medical condition for the rest of their life. The investigator would like to do this by calling the patient on the telephone once a year to see how they are doing. Keeping in touch with the patient and checking the condition every year helps the investigator look at the long-term effects of the research study. This is an optional procedure.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||HER-2 Positive Breast Cancer|
|Intervention ICMJE||Drug: Pertuzumab, Trastuzumab and Eribulin
Each study treatment cycle lasts 21 days. The patient will receive eribulin on the first day (day 1) and on the 8th day (day 8) of the cycle. The patient will also receive trastuzumab and pertuzumab on day 1. All drugs will be given to intravenously in clinic.
In the first portion of the study, we will examine which dose of eribulin is the safest when given in combination with pertuzumab and trastuzumab. For the first 6 participants enrolled onto the study, we will be look to see if the standard dose of eribulin can be administered safely with standard doses pertuzumab and trastuzumab. If this dose of eribulin is not tolerated well, we will test the three-medication combination with a lower dose of eribulin. The highest dose that will be found to be safe will be used in the next participants. The dose you receive will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their doses.
|Study Arm (s)||Experimental: Pertuzumab, Trastuzumab and Eribulin
To evaluate the activity of trastuzumab and pertuzumab in combination with eribulin mesylate in women with metastatic or locally recurrent HER2-positive breast cancer that are refractory to trastuzumab-containing regimens.There will be a safety run-in prior to the start of the Phase II study. Each study treatment cycle lasts 21 days (3 weeks). The patient will receive eribulin on the first day (day 1) and on the 8th day (day 8) of the cycle. The patient will also receive trastuzumab and pertuzumab on day 1. All drugs will be given to the patient intravenously in clinic. The dose of pertuzumab and trastuzumab will be the same for everyone on study, and will be the standard approved dose for each of these medications.
Intervention: Drug: Pertuzumab, Trastuzumab and Eribulin
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||81|
|Estimated Completion Date||January 2021|
|Estimated Primary Completion Date||May 2017 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- Participants must have invasive primary tumor or metastatic tissue confirmation of HER2-positive status, defined as presence of one or more of the following criteria: Over-expression by IHC with score of 3+ AND/OR HER2 gene amplification (> 6 HER2 gene copies per nucleus or a FISH ratio [HER2 gene copies to chromosome 17 signals] of ≥ 2.0) Note: Participants with a negative or equivocal overall result (FISH ratio of <2.0 or ≤ 6.0 HER2 gene copies per nucleus) and IHC staining scores of 0, 1+, 2+ are not eligible for enrollment.
Exclusion Criteria: - Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01912963|
|Other Study ID Numbers ICMJE||13-163|
|Has Data Monitoring Committee||Yes|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Rachel Freedman, Dana-Farber Cancer Institute|
|Study Sponsor ICMJE||Dana-Farber Cancer Institute|
|Information Provided By||Dana-Farber Cancer Institute|
|Verification Date||May 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP