Cisplatin vs Paclitaxel for Triple Neg BRCA

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Dana-Farber Cancer Institute
Sponsor:
Collaborator:
Myriad Genetics
Information provided by (Responsible Party):
Erica Mayer, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01982448
First received: October 28, 2013
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

This research study is evaluating how well triple negative breast cancer responds to preoperative treatment with Cisplatin or Paclitaxel chemotherapy, and if use of a research test Homologous Recombination Deficiency (HRD) assay can predict response to preoperative treatment.


Condition Intervention Phase
Triple Negative Breast Cancer
Drug: Cisplatin
Drug: Paclitaxel
Procedure: Pre- and Post-chemotherapy clinical diagnostic tissue
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Preoperative Cisplatin Versus Paclitaxel in Patients With Triple Negative Breast Cancer Without Germline BRCA Mutations: Evaluating the Homologous Recombination Deficiency (HRD) Biomarker

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Correlation between HRD biomarker and pathologic response to pre-operative Cisplatin [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Correlation between HRD biomarker and pathologic response to pre-operative Cisplatin

  • Correlation between HRD Biomarker and pathologic response to pre-operative paclitaxel. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Correlation between HRD Biomarker and pathologic response to pre-operative paclitaxel.


Secondary Outcome Measures:
  • Comparison between HRD score predicting response for cisplatin versus paclitaxel [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Comparison between HRD score predicting response for cisplatin versus paclitaxel

  • Correlation between HRD biomarker and pathologic complete response to neoadjuvant cisplatin [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Correlation between HRD biomarker and pathologic complete response to neoadjuvant cisplatin

  • Correlation between HRD Biomarker score and pathologic complete response to paclitaxel. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Correlation between HRD Biomarker score and pathologic complete response to paclitaxel.

  • Correlation between HRD biomarker score and clinical response to pre-operative cisplatin. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Correlation between HRD biomarker score and clinical response to pre-operative cisplatin.

  • Correlation between HRD biomarker score and clinical response to preoperative paclitaxel [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Correlation between HRD biomarker score and clinical response to preoperative paclitaxel


Estimated Enrollment: 160
Study Start Date: February 2014
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paclitaxel

- Paclitaxel will be given as an IV infusion at a dose of 80mg/m2 weekly x 12 weeks (4 cycles).

Pre- and Post-chemotherapy clinical diagnostic tissue

  • The FFPE tumor block or unstained tissue sections from the clinical diagnostic pre-treatment core biopsy is mandatory.
  • A representative H&E stained slide from each block and the immunostained slides of the pre-treatment diagnostic core biopsy and an H&E slide of every block from the post-treatment surgical breast excision and axillary surgery specimens will be required.
  • A single representative FFPE block of residual tumor tissue obtained at the time surgery and a representative block of normal tissue is requested for banking and future research studies.
  • Research breast core biopsies of the target lesion will be obtained from all participants' prior to initiating protocol chemotherapy. These research biopsies are mandatory.
Drug: Paclitaxel
80mg/m2 weekly x 12 weeks (4 cycles).
Other Name: Taxol (NSC 125973)
Procedure: Pre- and Post-chemotherapy clinical diagnostic tissue

Pre- and Post-chemotherapy clinical diagnostic tissue The FFPE tumor block or minimum of 5 7-micron unstained tissue sections from the clinical diagnostic pre-treatment core biopsy is mandatory; this will be the source of tumor for the HRD assay.

Research breast core biopsies of the target lesion will be obtained from all participants' prior to initiating protocol chemotherapy. These research biopsies are mandatory. It is strongly recommended that core biopsies be image-guided. A clip should be placed in the target lesion at the time of diagnostic biopsy. If it was not, a clip should be placed at the time of the pre-chemotherapy research biopsy.

An acceptable research core biopsy is defined as a biopsy performed with a needle that is at least 14 gauge, preferably 11 gauge, with a minimum core length of 6 mm. If any of the required cores are less than 6 mm, additional core biopsies should be obtained. This information should be communicated to the operator performing the biopsy.

Experimental: Cisplatin

-Cisplatin will be given by IV at 75 mg/m2 every 3 weeks, 4 cycles. Pre- and Post-chemotherapy clinical diagnostic tissue

  • The FFPE tumor block or minimum of 5 7-micron unstained tissue sections from the clinical diagnostic pre-treatment core biopsy is mandatory
  • A representative H&E stained slide from each block and the immunostained slides of the pre-treatment diagnostic core biopsy and an H&E slide of every block from the post-treatment surgical breast excision and axillary surgery specimens will be required.
  • A single representative FFPE block of residual tumor tissue obtained at the time surgery after protocol treatment and a representative block of normal tissue is requested for banking and future research studies.
  • Research breast core biopsies of the target lesion will be obtained from all participants' prior to initiating protocol chemotherapy. These research biopsies are mandatory.
Drug: Cisplatin
75 mg/m2 IV q 3 weeks x 4 cycles
Other Name: Platinol ®-AQ
Procedure: Pre- and Post-chemotherapy clinical diagnostic tissue

Pre- and Post-chemotherapy clinical diagnostic tissue The FFPE tumor block or minimum of 5 7-micron unstained tissue sections from the clinical diagnostic pre-treatment core biopsy is mandatory; this will be the source of tumor for the HRD assay.

Research breast core biopsies of the target lesion will be obtained from all participants' prior to initiating protocol chemotherapy. These research biopsies are mandatory. It is strongly recommended that core biopsies be image-guided. A clip should be placed in the target lesion at the time of diagnostic biopsy. If it was not, a clip should be placed at the time of the pre-chemotherapy research biopsy.

An acceptable research core biopsy is defined as a biopsy performed with a needle that is at least 14 gauge, preferably 11 gauge, with a minimum core length of 6 mm. If any of the required cores are less than 6 mm, additional core biopsies should be obtained. This information should be communicated to the operator performing the biopsy.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must meet the following criteria on screening examination to be eligible to participate in the study
  • Pathologic documentation of invasive breast cancer by biopsy (FNA alone is not adequate).
  • AJCC clinical stage I with T1 > 1.5 cm, stage II or III invasive breast cancer.
  • Participants with multicentric or bilateral disease are eligible if at least one lesion meets stage eligibility criteria for the study and no tumor is HER2-positive. In this circumstance, the investigator must determine which will represent the target lesion to be assessed for response. This should remain consistent throughout the study. The target lesion should be selected on the basis of its size (lesion with the longest diameter) and suitability for accurate repetitive measurements.
  • Tumors must be HER2 negative defined as HER2 0 or 1+ by immunohistochemistry (IHC) assays and /or lack of gene amplification by FISH defined as a ratio < 2 on invasive tumor by local review.
  • ER and PgR status by IHC must be known. Tumor must be ER and PR negative (<1% staining) by local review.
  • Participant should have negative germline testing for BRCA1/2 gene mutations. Subjects who are considered otherwise eligible for the trial will have BRCA1/2 testing performed on an expedited basis as part of screening. If a potential subject does not have insurance coverage for testing or if results from available testing options will not be ready in time for enrollment in the study, costs for this test will be covered by the study. This form may also be used for genetic testing which will be covered by the participant's insurance and may lead to more expedited testing.
  • Participants with a germline deleterious BRCA mutation or BRCA1 or BRCA2 classified as "variant, suspected deleterious" by Myriad Genetics will not be eligible for the trial. Participants without a mutation or with only a BRCA1 or BRCA2 VUS (variant of uncertain significance) as classified by Myriad Genetics will be eligible for this study.
  • Although strongly recommended, genetic testing will not be mandatory. If a patient refuses to perform genetic testing but is otherwise eligible for the study, enrollment will be allowed.
  • Breast imaging should include imaging of the ipsilateral axilla. For subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will be performed to confirm the presence of metastatic disease in the lymph nodes. For patients with a clinically negative axilla, baseline assessment of the axilla will be performed at the discretion of the treating investigator. For patients with pathologically positive axillary lymph nodes prior to preoperative therapy, a level I and II lymph node dissection at the time of definitive surgery is recommended.
  • Participants with axillary adenopathy only are not eligible for this study.
  • Patients with a prior history of contra-lateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer within the last 5 years.
  • Women ≥ 18 years of age.
  • ECOG performance status ≤1 (see Appendix A).

Laboratory Evaluation

  • Absolute neutrophil count (ANC) ≥ 1,500 / mm3
  • Platelet count ≥ 100,000/ mm3
  • Bilirubin ≤ 1.5x upper limit of normal (ULN), for patients with Gilbert syndrome, direct bilirubin will be measured instead of total bilirubin ALT, AST, ALK Phos ≤2.5 x ULN
  • Creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 cc/min
  • Hemoglobin ≥ 9 mg/dl
  • Use of an effective means of contraception is required in subjects of childbearing potential since study agents are known to be teratogenic. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Ability to understand and the willingness to sign a written informed consent document
  • Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy and did not receive prior chemotherapy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
  • Patient must be willing to undergo mandatory research biopsy and blood draw. Prior to biopsy procedures patients must be able to be off medications that could increase the risk of bleeding

Exclusion Criteria:

  • Any prior chemotherapy at any time.
  • Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy.
  • Ipsilateral breast recurrence, unless prior treatment consisted of excision alone for DCIS or breast conserving treatment and hormonal therapy for DCIS or invasive breast cancer.
  • Ongoing use of any other investigational or study agents.
  • Peripheral neuropathy of any etiology > grade 1 (NCI CTCAE Version 4.0- Appendix B)
  • Significant hearing loss that would prevent cisplatin administration.
  • Renal dysfunction for which exposure to cisplatin would be unsafe or require cisplatin dose modification (i.e., Cre > 1.5 mg/dl or GFR < 60 cc/min).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01982448

Contacts
Contact: Erica Mayer, MD 617-632-2335 EMAYER@PARTNERS.ORG

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Nadine Tung, MD    617-667-1962    ntung@bidmc.harvard.edu   
Principal Investigator: Nadine Tung, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Erica Mayer, MD, MPH    617-632-2335    emayer@partners.org   
Principal Investigator: Erica Mayer, MD, MPH         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Myriad Genetics
Investigators
Principal Investigator: Erica Mayer, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Erica Mayer, MD, MPH, Principal Invesitigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01982448     History of Changes
Other Study ID Numbers: 13-383
Study First Received: October 28, 2013
Last Updated: February 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
TRIPLE NEGATIVE BREAST CANCER WITHOUT GERMLINE BRCA MUTATIONS
CISPLATIN
PACLITAXEL

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cisplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014