Randomized Controlled Trial of Genomically Directed Therapy in Patients With Triple Negative Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Hoosier Cancer Research Network
Sponsor:
Collaborators:
Hoosier Cancer Research Network
Vera Bradley Foundation for Breast Cancer
Walther Cancer Institute
Strategic Research Initiative Grant through IUSCC
Information provided by (Responsible Party):
Bryan Schneider, MD, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT02101385
First received: March 21, 2014
Last updated: March 22, 2016
Last verified: March 2016
  Purpose
This study will test the theory that therapy designed for each individual's tumor will improve outcomes over standard of care in a population that needs a better standard.

Condition Intervention Phase
Malignant Neoplasm of Breast
Breast Cancer
Drug: Genomically Directed Monotherapy
Other: Observation/Standard Therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized Controlled Trial of Genomically Directed Therapy After Preoperative Chemotherapy in Patients With Triple Negative Breast Cancer: Hoosier Oncology Group BRE12-158

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Two-Year Disease-Free Survival (DFS) Rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    To compare 2-year disease-free survival (DFS) in participants with confirmed triple negative breast cancer (TNBC) treated with a genomically directed therapy or standard of care following preoperative chemotherapy


Secondary Outcome Measures:
  • One-Year Disease-Free Survival (DFS) Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To compare overall DFS and 1-year DFS in participants with confirmed triple negative breast cancer (TNBC) treated with a genomically directed therapy or standard of care following preoperative chemotherapy

  • Five-Year Overall Survival (OS) Rate [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    To determine 5-year overall survival (OS) in participants with confirmed triple negative breast cancer (TNBC) treated with a genomically directed therapy or standard of care following preoperative chemotherapy

  • Number of Patients with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    To determine the toxicities associated with genomically directed therapies in this population

  • Clinical and Demographic Characteristics of Tumor Specimens [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    To determine recurrence rates correlated with genomic characteristics in tumor specimens.

  • Drug Specific Toxicity Rate [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Toxicity rates will be reported for each individual drug used in the study.


Estimated Enrollment: 136
Study Start Date: March 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (Genomically Directed Monotherapy)
Participants randomized to Experimental Arm A will receive an FDA approved drug at standard dose for four cycles (12-16 weeks total duration, depending on cycle length). Clinical and laboratory monitoring and dose-reductions will follow the FDA package insert guidelines.
Drug: Genomically Directed Monotherapy
Participants randomized to Experimental Arm A will receive an FDA approved drug at standard dose for four cycles (12-16 weeks total duration, depending on cycle length). The CGTB will assign therapy to each participant individually based on biomarkers/pathways identified by DNA sequencing:
Control Arm B (Observation/Standard Therapy)
Currently no standard therapy has proven efficacy in this patient population and thus observation alone would be considered standard of care. Additional therapy is permitted, however, if deemed appropriate by the treating physician.
Other: Observation/Standard Therapy
Currently no standard therapy has proven efficacy in this patient population and thus observation alone would be considered standard of care. Additional therapy is permitted, however, if deemed appropriate by the treating physician.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER2-) invasive breast cancer, clinical stage I-III at diagnosis (AJCC 6th edition) based on initial evaluation by physical examination and/or breast imaging prior to study registration. NOTE: ER, PR and HER2 status will be confirmed by central pathology review prior to randomization. ER and PR will be considered negative if ≤ 1% of cells stain weakly positive. HER2 will be considered negative if scored 0 or 1+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of < 2.0 or < 6 copies per cell.
  • Must have completed preoperative (neoadjuvant) chemotherapy. NOTE: Acceptable preoperative regimens include an anthracycline or a taxane, or both. Participants who received preoperative therapy as part of a clinical trial may enroll. Participants may not have received adjuvant chemotherapy after surgery prior to randomization. Bisphosphonate use is allowed.
  • Must have completed definitive resection of primary tumor. The most recent surgery for breast cancer must have been completed at least 14 days prior (but no more than 84 days prior) to study registration. NOTE: Negative margins for both invasive and ductal carcinoma in situ (DCIS) are desirable, however participants with positive margins may enroll if the treatment team believes no further surgery is possible and patient has received radiotherapy. Participants with margins positive for lobular carcinoma in situ (LCIS) are eligible. Either mastectomy or breast conserving surgery (including lumpectomy or partial mastectomy) is acceptable.
  • Must have significant residual invasive disease at the time of definitive surgery following preoperative chemotherapy. Significant residual disease is defined as at least one of the following:

    • Residual Cancer Burden (RBC) classification II or III6
    • Residual invasive disease in the breast measuring at least 2 cm. The presence of DCIS without invasion does not qualify as residual disease in the breast.
    • Residual invasive disease in the breast measuring at least 1cm with any lymph node involvement (does not include metastases in lymph node which are only detected by immunohistochemistry).
    • Any lymph node involvement that results in 20% cellularity or greater regardless of primary tumor site involvement (includes no residual disease in the breast).
  • Must have an FFPE tumor block with tumor cellularity of 20% or greater. NOTE: Prior to randomization, the tumor cellularity will be confirmed by central pathology review and percent values will be double checked at Paradigm (a Next Generation Sequencing Company).
  • BREAST RADIOTHERAPY:

    • Whole breast radiotherapy is required for participants who underwent breast-conserving therapy, including lumpectomy or partial mastectomy. Participants must have completed radiotherapy at least 14 days prior (but no more than 84 days prior) to study registration.
    • Post-mastectomy radiotherapy is required for all participants with a primary tumor ≥ 5 cm or involvement of ≥ 4 lymph nodes. For participants with primary tumors < 5 cm or with < 4 involved lymph nodes, provision of post-mastectomy radiotherapy is at the discretion of the treating physician. Study registration must occur within 84 days of completion of radiation.
    • For radiation required prior to surgery, the participant must register within 84 days of surgery. Also, participants in this situation would not be required to have additional post-mastectomy radiation therapy.
    • For those participants who do not require radiation, registration must be within 84 days of surgery.
  • Age ≥ 18 years at the time of consent.
  • Written informed consent and HIPAA authorization for release of personal health information. HIPAA authorization may be included in the informed consent or may be obtained separately. NOTE: Central pathology review may be conducted any time after definitive surgery. Consenting participants may be pre-registered to the study and proceed with central pathology review before full eligibility has been confirmed. However ALL of the eligibility criteria must be met and formal study registration completed prior to submission of the sample for sequencing.
  • Must consent to allow submission of adequate archived tumor tissue sample from definitive surgery for genomic assessment of tumor.
  • Must consent to collection of whole blood samples for genomic analysis
  • Women and men of childbearing potential must be willing to use an effective method of contraception (e.g. hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after protocol therapy discontinuation.
  • Women of childbearing potential must have a negative pregnancy test within 30 days prior to study registration. Women should be counseled regarding acceptable birth control methods to utilize from the time of screening to start of treatment. If prior to treatment after discussion with the subject it is felt by the treating physician there is a possibility the subject is pregnant a pregnancy test should be repeated.

Women of childbearing potential must have a negative pregnancy test within 30 days prior to study registration.

  • Women must not be breastfeeding.

Exclusion Criteria:

  • No stage IV (metastatic) disease, however no specific staging studies are required in the absence of symptoms or physical exam findings that would suggest distant disease.
  • No treatment with any investigational agent within 30 days prior to study registration.
  • No history of chronic hepatitis B or or untreated hepatitis C.
  • No clinically significant infections as judged by the treating physician.
  • No active second malignancy (except non-melanomatous skin cancer or incidental prostate cancer found on cystectomy): Active second malignancy is defined as a current need for cancer therapy or a high possibility (> 30%) of recurrence during the study. Previous contralateral breast cancer is allowable unless it meets "active" criteria as stated above.
  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: NCT02101385

Contacts
Contact: Bryan Schneider, M.D. 317.944.0920 bpschnei@iu.edu
Contact: Lauren Wiehl 317.634.5842 ext 38 lhyer@hoosiercancer.org

  Show 25 Study Locations
Sponsors and Collaborators
Bryan Schneider, MD
Hoosier Cancer Research Network
Vera Bradley Foundation for Breast Cancer
Walther Cancer Institute
Strategic Research Initiative Grant through IUSCC
Investigators
Study Chair: Bryan Schneider, M.D. Hoosier Cancer Research Network
  More Information

Additional Information:
Responsible Party: Bryan Schneider, MD, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT02101385     History of Changes
Other Study ID Numbers: BRE12-158 
Study First Received: March 21, 2014
Last Updated: March 22, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Hoosier Cancer Research Network:
Genomically-Directed Therapy
DNA Sequencing
RNA Sequencing

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on July 26, 2016