Malignant Neoplasm of BreastPhase 2NCT02101385
Randomized Controlled Trial of Genomically Directed Therapy in Patients With Triple Negative Breast Cancer
A Phase 2 study testing Genomically Directed Monotherapy and Observation/Standard Therapy in people with Malignant Neoplasm of Breast and Breast Cancer, run by Bryan Schneider, MD at 29 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Neoplasm of Breast, Breast Cancer
- What is being tested?
- Genomically Directed Monotherapy and Observation/Standard Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 193 participants
- Where
- 29 sitesUnited States
- Study dates
- 3 Apr 2014to 9 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -Written informed consent and HIPAA authorization for release of personal health information.
- NOTE: 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.
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status 0 or 1 within 14 days prior to study registration.
- 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.
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- 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.
- NOTE: Women are considered not of childbearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or they are postmenopausal for at least 12 consecutive months.
- Women must not be breastfeeding.
- 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 III^6
- 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.
- Participants with a primary tumor > 5 cm or involvement of ≥4 lymph nodes who require a mastectomy must also have radiotherapy pre- or post-operatively at the discretion of the treating physician. 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. Registration must occur within 84 days of the completion of the last local therapy.
- 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.
- 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 untreated hepatitis C.
- Adequate laboratory values must be obtained within 14 days prior to study registration.
- Hemoglobin (Hgb) >/= 9.0 g/dL
- Platelets >/= 100 K/mm^3
- Absolute neutrophile count (ANC) >/= 1.5 K/mm^3
- Calculated creatinine clearance of >/= 50 cc/min using the Cockcroft-Gault formula:
- Males: (140-Age in years) x Actual body weight in kg / 72 x Serum creatinine (mg/dL)
- Females: Estimated creatinine clearaNCE FOR MALES X 0.85
- Bilirubin </= 1.5 x ULN (except in participants with documented Gilbert's disease, who must have a total bilirubin </= 3.0 mg/dL)
- Aspartate aminotransferase (AST, SGOT) </= 2.5 x ULN
- Alanine aminotransferase (ALT, SGPT) </= 2.5 x ULN
- Left ventricular ejection fraction within normal limits obtained within 30 days prior to study registration.
- NOTE: Participants with an unstable angina or myocardial infarction within 12 months of study registration are excluded.
- No clinically significant infections as judged by the treating physician.
- 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
- No clinically significant arrhythmia or baseline ECG abnormalities in the opinion of the treating physician.
Who cannot join
- 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.
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
United States29 sites
Community Hospital of Anderson and Madison County, Inc
Anderson, Indiana, 46011
Emory University: Winship Cancer Institute
Atlanta, Georgia, 30322
University of Alabama Hematology Oncology Clinic at Medical West
Birmingham, Alabama, 35294
Tufts Medical Center
Boston, Massachusetts, 02111
Erlanger Health System
Chattanooga, Tennessee, 37403
University of Chicago Medicine
Chicago, Illinois, 60637
University of Cincinnati Cancer Institute
Cincinnati, Ohio, 45267
Fort Wayne Oncology & Hematology, Inc.
Fort Wayne, Indiana, 46845
University of Florida: Shands Cancer Center
Gainesville, Florida, 32610
IU Health Goshen Hospital
Goshen, Indiana, 46527
Meritus Center for Clinical Research
Hagerstown, Maryland, 21742
Pinnacle Health Cancer Center
Harrisburg, Pennsylvania, 17109
Memorial Cancer Institute
Hollywood, Florida, 33021
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Community Regional Cancer Center
Indianapolis, Indiana, 46256
St. Vincent Hospital
Indianapolis, Indiana, 46260
IU Health Arnett Cancer Center
Lafayette, Indiana, 47904
Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, 79410
University of Miami, Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Froedtert/Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Community Healthcare System: Monroe Medical Associates
Munster, Indiana, 46321
Virginia Oncology Associates
Norfolk, Virginia, 23502
Mercy Clinic Oncology & Hematology: McAuley
Oklahoma City, Oklahoma, 73120
Nebraska Cancer Specialists
Omaha, Nebraska, 68114
Memorial Breast Cancer Center: Memorial West
Pembroke Pines, Florida, 33028
Northern Indiana Cancer Research Consortium
South Bend, Indiana, 46628
Washington University: Siteman Cancer Center
St Louis, Missouri, 63110
Georgetown University: Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
Aurora Health Care
Wauwatosa, Wisconsin, 53226
About this study
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
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.
Read the detailed description
OUTLINE: This is a multi-center trial.
SEQUENCING:
DNA from archived tumor samples collected at the time of surgery (residual disease post neoadjuvant chemotherapy) will be extracted and sequenced. The resulting sequencing data will be interrogated for known genomic drivers of sensitivity or resistance to existing FDA approved agents.
CANCER GENOMICS TUMOR BOARD (CGTB):
Realizing that optimal treatment recommendations cannot be made based on sequencing data alone, the CGTB will be responsible for the final treatment recommendation. The CGTB will consider the genomic data along with the patient's prior treatment history, ongoing toxicities, and comorbidities. Preference will be given to the treatment identified by the sequencing data unless a significant clinical or safety contraindication exists for that therapy. All participants and investigators will be blinded to sequencing results and CGTB deliberations until the time of relapse.
PARTICIPANTS WITH A CGTB TREATMENT RECOMMENDATION:
Participants with a CGTB recommendation will be randomized to Experimental Arm A (genomically directed monotherapy) or Control Arm B (standard therapy).
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.
TOP GENOMIC ACTIONABLE BIOMARKERS/PATHWAYS AND DRUG RECOMMENDATIONS:
- PIK3CA, PTEN: Everolimus
- TOP2A: Doxorubicin
- PARP1, BRCA1: Cisplatin and Olaparib
- VEGFA: Bevacizumab
- TYMP: Capecitabine
- SSTR2: Octreotide
- MGMT: Temozolomide
- MYC: Paclitaxel
- EGFR: Cetuximab
- COX2: Celecoxib
- hENT: Gemcitabine
- MET: Crizotinib
CONTROL ARM B (STANDARD THERAPY); Recently, a randomized phase III trial of over 900 HER2-negative patients demonstrated an improvement in disease-free survival (DFS) and overall survival (OS) for the addition of 8 cycles of capecitabine in the post-neoadjuvant setting. The hazard ratios were also significant in the triple negative subgroup. Thus, capecitabine can be considered a standard option in this setting. As this represents only a single trial (with prior data not demonstrating benefit for the addition of capecitabine in the neoadjuvant nor adjuvant settings in unselected patients), observation can be considered an option as directed by the treating physician. While not recommended, other therapies can be used as deemed appropriate by the treating physician.
In the event of disease progression on the control arm, patient sequencing results will be forwarded to the treating physician.
PARTICIPANTS WITH NO CGTB RECOMMENDATION:
Participants may have no CGTB recommendation either because 1) sequencing did not identify a matched drug or 2) the matched drug was contraindicated. These participants will be assigned to Control Arm B and treated as described above for Control Arm B. As the outcome of participants without an 'actionable' genomically directed therapy may differ, the primary analysis will include only participants randomized to Control Arm B.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days prior to study registration
Life Expectancy: Not Specified
Adequate laboratory values must be obtained within 14 days prior to study registration:
Hematopoietic:
- Hemoglobin (Hgb) ≥ 9.0 g/dL
- Platelets ≥ 100 K/mm3
- Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
Hepatic:
- Bilirubin ≤ 1.5 x ULN (except in participants with documented Gilbert's disease, who must have a total bilirubin ≤ 3.0 mg/dL)
- Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN
- Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN
Renal:
- Calculated creatinine clearance of ≥ 50 cc/min using the Cockcroft-Gault formula
Cardiac:
- Left ventricular ejection fraction within normal limits obtained within 30 days prior to study registration. NOTE: Participants with an unstable angina or myocardial infarction within 12 months of study registration are excluded.
- No clinically significant arrhythmia or baseline ECG abnormalities in the opinion of the treating physician
- Conditions
- Malignant Neoplasm of Breast, Breast Cancer
- Being tested
- Genomically Directed Monotherapy, Observation/Standard Therapy
- Keywords
- Genomically-Directed Therapy, DNA Sequencing, RNA Sequencing
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genomically Directed MonotherapyDrug
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:
Observation/Standard TherapyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Genomically Directed Monotherapy) | Experimental | 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. Receives: Drug: Genomically Directed Monotherapy |
| Control Arm B (Observation/Standard Therapy) | Other | 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. Receives: Other: Observation/Standard Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Two-Year Disease-Free Survival (DFS)
Two-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. The survival probabilities for arm A and arm B were estimated as 2 year disease free survival.
DFS is defined as the duration of time from randomization to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
Measured: From C1D1 until death or up to a maximum of 24 months.
Secondary outcomes (4)
Comparison Between Overall Disease-Free Survival
Overall DFS in participants of arm A and B were compared with confirmed triple negative breast cancer (TNBC) treated with a genomically directed therapy or standard of care following preoperative chemotherapy.
DFS is defined as the duration of time from randomization to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
Measured: From C1D1 until death or up to a maximum of 58 months
Comparison Between One Year Disease Free Survival
One year DFS in participants of arm A and B were compared with confirmed triple negative breast cancer (TNBC) treated with a genomically directed therapy or standard of care following preoperative chemotherapy. The survival probabilities for arm A and arm B were estimated as 1 year disease free survival.
Disease Free Survival is defined as the duration of time from randomization to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
Measured: From C1D1 until death or up to a maximum of 12 months
Five-Year Overall Survival (OS) Rate
5-year overall survival (OS) in participants is determind with confirmed triple negative breast cancer (TNBC) treated with a genomically directed therapy or standard of care following preoperative chemotherapy. Here 5 - year survival probability to compare arms A and B has been reported.
Overall Survival is defined as the time from start of treatment to death from any cause. Subjects who are alive are censored at their last visit dates.
Measured: From C1D1 until death or up to a maximum of 60 months
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
The safety and tolerability of the experimental arm A(genomically directed monotherapy) and control arm B(standard therapy) has been assessed using CTCAE v4.0. Number of subjects who had any adverse events or events greater than grade 3 were reported in this outcome measure.
Measured: From C1D1 until death or up to a maximum of 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2014 (estimated)
- Study start3 Apr 2014
- Primary completion21 Feb 2021
- Study completion9 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Malignant Neoplasm of BreastStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 193 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bryan Schneider, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Hoosier Cancer Research Network, Vera Bradley Foundation for Breast Cancer, Walther Cancer Institute, Indiana University
- Responsible party
- Sponsor-investigator, Bryan Schneider, MD, Hoosier Cancer Research Network
- Investigators
- Bryan Schneider, M.D., Study chair, Hoosier Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02101385
- Sponsor's protocol ID
- BRE12-158
- Status last verified
- Aug 2023
- First submitted
- 21 Mar 2014
- Last updated
- 28 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Xu J, Gao H, Guan X, Meng J, Ding S, Long Q, Yi W. Circulating tumor DNA: from discovery to clinical application in breast cancer. Front Immunol. 2024 Apr 30;15:1355887. doi: 10.3389/fimmu.2024.1355887. eCollection 2024.
PubMed 38745646Schneider BP, Jiang G, Ballinger TJ, Shen F, Chitambar C, Nanda R, Falkson C, Lynce FC, Gallagher C, Isaacs C, Blaya M, Paplomata E, Walling R, Daily K, Mahtani R, Thompson MA, Graham R, Cooper ME, Pavlick DC, Albacker LA, Gregg J, Solzak JP, Chen YH, Bales CL, Cantor E, Hancock BA, Kassem N, Helft P, O'Neil B, Storniolo AMV, Badve S, Miller KD, Radovich M. BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer. J Clin Oncol. 2022 Feb 1;40(4):345-355. doi: 10.1200/JCO.21.01657. Epub 2021 Dec 15.
PubMed 34910554Radovich M, Jiang G, Hancock BA, Chitambar C, Nanda R, Falkson C, Lynce FC, Gallagher C, Isaacs C, Blaya M, Paplomata E, Walling R, Daily K, Mahtani R, Thompson MA, Graham R, Cooper ME, Pavlick DC, Albacker LA, Gregg J, Solzak JP, Chen YH, Bales CL, Cantor E, Shen F, Storniolo AMV, Badve S, Ballinger TJ, Chang CL, Zhong Y, Savran C, Miller KD, Schneider BP. Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1410-1415. doi: 10.1001/jamaoncol.2020.2295.
PubMed 32644110
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02101385
- Acronym / sponsor ID
- BRE12-158
- Conditions
- Malignant Neoplasm of Breast, Breast Cancer
- Keywords
- Genomically-Directed Therapy, DNA Sequencing, RNA Sequencing
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 193 participants (actual)
- Lead sponsor
- Bryan Schneider, MDUniversity, hospital or other
- Collaborators
- Hoosier Cancer Research Network, Vera Bradley Foundation for Breast Cancer, Walther Cancer Institute, Indiana University
- Study start
- 3 Apr 2014 (actual)
- Primary completion
- 21 Feb 2021 (actual)
- Study completion
- 9 Sep 2022 (actual)
- First posted
- 2 Apr 2014 (estimated)
- Results
- Posted 28 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OUTLINE: This is a multi-center trial.
SEQUENCING:
DNA from archived tumor samples collected at the time of surgery (residual disease post neoadjuvant chemotherapy) will be extracted and sequenced. The resulting sequencing data will be interrogated for known genomic drivers of sensitivity or resistance to existing FDA approved agents.
CANCER GENOMICS TUMOR BOARD (CGTB):
Realizing that optimal treatment recommendations cannot be made based on sequencing data alone, the CGTB will be responsible for the final treatment recommendation. The CGTB will consider the genomic data along with the patient's prior treatment history, ongoing toxicities, and comorbidities. Preference will be given to the treatment identified by the sequencing data unless a significant clinical or safety contraindication exists for that therapy. All participants and investigators will be blinded to sequencing results and CGTB deliberations until the time of relapse.
PARTICIPANTS WITH A CGTB TREATMENT RECOMMENDATION:
Participants with a CGTB recommendation will be randomized to Experimental Arm A (genomically directed monotherapy) or Control Arm B (standard therapy).
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.
TOP GENOMIC ACTIONABLE BIOMARKERS/PATHWAYS AND DRUG RECOMMENDATIONS:
- PIK3CA, PTEN: Everolimus
- TOP2A: Doxorubicin
- PARP1, BRCA1: Cisplatin and Olaparib
- VEGFA: Bevacizumab
- TYMP: Capecitabine
- SSTR2: Octreotide
- MGMT: Temozolomide
- MYC: Paclitaxel
- EGFR: Cetuximab
- COX2: Celecoxib
- hENT: Gemcitabine
- MET: Crizotinib
CONTROL ARM B (STANDARD THERAPY); Recently, a randomized phase III trial of over 900 HER2-negative patients demonstrated an improvement in disease-free survival (DFS) and overall survival (OS) for the addition of 8 cycles of capecitabine in the post-neoadjuvant setting. The hazard ratios were also significant in the triple negative subgroup. Thus, capecitabine can be considered a standard option in this setting. As this represents only a single trial (with prior data not demonstrating benefit for the addition of capecitabine in the neoadjuvant nor adjuvant settings in unselected patients), observation can be considered an option as directed by the treating physician. While not recommended, other therapies can be used as deemed appropriate by the treating physician.
In the event of disease progression on the control arm, patient sequencing results will be forwarded to the treating physician.
PARTICIPANTS WITH NO CGTB RECOMMENDATION:
Participants may have no CGTB recommendation either because 1) sequencing did not identify a matched drug or 2) the matched drug was contraindicated. These participants will be assigned to Control Arm B and treated as described above for Control Arm B. As the outcome of participants without an 'actionable' genomically directed therapy may differ, the primary analysis will include only participants randomized to Control Arm B.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days prior to study registration
Life Expectancy: Not Specified
Adequate laboratory values must be obtained within 14 days prior to study registration:
Hematopoietic:
- Hemoglobin (Hgb) ≥ 9.0 g/dL
- Platelets ≥ 100 K/mm3
- Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
Hepatic:
- Bilirubin ≤ 1.5 x ULN (except in participants with documented Gilbert's disease, who must have a total bilirubin ≤ 3.0 mg/dL)
- Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN
- Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN
Renal:
- Calculated creatinine clearance of ≥ 50 cc/min using the Cockcroft-Gault formula
Cardiac:
- Left ventricular ejection fraction within normal limits obtained within 30 days prior to study registration. NOTE: Participants with an unstable angina or myocardial infarction within 12 months of study registration are excluded.
- No clinically significant arrhythmia or baseline ECG abnormalities in the opinion of the treating physician
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (Genomically Directed Monotherapy) | Experimental | Drug: Genomically Directed MonotherapyParticipants 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. |
| Control Arm B (Observation/Standard Therapy) | Other | Other: Observation/Standard TherapyCurrently 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (42 listed)
- -Written informed consent and HIPAA authorization for release of personal health information.
- NOTE: 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.
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status 0 or 1 within 14 days prior to study registration.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genomically Directed MonotherapyParticipants 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: | Drug | Arm A (Genomically Directed Monotherapy) |
| Observation/Standard TherapyCurrently 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 | Control Arm B (Observation/Standard Therapy) |
Primary outcome
Percentage of Participants With Two-Year Disease-Free Survival (DFS)
Time frame: From C1D1 until death or up to a maximum of 24 months.
Two-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. The survival probabilities for arm A and arm B were estimated as 2 year disease free survival. DFS is defined as the duration of time from randomization to time of a DFS event, defined as local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive or non-invasive), or death from any cause.
4 secondary outcomes
Comparison Between Overall Disease-Free Survival
Time frame: From C1D1 until death or up to a maximum of 58 months
Comparison Between One Year Disease Free Survival
Time frame: From C1D1 until death or up to a maximum of 12 months
Five-Year Overall Survival (OS) Rate
Time frame: From C1D1 until death or up to a maximum of 60 months
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Time frame: From C1D1 until death or up to a maximum of 60 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38745646Xu J, Gao H, Guan X, Meng J, Ding S, Long Q, Yi W. Circulating tumor DNA: from discovery to clinical application in breast cancer. Front Immunol. 2024 Apr 30;15:1355887. doi: 10.3389/fimmu.2024.1355887. eCollection 2024.
- Derived from this study: PubMed 34910554Schneider BP, Jiang G, Ballinger TJ, Shen F, Chitambar C, Nanda R, Falkson C, Lynce FC, Gallagher C, Isaacs C, Blaya M, Paplomata E, Walling R, Daily K, Mahtani R, Thompson MA, Graham R, Cooper ME, Pavlick DC, Albacker LA, Gregg J, Solzak JP, Chen YH, Bales CL, Cantor E, Hancock BA, Kassem N, Helft P, O'Neil B, Storniolo AMV, Badve S, Miller KD, Radovich M. BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer. J Clin Oncol. 2022 Feb 1;40(4):345-355. doi: 10.1200/JCO.21.01657. Epub 2021 Dec 15.
- Derived from this study: PubMed 32644110Radovich M, Jiang G, Hancock BA, Chitambar C, Nanda R, Falkson C, Lynce FC, Gallagher C, Isaacs C, Blaya M, Paplomata E, Walling R, Daily K, Mahtani R, Thompson MA, Graham R, Cooper ME, Pavlick DC, Albacker LA, Gregg J, Solzak JP, Chen YH, Bales CL, Cantor E, Shen F, Storniolo AMV, Badve S, Ballinger TJ, Chang CL, Zhong Y, Savran C, Miller KD, Schneider BP. Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1410-1415. doi: 10.1001/jamaoncol.2020.2295.
- Hoosier Cancer Research Network WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bryan Schneider, M.D. study chair
Hoosier Cancer Research Network
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Genomically Directed Monotherapy and Observation/Standard Therapy in people with Malignant Neoplasm of Breast and Breast Cancer, run by Bryan Schneider, MD at 29 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 42 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Two-Year Disease-Free Survival (DFS) (time frame: From C1D1 until death or up to a maximum of 24 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02101385, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.