Cisplatin vs Paclitaxel for Triple Negative Breast Cancer

NCT ID: NCT01982448

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 147 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2020-08-31

Brief Summary

This is a phase II study randomizing patients with stage I with T1 > 1.5 cm, stage II or III triple negative breast cancer (TNBC) to preoperative cisplatin versus paclitaxel. The study is designed to evaluate the ability of the Homologous Recombination Deficiency (HRD) assay to predict pathologic response to preoperative chemotherapy.

Detailed Description

Cisplatin and paclitaxel are active in triple-negative breast cancer (TNBC). Despite different mechanisms of action, effective predictive biomarkers to preferentially inform drug selection have not been identified. The homologous recombination deficiency (HRD) assay (Myriad Genetics, Inc.) detects impaired double-strand DNA break repair and may identify patients with BRCA1/2-proficient tumors that are sensitive to DNA-targeting therapy. The primary objective of TBCRC 030 was to detect an association of HRD with pathologic response (residual cancer burden (RCB)-0/1) to singleagent cisplatin or paclitaxel. This prospective phase II study enrolled patients with germline BRCA1/2 wild-type/unknown stage I-III TNBC in a 12-week randomized study of preoperative cisplatin or paclitaxel. The HRD assay was carried out on baseline tissue; positive HRD was defined as a score >=33. Crossover to an alternative chemotherapy was offered if there was inadequate response.

Conditions

Triple Negative Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Cisplatin

Cisplatin given by IV infusion at a dose of 75 mg/m2 every 3 weeks (1 cycle) for 4 cycles as preoperative chemotherapy. Participants with inadequate clinical response after 12 weeks (as judged either clinically or radiologically by a provider) were able to crossover to an alternative provider-selected preoperative chemotherapy regimen. Definitive breast surgery following no later than 42 days after administration of last chemotherapy.

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

Arm B: Paclitaxel

Paclitaxel given by IV infusion at a dose of 80 mg/m2 weekly for 12 weeks (4 cycles) as neoadjuvant chemotherapy. Participants with inadequate clinical response after 12 weeks (as judged either clinically or radiologically by a provider) were able to 'crossover' to an alternative provider-selected preoperative chemotherapy regimen. Definitive breast surgery following no later than 42 days after administration of last chemotherapy.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Interventions

Cisplatin

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Other Intervention Names

Platinol ®-AQ; Taxol

Eligibility Criteria

Inclusion Criteria

Inclusion Criteria: 1. Participants must meet the following criteria on screening examination to be eligible to participate in the study 2. Pathologic documentation of invasive breast cancer by biopsy (FNA alone is not adequate). 3. AJCC clinical stage I with T1 > 1.5 cm, stage II or III invasive breast cancer. 4. 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. 5. 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. 6. ER and PgR status by IHC must be known. Tumor must be ER and PR negative (≤5% staining) by local review. 7. Known BRCA1/2 (BReast CAncer) status is not required for study entry. However patients known to have a germline deleterious BRCA1/2 mutation should be encouraged to consider a preoperative trial specifically designed for BRCA1/2 carriers, if available. 8. 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. 9. 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. 10. Women ≥ 18 years of age. 11. ECOG performance status ≤1 (see Appendix A). 12. Laboratory Evaluation 1) Absolute neutrophil count (ANC) ≥ 1,500 / mm3 2) Platelet count ≥ 100,000/ mm3 3) Bilirubin ≤ 1.5x upper limit of normal (ULN), for patients with Gilbert syndrome, direct bilirubin will be measured instead of total bilirubin 4) ALT, AST ≤3.0 x ULN ALK Phos <2.5 x ULN 5) Creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 cc/min 6) Hemoglobin ≥ 9 mg/dl 7) 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. 8) Ability to understand and the willingness to sign a written informed consent document 9) 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. 10) Patient must be willing to undergo mandatory research biopsy and blood draw.

Exclusion Criteria

Prior to biopsy procedures patients must be able to be off medications that could increase the risk of bleeding Exclusion Criteria: 1. Participants with axillary adenopathy only are not eligible for this study. 2. Prior chemotherapy: Prior non-taxane or platinum containing chemotherapy will be allowed if the prior exposure was at least 5 years ago and the exposure is thought not to potentially interact with the primary outcome of the trial or put the patient at undue risk, and should be reviewed with study PI on a case by case basis. 3. Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy. 4. 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. 5. Ongoing use of any other investigational or study agents. 6. Peripheral neuropathy of any etiology > grade 1 (NCI CTCAE Version 4.0- Appendix B) 7. Significant hearing loss that would prevent cisplatin administration. 8. 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Myriad Genetics, Inc.

INDUSTRY

Sponsor Role: collaborator

Translational Breast Cancer Research Consortium

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Erica Mayer, MD, MPH

Principal Invesitigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Erica Mayer, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

University of Alabama

Birmingham, Alabama, United States

Indiana University- Simon Cancer Center

Indianapolis, Indiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

South Shore Hospital

Weymouth, Massachusetts, United States

Memorial Sloan Kettering Cancer Center-Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Cancer Center-Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Cancer Center-Commack

Commack, New York, United States

Memorial Sloan Kettering Cancer Center-West Harrison

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center-Rockville Centre

Rockville Centre, New York, United States

Memorial Sloan Kettering Cancer Center-Sleepy Hollow

Sleepy Hollow, New York, United States

University of North Carolina- Lineberger Cancer Center

Chapel Hill, North Carolina, United States

Duke University

Durham, North Carolina, United States

Universtiy of Pittsburgh- Magee-Womens Hospital

Pittsburgh, Pennsylvania, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

Seattle Cancer Alliance at EvergreenHealth

Kirkland, Washington, United States

University of Washignton

Seattle, Washington, United States

Countries

United States

References

Mayer EL, Abramson V, Jankowitz R, Falkson C, Marcom PK, Traina T, Carey L, Rimawi M, Specht J, Miller K, Stearns V, Tung N, Perou C, Richardson AL, Componeschi K, Trippa L, Tan-Wasielewski Z, Timms K, Krop I, Wolff AC, Winer EP. TBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker. Ann Oncol. 2020 Nov;31(11):1518-1525. doi: 10.1016/j.annonc.2020.08.2064. Epub 2020 Aug 13.

Reference Type: RESULT

PMID: 32798689 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/32798689/

Related Info

Other Identifiers

TBCRC030

Identifier Type: OTHER

Identifier Source: secondary_id

13-383

Identifier Type: -

Identifier Source: org_study_id