Neoadjuvant Platinum-based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer

NCT01167192 | Terminated Phase 2 Results

• 1 other identifier: 201310089
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether platinum-based chemotherapy (either cisplatin or carboplatin), when given with radiation therapy prior to surgery, is effective in improving response to treatment in triple negative breast cancer patients. This treatment is being studied in this type of breast cancer because it does not respond well to commonly used treatments such as tamoxifen or herceptin.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (2)

• Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR)

  * Complete response (CR) = disappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR) = at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD

  Prior to surgery (approximately 12-16 weeks from registration)

• Relationship Between Tumor Response and Deficiencies in DNA Repair Mechanisms

  Prior to surgery (approximately 12-16 weeks from registration)

Secondary Outcomes (10)

• Time to Disease Progression

  Up to 5 years from registration

• Number of Participants With Surgical Complications

  30 days post surgery (approximately 16-20 weeks from registration)

• Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow

  Up to 15 months from registration

• Overall Survival Rate

  Median follow-up was 59.9 months

• Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events

  30 days post surgery (approximately 16-20 weeks after start of registration)

Study Arms (1)

Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation

EXPERIMENTAL

Cisplatin 75 mg/m\^2 IV every 21 days for 4 cycles or Carboplatin AUC 6 IV every 21 days for 4 cycles. Radiation beginning cycle 2 day 1 daily for 5-6 weeks 45-50 Gy. Recommended mastectomy Recommended adjuvant chemotherapy -doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m2 for 14 days for 4 cycles)

Drug: Cisplatin; Drug: Carboplatin; Radiation: Radiation therapy; Procedure: Mastectomy (recommended but not mandatory)

Interventions

Cisplatin DRUG

Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation

Carboplatin DRUG

Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation

Radiation therapy RADIATION

Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation

Mastectomy (recommended but not mandatory) PROCEDURE

Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be \> or = 18 years of age
• Patient must be female
• Patient must have primary invasive ductal breast adenocarcinoma that either:
• is newly diagnosed, without previous systemic treatment OR
• has failed to respond to \< or = 4 cycles of neoadjuvant anthracycline based therapy as assessed by clinical exam or imaging studies (mammogram, ultrasound or breast MRI).
• Patient's tumor must be classified as clinically stage T2, T3, or T4 with any N (NX, N0, N1, N2, or N3) prior to any neoadjuvant treatment.
• Patient must have an ECOG Performance Status of \< or = 1.
• Patient must have adequate organ function defined as:
• Renal Function:
• CrCl ≥ 60 ml/min for patients receiving cisplatin
• CrCl ≥ 30 ml/min for patients receiving carboplatin.
• Liver Function:
• ALT, AST, ALK Phos \< or = 1.5 x upper limit of institutional normal.
• Bilirubin \< or = 1.5 x upper limit of institutional normal.
• Normal left ventricular function (LVEF \> 50%) by MUGA or ECHO.

You may not qualify if:

• Patient must not have evidence of distant metastasis present by CT, bone scan, or PET-CT. If the bone scan or CT scans demonstrate indeterminate lesions, the nature of these lesions should be further clarified by additional testing such as PET or MRI at the discretion of the treating physician.
• Patients having received neoadjuvant anthracycline based therapy must undergo restaging to exclude distant metastases prior to enrollment.
• Patient must not have had any prior malignancies with the exception of curatively treated basal or squamous carcinoma of the skin or history of previous malignancies, treated with at least greater than 5 years disease free survival.
• Patient's tumor must not express the following biomarkers or must have Allred score \< 4 for: estrogen receptor, progesterone receptor, and is not Her2/neu amplified.
• Women of child bearing potential may not be currently pregnant or breastfeeding at time of registration and must agree to use adequate contraception.
• Patient must have \> or = grade 2 peripheral neuropathy.
• Patient must have a known hearing impairment (hearing loss or severe tinnitus). Hearing test will be performed at the discretion of the treating physician.
• Patient must not have been previously treated with cisplatin or carboplatin for any condition.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007 Mar;8(3):235-44. doi: 10.1016/S1470-2045(07)70074-8.

  PMID: 17329194 BACKGROUND

• Garber, J., Richardson, A., Harris, L., Miron, A., Silver, D., Golshan, M., Ryan, P., Ganesan, S., Wang, Z., Clarke, K., Inglehart, J., and Winer, E. Neoadjuvant cisplatin in triple negative breast cancer. SABCS, 2006.

  BACKGROUND

• Bollet MA, Sigal-Zafrani B, Gambotti L, Extra JM, Meunier M, Nos C, Dendale R, Campana F, Kirova YM, Dieras V, Fourquet A; Institut Curie Breast Cancer Study Group. Pathological response to preoperative concurrent chemo-radiotherapy for breast cancer: results of a phase II study. Eur J Cancer. 2006 Sep;42(14):2286-95. doi: 10.1016/j.ejca.2006.03.026. Epub 2006 Aug 8.

  PMID: 16893641 BACKGROUND

• Formenti SC, Volm M, Skinner KA, Spicer D, Cohen D, Perez E, Bettini AC, Groshen S, Gee C, Florentine B, Press M, Danenberg P, Muggia F. Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: a phase I/II trial. J Clin Oncol. 2003 Mar 1;21(5):864-70. doi: 10.1200/JCO.2003.06.132.

  PMID: 12610186 BACKGROUND

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cisplatin; Carboplatin; Radiotherapy; Mastectomy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Therapeutics; Surgical Procedures, Operative

Results Point of Contact

• Title: Rebecca Aft, M.D., Ph.D.
• Organization: Washington University School of Medicine

aftr@wustl.edu

314-747-0063

Study Officials

• Rebecca Aft, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2010
• First Posted: July 22, 2010
• Study Start: February 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: September 1, 2016
• Last Updated: December 30, 2016
• Results First Posted: October 28, 2016

Record last verified: 2016-11

Locations

US (1)