Clinical trial NCT01167192: Neoadjuvant Platinum-based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer
Official title: Effect of Neoadjuvant Platinum-based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer: Clinical Outcome and Correlation to Biological Parameters
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Neoplasms
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2010-07-22
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Patient must be \> or = 18 years of age
* Patient must be female
* Patient must have primary invasive ductal breast adenocarcinoma that either:

  1. is newly diagnosed, without previous systemic treatment OR
  2. 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:

  1. Renal Function:

     1. CrCl ≥ 60 ml/min for patients receiving cisplatin
     2. CrCl ≥ 30 ml/min for patients receiving carboplatin.
  2. Liver Function:

     1. ALT, AST, ALK Phos \< or = 1.5 x upper limit of institutional normal.
     2. Bilirubin \< or = 1.5 x upper limit of institutional normal.
  3. Normal left ventricular function (LVEF \> 50%) by MUGA or ECHO.
  4. Hematologic:

     1. Absolute Neutrophil Count \> or = 1500/mcl
     2. Platelets \> or = 100,000/mcl
     3. Hemoglobin \> or = 8.0 g/dl
* Patient must be able and willing to sign informed consent document.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR)
timeFrame: Prior to surgery (approximately 12-16 weeks from registration)
measure: Relationship Between Tumor Response and Deficiencies in DNA Repair Mechanisms
timeFrame: Prior to surgery (approximately 12-16 weeks from registration)
Secondary outcomes:
measure: Time to Disease Progression
timeFrame: Up to 5 years from registration
measure: Number of Participants With Surgical Complications
timeFrame: 30 days post surgery (approximately 16-20 weeks from registration)
measure: Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow
timeFrame: Up to 15 months from registration
measure: Overall Survival Rate
timeFrame: Median follow-up was 59.9 months
measure: Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events
timeFrame: 30 days post surgery (approximately 16-20 weeks after start of registration)
measure: Successful Development of Animal Models of Triple Negative Breast Cancers as Measured by the Ability to Grow the Tumors in Mice.
timeFrame: At the time of IVAD placement and at the time of surgery
measure: Successful Development of Animal Models for Triple Negative Breast Cancers as Measured by the Ability to Passage the Tumors in Mice
timeFrame: At the time of IVAD placement and at the time of surgery
measure: Successful Development of Animal Models in Triple Negative Breast Cancers as Measured by the Ability of the Tumors to Metastasize to Other Organs
timeFrame: At the time of IVAD placement and at the time of surgery
measure: Successful Development of Animal Models of Triple Negative Breast Cancer as Measured by the Genetic Similarity Between the Primary Tumor and the Tumor in Animals
timeFrame: At the time of IVAD placement and at the time of surgery
measure: Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and the Correlation to Tumor Response
timeFrame: Up to 15 months from time of registration
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Rebecca Aft, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.