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

Phase 2

Terminated

• Conditions: Breast Neoplasms
• Interventions: Drug: Cisplatin; Drug: Carboplatin; Radiation: Radiation therapy; Procedure: Mastectomy (recommended but not mandatory)

• Registration Number: NCT01167192
• Lead Sponsor: Washington University School of Medicine

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2010-07-14
• Study First Submitted QC: 2010-07-19
• Study First Posted: 2010-07-22
• Study Start: 2011-02
• Primary Completion: 2012-08
• Study Completion: 2016-09
• Results First Submitted: 2016-09-08
• Results First Submitted QC: 2016-09-08
• Results First Posted: 2016-10-28
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-09
• Last Update Posted: 2016-12-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 10

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation	Radiation therapy	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)
Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation	Mastectomy (recommended but not mandatory)	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)
Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation	Cisplatin	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)
Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation	Carboplatin	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)

Primary Outcome Measures

Name	Time	Method
Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR)	Prior to surgery (approximately 12-16 weeks from registration)	* 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
Relationship Between Tumor Response and Deficiencies in DNA Repair Mechanisms	Prior to surgery (approximately 12-16 weeks from registration)

Secondary Outcome Measures

Name	Time	Method
Time to Disease Progression	Up to 5 years from registration	Progression = at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, unequivocal progression of existing non-target lesions.
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
Successful Development of Animal Models of Triple Negative Breast Cancers as Measured by the Ability to Grow the Tumors in Mice.	At the time of IVAD placement and at the time of surgery
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	At the time of IVAD placement and at the time of surgery
Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and the Correlation to Tumor Response	Up to 15 months from time of registration
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)
Successful Development of Animal Models for Triple Negative Breast Cancers as Measured by the Ability to Passage the Tumors in Mice	At the time of IVAD placement and at the time of surgery
Successful Development of Animal Models in Triple Negative Breast Cancers as Measured by the Ability of the Tumors to Metastasize to Other Organs	At the time of IVAD placement and at the time of surgery

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 St. Louis, Missouri, United States