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

Primary Purpose

Breast Neoplasms

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Cisplatin

Carboplatin

Radiation therapy

Mastectomy (recommended but not mandatory)

About this trial

This is an interventional treatment trial for Breast Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation

Arm Description

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)

Outcomes

Primary Outcome Measures

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

Relationship Between Tumor Response and Deficiencies in DNA Repair Mechanisms

Secondary Outcome Measures

Time to Disease Progression

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

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

Overall Survival Rate

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

Successful Development of Animal Models of Triple Negative Breast Cancers as Measured by the Ability to Grow the Tumors in Mice.

Successful Development of Animal Models for Triple Negative Breast Cancers as Measured by the Ability to Passage the Tumors in Mice

Successful Development of Animal Models in Triple Negative Breast Cancers as Measured by the Ability of the Tumors to Metastasize to Other Organs

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

Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and the Correlation to Tumor Response

Full Information

NCT ID

NCT01167192

First Posted

July 14, 2010

Last Updated

November 9, 2016

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT01167192

Brief Title

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

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Terminated

Study Start Date

February 2011 (undefined)

Primary Completion Date

August 2012 (Actual)

Study Completion Date

September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Type

Radiation

Intervention Name(s)

Radiation therapy

Intervention Type

Procedure

Intervention Name(s)

Mastectomy (recommended but not mandatory)

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

Relationship Between Tumor Response and Deficiencies in DNA Repair Mechanisms

Time Frame

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

Secondary Outcome Measure Information:

Title

Time to Disease Progression

Description

Time Frame

Up to 5 years from registration

Title

Number of Participants With Surgical Complications

Time Frame

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

Title

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

Time Frame

Up to 15 months from registration

Title

Overall Survival Rate

Time Frame

Median follow-up was 59.9 months

Title

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

Time Frame

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

Title

Successful Development of Animal Models of Triple Negative Breast Cancers as Measured by the Ability to Grow the Tumors in Mice.

Time Frame

At the time of IVAD placement and at the time of surgery

Title

Successful Development of Animal Models for Triple Negative Breast Cancers as Measured by the Ability to Passage the Tumors in Mice

Time Frame

At the time of IVAD placement and at the time of surgery

Title

Successful Development of Animal Models in Triple Negative Breast Cancers as Measured by the Ability of the Tumors to Metastasize to Other Organs

Time Frame

At the time of IVAD placement and at the time of surgery

Title

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

Time Frame

At the time of IVAD placement and at the time of surgery

Title

Determine the Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and the Correlation to Tumor Response

Time Frame

Up to 15 months from time of registration

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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: 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. Hematologic: Absolute Neutrophil Count > or = 1500/mcl Platelets > or = 100,000/mcl 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rebecca Aft, M.D., Ph.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17329194

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.

Results Reference

background

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.

Results Reference

background

PubMed Identifier

16893641

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.

Results Reference

background

PubMed Identifier

12610186

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.

Results Reference

background

Links:

URL

http://www.siteman.wustl.edu

Description

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

Learn more about this trial

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

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