Neoadjuvant Platinum-based Chemoradiation Therapy for Loc... | NCT01167192

NCT01167192

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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)

Name	Type	Description	Arm Group Labels	Other Names
Cisplatin	Drug		Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation
Carboplatin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.	Up to 5 years from registration

Eligibility Module

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.

Name	Affiliation	Role
Rebecca Aft, M.D., Ph.D.	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Washington University School of Medicine		St Louis	Missouri	63110	United States

PubMed Identifier	Type	Citation
17329194	Background	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.
	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.
16893641

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

ID	Title	Description
FG000	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation	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/m^2 and cyclophosphamide 600 mg/m^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m^2 for 14 days for 4 cycles)

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation	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/m^2 and cyclophosphamide 600 mg/m^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m^2 for 14 days for 4 cycles)

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

1 patient was removed from study due to treatment related toxicity prior to efficacy evaluation and 1 patient expired prior to efficacy evaluation. These two patients are not included in this outcome measure.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation	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/m^2 and cyclophosphamide 600 mg/m^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m^2 for 14 days for 4 cycles)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation	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/m^2 and cyclophosphamide 600 mg/m^2 for 14 days for 4 cycles followed by paclitaxel 175 mg/m^2 for 14 days for 4 cycles)

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases

ID	Term
D002945	Cisplatin
D016190	Carboplatin
D011878	Radiotherapy
D008408	Mastectomy

ID	Term
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds