Trial to Evaluate Genomic Expression Profiles to Direct Preoperative Chemotherapy in Early Stage Breast Cancer

NCT00636441 | Terminated Phase 2 Results

• 3 other identifiers: Pro00001345W81XWH-07-1-0394BC060228-W81XWH-07-1-0394
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This multi-center randomized Phase II study assigned HER2-negative early-stage breast cancer patients to receive preoperative systemic chemotherapy in either a "genomic-guided" arm or a "non-guided arm." The "genomic-guided" method (Arm 1) used genomic expression profiling to assign the preoperative therapy (Doxorubicin/Cyclophosphamide (AC) versus Docetaxel/Cyclophosphamide (TC), while Arm 2 used random assignment to these two therapies.

Conditions

Early-Stage Breast Cancer

Keywords

Early-Stage Breast Cancer; Preoperative systemic chemotherapy (PST); Genomic; Genomic Predictor; Genomic Expression Profiles; Randomized; Pathologic complete response (pCR); HER2 negative; Doxorubicin and docetaxel; Doxorubicin and cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR) Rate in Patients With HER2-negative Early-stage Breast Cancer

  Pathological complete response (pCR) was defined as the disappearance of all invasive disease in the breast or if only residual in situ or lymph node disease is found. The pCR rate is presented with its 95% confidence interval for the Guided and Non-guided arms.

  4-5 weeks after the fourth cycle of chemotherapy; approximately 16-17 weeks

Secondary Outcomes (9)

• Probabilities of Being Sensitive to AC and TC as Determined by the Patient's Genomic Signatures

  10 years

• Percentage of Patients Who Had Breast-conserving Surgery With Negative Margins

  6 months

• To Percentage of Patients Who Had Breast-conserving Surgery at First Attempt.

  6 months

• Clinical Response Using WHO Criteria

  12 weeks, 2-3 weeks after the fourth cycle of chemotherapy

• Disease-free Survival

  2 years

Study Arms (2)

Guided Arm

ACTIVE COMPARATOR

Genomically-guided treatment allocation. This arm has the following cohorts: * AC sensitive patients \[\>60% probability of response to AC\] * TC sensitive patients \[\>60% probability of response to TC\] * Patients sensitive to neither AC nor TC; randomized to AC or TC

Drug: Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC)

Non-Guided Arm

ACTIVE COMPARATOR

Non-genomically-guided treatment allocation. This arm has the following cohorts: * In patients randomly assigned to AC: * Patients sensitive to AC * Patients sensitive to TC * Patients sensitive to neither AC nor TC * In patients randomly assigned to TC: * Patients sensitive to AC * Patients sensitive to TC * Patients sensitive to neither AC nor TC

Drug: Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC)

Interventions

Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC) DRUG

Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² (AC) or Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² (TC) every 3 weeks for 4 cycles as neoadjuvant therapy

Also known as: Adriamycin (Doxorubicin), Rubex (Doxorubicin), Taxotere (Docetaxel), Cytoxan (Cyclophosphamide)

Guided Arm; Non-Guided Arm

Eligibility Criteria

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

You may qualify if:

• Histologic Documentation: Patients must have a histologic (i.e., not just cytologic) diagnosis of invasive breast cancer by core biopsy. Excisional biopsy or incisional biopsy is not allowed. All breast cancer histologic types are allowed.
• Stage: Any patient with a clinical T1c (\>1.5 cm) to T3 invasive breast cancer by the revised TNM staging system (AJCC 6th edition) will be eligible. Any N stage disease is allowed. No distant metastases allowed.
• Tumor Site: Patients must have invasive cancer in the breast. Multifocal disease (i.e. confined to a single quadrant in the same breast) is allowed. Multicentric disease (i.e. disease in multiple breast quadrants) is not allowed. Determination of multifocal and multicentric disease status will be made by the evaluating surgeon; ambiguous cases will be reviewed by the principal investigator. Patients with synchronous contralateral invasive breast cancers are not eligible; prior contralateral breast cancer allowed as long as patient has not received prior chemotherapy or radiation therapy in the past 5 years.
• Measurable Disease: Patients must have measurable disease in the breast by imaging studies (mammogram, ultrasound, or MRI), and must be greater than 1.5 cm in at least one dimension by one or more of the imaging assessments.
• Conventional Biomarker Status: Standard clinical biomarkers for ER, PR, and HER2 must be obtained on the initial diagnostic core biopsy. The invasive cancer must be HER2 negative (i.e. immunohistochemistry score 1-2+ and/or FISH non-amplified). Any ER/PR status is allowed. Patients who are HER2 2+ on initial immunohistochemistry assessment will be further assessed by FISH. In this instance, patient will be consented and further screened for eligibility and have tissue acquired for genomic profiling. If the standard of care additional FISH testing is positive for HER2 gene amplification, the patient will not be randomized and will be treated in the same manner as screen failures.
• Must be deemed a surgical candidate.
• Fresh tissue biopsy material must be available for genomics analysis.
• No prior chemotherapy, radiotherapy, or biologic/targeted therapy for the currently diagnosed breast cancer, or any other malignancy in the past 5 years, is allowed. No prior anthracycline or taxane therapy.
• Prior malignancies are allowed if the patient is considered to be disease-free for 5 or more years and is deemed to be at low risk for recurrence. Patients with any prior diagnosis of in situ malignancies (melanoma, bladder, colon, cervical, basal cell, or squamous carcinoma) are eligible regardless of time from diagnosis.
• Aged at least 18 years.
• ECOG Performance Status 0-1.
• Adequate Organ Function:
• Total bilirubin ≤1.0 x the institutional ULN
• Hepatic enzymes (AST (SGOT), ALT (SGPT)) ≤1.5x the institutional ULN
• Alkaline Phosphatase ≤2.5 x ULN

You may not qualify if:

• \. Patients who have received investigational drugs within 4 weeks prior to starting study drug and/or who have not recovered from side effects of such therapy are not eligible.

Sponsors & Collaborators

• Duke University: lead
• United States Department of Defense: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Potti A, Dressman HK, Bild A, Riedel RF, Chan G, Sayer R, Cragun J, Cottrill H, Kelley MJ, Petersen R, Harpole D, Marks J, Berchuck A, Ginsburg GS, Febbo P, Lancaster J, Nevins JR. Genomic signatures to guide the use of chemotherapeutics. Nat Med. 2006 Nov;12(11):1294-300. doi: 10.1038/nm1491. Epub 2006 Oct 22.

  PMID: 17057710 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Pathologic Complete Response

Interventions

Doxorubicin; Cyclophosphamide; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: P. Kelly Marcom, M.D.
• Organization: Duke University Medical Center

marco001@mc.duke.edu

919-684-3877

Study Officials

• Paul K Marcom, MD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2008
• First Posted: March 14, 2008
• Study Start: April 1, 2008
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: December 11, 2015
• Results First Posted: October 7, 2014

Record last verified: 2014-10

Locations

US (1)