Preoperative Treatment of Breast Cancer With Two Different Sequential Treatment Regimens

A Randomized Phase 2 Trial of Doxorubicin Plus Pemetrexed Followed by Docetaxel, Versus Doxorubicin Plus Cyclophosphamide Followed by Docetaxel, as Neoadjuvant Treatment for Early Breast Cancer

An open-label randomized Phase II study in order to explore two different sequential anthracycline-based neoadjuvant treatment regimens in female patients with primary, operable breast cancer (T2-T4/N0-2/M0).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: pemetrexed; Drug: doxorubicin; Drug: docetaxel; Drug: cyclophosphamide

• Study Type: Interventional
• Enrollment (Actual): 257
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Baden-Baden, Germany, 76532
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Berlin, Germany, 10967
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Hamburg, Germany, 20357
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Heidelberg, Germany, D-69115
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Italy
  • Cremona, Italy, 26100
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Rozzano, Italy, 20089
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Russian Federation
  • Moscow, Russian Federation, 129128
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Saint Petersburg, Russian Federation, 197022
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Spain
  • Jaen, Spain, 23007
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Sabadell, Spain, 08208
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Valencia, Spain, 46010
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of primary early breast cancer, tumor size greater than or equal to 2 centimeters (cm), of Stages T2-T4/N0-2.
• Performance status 0-2 Eastern Cooperative Oncology Group (ECOG).
• Adequate organ function (bone marrow, hepatic, renal, cardiac).

Exclusion Criteria:

• Prior anthracyclines as part of prior anticancer therapy.
• Concurrent antitumor therapy.
• Second primary malignancy.
• Serious concomitant systemic disorder.

• Pre-existing sensorial or motor neuropathy

  • Grade 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A: Pemetrexed Plus Doxorubicin, Followed by Docetaxel	Drug: pemetrexed; 500 mg/m^2, intravenous (IV), every 21 days, 4 cycles (1-4); Other Names: LY231514, Alimta; Drug: doxorubicin; 60 mg/m^2, intravenous (IV), every 21 days, 4 cycles (1-4); Drug: docetaxel; 100 mg/m^2, intravenous (IV), every 21 days, 4 cycles (5-8)
Active Comparator: B: Cyclophosphamide Plus Doxorubicin, Followed by Docetaxel	Drug: doxorubicin; 60 mg/m^2, intravenous (IV), every 21 days, 4 cycles (1-4); Drug: docetaxel; 100 mg/m^2, intravenous (IV), every 21 days, 4 cycles (5-8); Drug: cyclophosphamide; 600 mg/m2, intravenous (IV), every 21 days, 4 cycles (1-4)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Pathological Complete Response	pathological assessment of tissue removed during surgery to determine if tumor tissue is still present after chemotherapy	surgery after eight 21-day cycles of chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Clinical Tumor Response After the First Sequence of Chemotherapy	The number of participants with a clinical tumor response based on measurement of tumor size after the first sequence of chemotherapy, without a second confirmatory tumor measurement, per protocol.	Cycles 1-4 (21-day cycles)
Number of Participants With a Clinical Tumor Response After the Second Sequence of Chemotherapy	The number of participants with a clinical tumor response based on measurement of tumor size after the second sequence of chemotherapy, without a second confirmatory tumor measurement required, per protocol.	Cycles 5-8 (21-day cycles)
Number of Patients With Histologically Negative Axillary Lymph Node Status at Surgery	Histologically negative is defined as no malignant cells present in the axillary lymph nodes during surgery.	surgery after eight 21-day cycles of chemotherapy
Disease-free Survival	Disease-free survival is defined as the time from date of study enrollment (randomization) to first date of progressive disease (PD) or death from any cause. PD per Response Evaluation Criteria In Solid Tumors (RECIST) criteria is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For patients not known to have died as of the data cut-off date and who do not have progressive disease, disease-free survival was censored at the last contact date.	baseline through post surgery, follow-up for 3 years post-surgery (up to 5.2 years after randomization)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Chair: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Monday-Friday 9am - 5pm Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• Schneeweiss A, Marme F, Ruiz A, Manikhas AG, Bottini A, Wolf M, Sinn HP, Mansouri K, Kennedy L, Bauknecht T. A randomized phase II trial of doxorubicin plus pemetrexed followed by docetaxel versus doxorubicin plus cyclophosphamide followed by docetaxel as neoadjuvant treatment of early breast cancer. Ann Oncol. 2011 Mar;22(3):609-617. doi: 10.1093/annonc/mdq400. Epub 2010 Aug 23.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: September 2, 2005
• First Submitted That Met QC Criteria: September 2, 2005
• First Posted (Estimate): September 8, 2005

Study Record Updates

• Last Update Posted (Estimate): March 21, 2012
• Last Update Submitted That Met QC Criteria: March 15, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Folic Acid Antagonists; Docetaxel; Cyclophosphamide; Doxorubicin; Pemetrexed
• Other Study ID Numbers: 7113; H3E-MC-S080 (Other Identifier: Eli Lilly and Company)