The Efficacy and Safety of Pegylated Liposomal Doxorubicin Compared With Capecitabine as First Line Chemotherapy for Metastatic Breast Cancer (P04445/MK-2746-071)

NCT00266799 | Completed Phase 3 Results

• 1 other identifier: P04445
• Study Type: interventional
• Target: 210
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, multinational, randomized, multicenter trial designed to compare pegylated liposomal doxorubicin with capecitabine as first line chemotherapy of metastatic breast cancer. The primary objective of the study is to compare the time to disease progression, although overall response rates, overall survival, quality of life, time to treatment failure, and safety and tolerability will also be assessed.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Time to Disease Progression (TTP) Using Response Evaluation Criteria in Solid Tumors (RECIST)

  TTP was defined as the time from onset of treatment with study drug until first evidence/diagnosis of progressive disease or - in the absence of any diagnosis of progressive disease - until the participant´s death. Diagnosis of progressive disease was done according to RECIST (Version 1.0) and/or investigator assessment based on RECIST. RECIST criteria used changes in the largest diameter of target/non-target lesions. Target (measurable) lesions were up to a maximum of 5 per organ \& \>20 mm by clinical imaging (\>=10 mm with spiral CT scan). Non-target lesions were all other lesions.

  From Day 1 (Cycle 1) until First Evidence/Diagnosis of Progressive Disease or Death

Secondary Outcomes (4)

• Number of Participants With an Overall Response (Complete Response [CR] + Partial Response [PR]) Between PLD and Capecitabine Treatment Groups

  From Day 1 (Cycle 1) until First Evidence/Diagnosis of Progressive Disease or Death

• Overall Survival Time in the PLD and Capecitabine Treatment Groups

  From Day 1 (Cycle 1) until Death

• Time to Treatment Failure in the PLD and the Capecitabine Treatment Groups

  From Day 1 (Cycle 1) until End of Treatment

• Quality of Life (QoL) Measured by QoL Questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) + Subjective Significance Questionnaire (SSQ))

  From Screening to Day 1 of every Treatment Cycle up to 12 Cycles

Study Arms (2)

Pegylated liposomal doxorubicin

EXPERIMENTAL

Drug: Pegylated liposomal doxorubicin (SCH 200746)

Capecitabine

ACTIVE COMPARATOR

Drug: Capecitabine

Interventions

Pegylated liposomal doxorubicin (SCH 200746) DRUG

pegylated liposomal doxorubicin (50 mg/m\^2 q 28 days) was administered intravenously until disease progression or unacceptable toxicity

Pegylated liposomal doxorubicin

Capecitabine DRUG

capecitabine (1250 mg/m\^2 BID x 14 days q 21 days) in tablets of 150 mg and 500 mg was administered orally, until disease progression or unacceptable toxicity

Capecitabine

Eligibility Criteria

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

You may qualify if:

• Patients must be female.
• Patients must have metastatic disease of a cytological or histological confirmed breast cancer.
• Patients must be 18 years or older.
• Patients should have evaluable disease (at least uni-dimensionally measurable lesion according to the RECIST criteria in at least one site that has not been irradiated), however, patients who only have non-measurable/evaluable disease are not excluded. Also patients with only bone metastasis are not excluded.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) 0-2.
• Patients must have a sufficient life expectancy to be treated with chemotherapy.
• Patients must be willing and able to complete study questionnaires.
• Patients must have adequate renal function as evidenced by serum creatinine \<=1.5 mg/dL, or a creatinine clearance of \>=45 mL/min (if serum creatinine is \> 1.5 mg/dL but \<= 1.8 mg/dL).
• Patients must have adequate bone marrow function as evidenced by leukocyte count greater than 3.5 g/L, hemoglobin \>=9.0 g/dL, and platelet count \>=100x10\^9/L.
• Patients must have adequate liver function as evidenced by bilirubin of \<=1.5 times the upper limits of normal (ULN) and alkaline phosphatase \<=3 times, ULN unless related to liver metastasis.
• Patients must have Sodium and Potassium values within normal limits.
• Patients whose clinical condition (co-morbidity) allows a treatment with monotherapy or who expressed their wish to be treated with monotherapy.
• Patients must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

You may not qualify if:

• History of receiving prior chemotherapy in the metastatic setting (Note: patients may have had
• hormonal therapy or chemotherapy in the adjuvant setting; patients may have received hormonal therapy in metastatic setting, patients may have received local radiotherapy).
• Patients with positive estrogen- / progesterone-receptor status, where an endocrine therapy is indicated. However, patients progressing under hormonal therapy are not excluded.
• Patients with known hypersensitivity to doxorubicinhydrochlorid or to any of the excipients OR known hypersensitivity to capecitabine or fluorouracil or to any of the excipients.
• Patients with known DPD (dihydro pyrimidine dehydrogenase) deficiency.
• Patients who are receiving a concomitant treatment with sorivudine or its chemically related analogues, such as brivudine.
• Patients who are taking concomitant medications (except bisphosphonates) for metastatic disease, including hormonal therapy, radiation therapy, trastuzumab, or biologicals are also not permitted.
• Patients with Human epidermal growth factor receptor 2 (Her-2/neu) overexpressing tumors with the most recent evaluation as the relevant result
• immunologically Her2neu 3+ positive
• Her2neu-2+ positive and ´Fluorescent in-situ hybridization (FISH)´ positive
• History of treatment with capecitabine
• History of treatment with anthracyclines in the adjuvant setting exceeding cumulative doses of anthracyclines by more than 360 mg/m\^2 doxorubicin (or equivalents, i.e. 600mg/m\^2 epirubicine).
• Patients with anthracycline resistant disease are not permitted. Anthracycline resistance is defined as development of locally recurrent or metastatic disease while on adjuvant anthracycline therapy, or relapse less than 12 months after completion of anthracycline therapy.
• Strong remission pressure that requires polychemotherapy with the exception of patients who are not suitable for a treatment with polychemotherapy or not accepting polychemotherapy.
• Evidence of primary or metastatic malignancy involving the central nervous system unless previously treated and asymptomatic for 3 months or greater.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Essex Pharma GmbH: collaborator

Related Publications (1)

• Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

  PMID: 34037241 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

liposomal doxorubicin; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2005
• First Posted: December 19, 2005
• Study Start: January 13, 2006
• Primary Completion: September 29, 2010
• Study Completion: October 18, 2010
• Last Updated: June 8, 2017
• Results First Posted: November 16, 2011

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share