Caelyx, Cyclophosphamide and Herceptin in Patients With Metastatic Breast Cancer

Phase IV/II Trial With the Combination of Pegylated Liposomal Doxorubicin (Caelyx), Cyclophosphamide and Trastuzumab in Patients With Metastatic Breast Cancer With Overexpression of Human Epidermal Growth Factor Receptor 2 (HER2)/Neu

Eligible patients must receive Caelyx plus Cyclophosphamide plus Herceptin for 6 cycles that will be administered every 4 weeks.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Trastuzumab; Drug: Liposomal Doxorubicin

Detailed Description

Sample size calculation will be done by means of Simon's method in 2 stages for phase II studies and will be based on the principal aim of the study (evaluation of the rate of objective response).

The hypothesis brings over of the efficiency of the treatment it will be accepted if a rate of objective response of at least 55 % is obtained, rejecting the efficiency of the treatment when the rate of response targets be lower than 35 %. In this case, considering an alpha error of 0.05 and 80 % power, 14 patients will be included in the first stage; the study would continue if more than 5 objective responses were found. The total number of patients to including in the study would be 44. The results will be significant if they find at least 20 objective responses.

Assuming a drop-out rate of 10 %, the total number of patients needed is 49 patients.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Cadiz, Spain, 11009
    • Hospital Puerta del Mar
  • Castelló, Spain, 12002
    • Hospital Provincial de Castellon
  • Jaén, Spain, 23007
    • Complejo Hospitalario de Jaén
  • La Coruña, Spain, 15006
    • Hospital Juan Canalejo
  • La Coruña, Spain, 15009
    • Centro Oncologico Regional de Galicia
  • Lugo, Spain, 27004
    • Hospital Xeral Calde de Lugo
  • MAdrid, Spain, 28021
    • Hospital Universitario Doce de Octubre
  • MAdrid, Spain, 28040
    • Hospital Clinico Universitario San Carlos
  • Santa Cruz De Tenerife, Spain, 38010
    • Hospital Nuestra Señora de Candelaria
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trías i Pujol
  • MAdrid
    • Alcorcón, MAdrid, Spain, 28922
      • Fundacion Hospital Alcorcon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients must sign an informed consent before of specific procedures of clinical trial.
• Patients with histologically confirmed breast cancer and overexpression of Her2neu.
• Age> 18 years.
• Eastern Cooperative Oncology Group (ECOG) equal or < 2.
• Patients have not been treated previously with chemotherapy for metastatic disease.
• Patients must have at least one measurable lesion according to RECIST criteria.
• Patients should have an adequate organ function to tolerate chemotherapy.

Exclusion Criteria:

• Patients with hypersensitivity reactions to any of the medications of the clinical trial.
• Patients who are pregnant or lactating are not eligible.
• Hepatic disease.
• Not controlled active infection
• Symptomatic metastatic brain cancer
• Previous adjuvant treatment with anthracyclines with a total accumulated dose > 300 mg/m2 (Doxorubicin) or > 600 mg/m2 (Epirubicin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Caelyx,Cyclophosphamide,Trastuzumab; Caelyx (Liposomal Doxorubicin) 50 mg/m2 every 4 weeks for 6 cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for 6 cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg)	Drug: Cyclophosphamide; Other Names: Cytoxan; Drug: Trastuzumab; Other Names: Herceptin; Drug: Liposomal Doxorubicin; Other Names: Caelyx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is the sum of the Complete Responses (CR) and Partial Responses (PR) according to the RECIST criteria, experienced for each patient during treatment (recorded from the start of the treatment until disease progression). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan (computed tomography) or MRI (magnetic resonance imaging): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = CR + PR.	Up to cycle 6 (24 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression (TTP)	TTP was defined as the time elapsed from first treatment until clinical evidence of disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	Through study treatment, and follow up period, assessed up to 88 weeks
Time to Treatment Failure (TTF)	TTF was defined as the time elapsed from first treatment until patient discontinuation due to toxicity, disease progression, death or withdrawal of consent for any reason, whichever occurred first.	Through study treatment, and follow up period, assessed up to 88 weeks
Response Duration	Response duration was defined as the time elapsed from the first evidence of tumor response (Complete response or Partial Response) until clinical evidence of disease progression or death occurred.	Through study treatment, and follow up period, assessed up to 88 weeks
Overall Survival (OS)	OS was defined as the time elapsed from first treatment until death from any cause.	Through study treatment, and follow up period, assessed up to 88 weeks

Collaborators and Investigators

• Sponsor: Spanish Breast Cancer Research Group
• Collaborators: Schering-Plough

Publications and helpful links

General Publications

• Martin M, Sanchez-Rovira P, Munoz M, Baena-Canada JM, Mel JR, Margeli M, Ramos M, Martinez E, Garcia-Saenz JA, Casado A, Jaen AM, Gonzalez-Farre X, Escudero MJ, Rodriguez-Martin C, Carrasco E; GEICAM. Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004-05 study. Ann Oncol. 2011 Dec;22(12):2591-2596. doi: 10.1093/annonc/mdr024. Epub 2011 Mar 17.

Helpful Links

• Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 14, 2009

Study Registration Dates

• First Submitted: November 24, 2005
• First Submitted That Met QC Criteria: November 24, 2005
• First Posted (Estimate): November 28, 2005

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Metastatic breast cancer; HER2 positive breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Trastuzumab; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: GEICAM/2004-05