Second-line Endocrine Treatment Followed by Capecitabine Versus Capecitabine Followed by Endocrine Treatment in Patients With Metastatic ER Positive Breast Cancer

Randomized Phase II/III Study of Second-line Endocrine Treatment Followed by Capecitabine Versus Capecitabine Followed by Endocrine Treatment in Patients With Metastatic Estrogen Receptor Positive Breast Cancer

This trial studies the effects on quality of life and on time to second progression of the sequence endocrine therapy-capecitabine versus the sequence capecitabine-endocrine treatment. It is anticipated that the time on study (which is the time between randomization and the discontinuation of the second treatment in the sequence) will be similar for both arms of the study. The quality of life during this period, however, could be better in the patient group receiving the most effective first agent in the sequence. If this proves to be true, the conventional wisdom that endocrine therapy should be continued until no further endocrine options remain, must be abandoned.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: capecitabine; Drug: hormonal treatment (tamoxifen, exemestane, anastrozole or letrozole)

Detailed Description

This is a randomized phase II/II study. Patients are randomized for the sequence capecitabine-hormonal therapy versus hormonal therapy- capecitabine. At progression the patient should receive the other protocol treatment (e.g. if the patient was randomized to capecitabine, at progression the treatment should be switched to hormonal treatment).

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • NKI-AVL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Written informed consent.
2. Proven infiltrating breast cancer with distant metastases or inoperable locally advanced disease.
3. Positive estrogen receptor (≥ 10% positive nuclei at immunohistochemistry). Progesterone and HER-2 neu receptor have to be known.
4. - Progressive disease during first line hormonal therapy (either tamoxifen or aromatase inhibitor) for metastatic or inoperable locally advanced disease. Simultaneous use of LH-RH analogs is allowed. OR - Recurrence of disease (M1) during adjuvant hormonal therapy (either tamoxifen or aromatase inhibitor).
5. No prior chemotherapy for metastatic disease
6. Willing and able to participate in Quality of Life investigation -

Exclusion Criteria:

1. Other malignancy except carcinoma in situ, unless the other malignancy was treated 5 or more years ago with curative intent without the use of chemotherapy or radiation therapy.
2. Pregnancy or breast feeding women.
3. Contra-indications to the use of capecitabine
4. Known CNS metastases

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; capecitabine followed by hormonal treatment	Drug: capecitabine; 200 mg, BID, PO, QD until progression of disease; Drug: hormonal treatment (tamoxifen, exemestane, anastrozole or letrozole); either tamoxifen or aromatase inhibitor (exemestane, anastrozole or letrozole), QD, until progression of disease
Active Comparator: 2; hormonal treatment followed by capecitabine	Drug: capecitabine; 200 mg, BID, PO, QD until progression of disease; Drug: hormonal treatment (tamoxifen, exemestane, anastrozole or letrozole); either tamoxifen or aromatase inhibitor (exemestane, anastrozole or letrozole), QD, until progression of disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Quality of life during the study period: Physical functioning scale of the QLQ-C30; Global Health status/QoL of the QLQ-C30	every 6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to second progression and quality of life adjusted time to 2nd recurrence.	at the end of the study

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: May 22, 2008
• First Submitted That Met QC Criteria: May 23, 2008
• First Posted (Estimate): May 26, 2008

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 13, 2017
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: metastatic; ER positive; PD during/after first line hormonal treatment
• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Capecitabine; Letrozole; Tamoxifen; Anastrozole; Exemestane
• Other Study ID Numbers: N07MAN; Eudract 2007-007030-20