A Study of Whole Brain Radiation Therapy and Capecitabine in Breast Cancer Participants With Newly Diagnosed Brain Metastasis

NCT00977379 | Terminated Phase 2 Results

• 2 other identifiers: ML218732008-007349-30
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 16

Brief Summary

This open-label, randomized, parallel arm study will evaluate the effect of capecitabine administered concurrently with WBRT and as maintenance therapy in participants with breast cancer and newly diagnosed brain metastases. Participants will be randomized to receive either capecitabine with 10 days standard WBRT, or WBRT alone. Maintenance therapy will follow with capecitabine or another systemic therapy in the WBRT only group.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Best Objective Central Nervous System (CNS) Response, Assessed by Centralized Independent Expert According to Magnetic Resonance Imaging (MRI) - Intent-to-Treat (ITT) Population

  Best objective CNS response was defined as having complete response (CR) or partial response (PR) for CNS metastasis, assessed by contrast-enhanced MRI using response evaluation criteria in solid tumors (RECIST). CR: disappearance of all CNS lesions. PR: greater than or equal to (\>/=) 30 percent (%) decrease in sum of longest diameters (LD) of CNS lesions taking as reference the baseline sum LD.

  Baseline until disease progression (PD), unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall)

• Percentage of Participants With Best Objective CNS Response, Assessed by Centralized Independent Expert According to MRI - Per-Protocol (PP) Population

  Best objective CNS response was defined as having CR or PR for CNS metastasis, assessed by contrast-enhanced MRI using RECIST. CR: disappearance of all CNS lesions. PR: \>/=30% decrease in sum of LD of CNS lesions taking as reference the baseline sum LD.

  Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall)

Secondary Outcomes (13)

• Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI

  Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first up to 4 weeks after completion of WBRT (up to approximately 7 weeks)

• Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI

  Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall)

• Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI in 3 Dimension

  Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first up to 4 weeks after completion of WBRT (up to approximately 7 weeks)

• Percentage of Participants With Clinical Benefit, Assessed by Investigator According to MRI

  Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall)

• Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to MRI

  Baseline until PD, unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first up to 4 weeks after completion of WBRT (up to approximately 7 weeks)

Study Arms (2)

WBRT Followed by Standard of Care

ACTIVE COMPARATOR

Participants will receive 3000 centi-Gray (cGy) WBRT in 10 single daily fractions over 12 to 14 days (300 cGy / fraction) followed by standard of care therapy at the discretion of the treating oncologist starting no earlier than 2 weeks after completion of WBRT. The participants will be followed during the treatment until the halting of standard of care for any reason (central nervous system \[CNS\] or extra-cranial tumor progression, unacceptable toxicity, change of therapeutic strategy, withdrawal of participant consent, or death).

Radiation: WBRT; Drug: Standard of Care

WBRT+Capecitabine Followed by Capecitabine Maintenance

EXPERIMENTAL

Participants will receive 3000 cGy WBRT in 10 single daily fractions over 12 to 14 days (300 cGy / fraction) concurrent with capecitabine 825 milligrams per square meter (mg/m\^2) orally twice daily, Days 1-14 of a 21 day cycle for 1 cycle followed by capecitabine 1000 mg/m\^2 orally twice daily Days 1-14 every 21 days starting with Cycle 2, one week after completion of WBRT and continuing until the halting of capecitabine for any reason (CNS or extra-cranial progression, unacceptable toxicity, withdrawal of participant consent or death).

Radiation: WBRT; Drug: Capecitabine

Interventions

WBRT RADIATION

3000 cGy WBRT in 10 single daily fractions over 12 to 14 days (300 cGy / fraction).

WBRT Followed by Standard of Care; WBRT+Capecitabine Followed by Capecitabine Maintenance

Capecitabine DRUG

825 mg/m\^2 orally twice daily, Days 1-14 of a 21 day cycle for 1 cycle followed by 1000 mg/m\^2 orally twice daily Days 1-14 every 21 days starting with Cycle 2.

Also known as: Xeloda

WBRT+Capecitabine Followed by Capecitabine Maintenance

Standard of Care DRUG

The choice of standard of care will be at the discretion of the treating oncologist. The protocol does not specify any particular standard of care treatment.

WBRT Followed by Standard of Care

Eligibility Criteria

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

You may qualify if:

• Women with histologically confirmed breast cancer with known human epidermal receptor-2 (HER2) and hormone status
• Newly diagnosed CNS metastasis with at least one brain lesion measuring greater than or equal to (\>/=) 1 centimeter (cm) or two lesions measuring \>/= 0.5 to less than (\<) 1 cm in longest dimension
• Participant not eligible for or refusing surgery or stereotactic radiosurgery
• Eastern cooperative oncology group (EOCG) performance status 0 to 2

You may not qualify if:

• Prior treatment of brain metastases
• Leptomeningeal disease
• Known contra-indication to radiotherapy or magnetic resonance imaging (MRI) or capecitabine

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (16)

Unknown Facility

Arras, 62000, France

Location

Unknown Facility

Beuvry, 62660, France

Location

Unknown Facility

Béziers, 34500, France

Location

Unknown Facility

Bobigny, 93009, France

Location

Unknown Facility

Dijon, 21079, France

Location

Unknown Facility

Le Mans, 72015, France

Location

Unknown Facility

Lille, 59020, France

Location

Unknown Facility

Lyon, 69373, France

Location

Unknown Facility

Montpellier, 34928, France

Location

Unknown Facility

Nantes, 44202, France

Location

Unknown Facility

Narbonne, 11780, France

Location

Unknown Facility

Nice, 06000, France

Location

Unknown Facility

Paris, 75475, France

Location

Unknown Facility

Paris, 75651, France

Location

Unknown Facility

Rouen, 76000, France

Location

Unknown Facility

Salouël, 80480, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Capecitabine; Standard of Care

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; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Study was prematurely terminated due to an insufficient number of participants enrolled and therefore results are only based on a small sample of breast cancer participants with newly diagnosed brain metastasis and should be considered with caution.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2009
• First Posted: September 15, 2009
• Study Start: August 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: November 15, 2016
• Results First Posted: November 15, 2016

Record last verified: 2016-09

Locations

FR (16)