1st or 2nd Line MBC (Metastatic Breast Cancer) With Previous Avastin (Bevacizumab) Therapy - Full Text View

Sponsor:	Accelerated Community Oncology Research Network
Collaborator:	Onyx Pharmaceuticals
Information provided by (Responsible Party):	Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:	NCT00493636

Purpose

The study is being conducted to compare progression-free survival in patients treated with sorafenib and gemcitabine/capecitabine versus patients treated with placebo and gemcitabine/capecitabine for locally advanced or metastatic breast cancer that has progressed during or following treatment with a bevacizumab-containing regimen.

Condition	Intervention	Phase
Breast Cancer	Drug: Gemcitabine Drug: Sorafenib Drug: Placebo Drug: Capecitabine	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Double-Blind, Randomized Phase 2b Study of Sorafenib Compared to Placebo When Administered in Combination With Chemotherapy for Patients With Locally Advanced or MBC That Has Progressed During or After Bevacizumab Therapy

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Capecitabine Bevacizumab Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by Accelerated Community Oncology Research Network:

Primary Outcome Measures:

Progression Free Survival [ Time Frame: From the date of randomization to the date of first documented disease progression (i.e., the date on which a radiologic procedure or clinical evaluation was performed) or the date of death due to any cause, if before progression. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall Survival [ Time Frame: From the date of randomization to date of death due to any cause. ] [ Designated as safety issue: No ]
Time to Progression [ Time Frame: Calculated as the time (days) from date of randomization to date of first observed disease progression (radiological or clinical, whichever is earlier). ] [ Designated as safety issue: No ]
Overall Response Rate [ Time Frame: The overall tumor burden at baseline will be compared with subsequent measurements up to the date of first documented disease progression or the date of death due to any cause, if before progression. ] [ Designated as safety issue: No ]
Duration of Overall Response [ Time Frame: Period measured from the first documentation of complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease or death is objectively documented. ] [ Designated as safety issue: No ]
Treatment-Emergent AEs, Laboratory Parameters, and Vital Signs [ Time Frame: An AE is treatment emergent if it starts or worsens in severity after the first dose of study treatment. Reported AEs will be coded by MedDRA dictionary. The toxicity grade of selected lab parameters will be determined using the NCI-CTCAE, Version 3.0. ] [ Designated as safety issue: Yes ]

Enrollment:	160
Study Start Date:	June 2007
Estimated Study Completion Date:	November 2011
Estimated Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: A Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle; Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)	Drug: Gemcitabine Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle; Drug: Sorafenib Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)
Placebo Comparator: B Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle; Placebo will be administered ( 2 tablets ) orally twice daily (approximately every 12 hours)	Drug: Gemcitabine Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle; Drug: Placebo Placebo will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)
Active Comparator: C Capecitabine will be administered orally at a dose of 1,000 mg/m2 twice daily, within 30 minutes after a meal, for 14 days followed by a 7 day rest period (without capecitabine); Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)	Drug: Sorafenib Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours) Drug: Capecitabine Capecitabine will be administered orally at a dose of 1,000 mg/m2 twice daily, within 30 minutes after a meal, for 14 days followed by a 7 day rest period (without capecitabine).
Placebo Comparator: D Capecitabine will be administered orally at a dose of 1,000 mg/m2 twice daily, within 30 minutes after a meal, for 14 days followed by a 7 day rest period (without capecitabine); Placebo will be administered (2 tablets) orally twice daily (approximately every 12 hours).	Drug: Placebo Placebo will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours) Drug: Capecitabine Capecitabine will be administered orally at a dose of 1,000 mg/m2 twice daily, within 30 minutes after a meal, for 14 days followed by a 7 day rest period (without capecitabine).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the breast.
Measurable or evaluable locally advanced or metastatic disease.
Age ≥18 years.
Disease progression during or after treatment with a bevacizumab-containing regimen in the adjuvant or first-line metastatic setting.
Patients must have discontinued chemotherapy at least 3 weeks prior to randomization.
No more than one prior chemotherapy regimen for locally advanced or metastatic disease.
Prior hormonal therapy allowed provided it has been discontinued prior to randomization.
Prior radiation therapy is allowed but must be completed at least 3 weeks prior to randomization. Previously radiated area(s) must not be the only site of disease.
ECOG Performance Status of 0 or 1.
Adequate bone marrow, liver, and renal function
Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to randomization, and must agree to use adequate contraception prior to study entry, for the duration of study participation and 28 days after the last study drug dosing.
Patients must be able and willing to sign a written informed consent.
Patients must be able to swallow and retain oral medication.

Exclusion Criteria:

Patients with breast cancer over-expressing human epidermal growth factor receptor 2 (HER-2) (gene amplification by FISH or 3+ over-expression by immunohistochemistry). Patients with unknown HER-2 status are not eligible.
Patients with active brain metastases.
Major surgery, open biopsy, or significant traumatic injury within 4 weeks of randomization.
Prior use of gemcitabine/capecitabine or sorafenib.
Evidence or history of bleeding diathesis or coagulopathy.
Serious, non-healing wound, ulcer, or bone fracture.
Substance abuse, or medical, psychological, or social condition that may interfere with the patient's participation in the study or evaluation of the study results.
Use of cytochrome P450 enzyme-inducing anti-epileptic drugs is not allowed.
Clinically significant cardiac disease
Uncontrolled hypertension
Thrombolic, embolic, venous, or arterial events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
Pulmonary hemorrhage/bleeding event > NCI-CTCAE Grade 2 within 4 weeks of randomization.
Any other hemorrhage/bleeding event ≥ NCI-CTCAE Grade 3 within 4 weeks of randomization.
Active clinically serious infection > NCI-CTCAE Grade 2.
Known HIV infection or chronic hepatitis B or C (the safety and effectiveness of sorafenib in this patient population have not been studied).
Previous or concurrent cancer that is distinct in primary site or histology from breast cancer EXCEPT cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis] or any cancer curatively treated > 5 years prior to randomization.
Known or suspected allergy to sorafenib or gemcitabine/capecitabine.
Prior or concurrent use of St. John's Wort or rifampin (rifampicin) within 3 weeks of randomization.
Concurrent anti-cancer therapy other than gemcitabine/capecitabine and sorafenib/placebo.
Prior treatment with any agent that targets VEGF or VEGFR (licensed or investigational), except bevacizumab.
Women who are pregnant or breast-feeding.
Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, preceding randomization.
Inability to comply with protocol and/or not willing or not available for follow-up assessments.
Any condition which in the investigator's opinion makes the patient unsuitable for the study participation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493636

Show 44 Study Locations

Sponsors and Collaborators

Accelerated Community Oncology Research Network

Onyx Pharmaceuticals

Investigators

Study Chair:	Lee S Schwartzberg, MD, FACP	Accelerated Community Oncology Research Network Inc
Study Chair:	Clifford A Hudis, MD	Memorial Sloan-Kettering Cancer Center

More Information

No publications provided

Responsible Party:	Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:	NCT00493636 History of Changes
Other Study ID Numbers:	ACORN AC01B07
Study First Received:	June 26, 2007
Last Updated:	September 28, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Accelerated Community Oncology Research Network:

Breast Cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Capecitabine
Sorafenib
Bevacizumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents

Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 22, 2012