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

This study has been completed.
Sponsor:
Collaborator:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:
NCT00493636
First received: June 26, 2007
Last updated: May 15, 2014
Last verified: May 2014
  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:


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 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, assessed up to 39 months. ] [ 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, assessed up to 56 months. ] [ 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), assessed up to 39 months. ] [ 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, assessed up to 39 months. ] [ Designated as safety issue: No ]
    Overall response rate was defined as the proportion of participants experiencing complete response (CR) and partial response (PR) as best overall response. Response was evaluated via changes from baseline in radiological tumor measurements using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.

  • 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 ]
    Duration of overall response was calculated as the time (days) from first documentation of CR or PR (whichever status is recorded first) until the first date that recurrent or progressive disease (PD) or death is objectively documented. Response was evaluated via changes from baseline in radiological tumor measurements using RECIST version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.


Enrollment: 160
Study Start Date: June 2007
Study Completion Date: November 2012
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A (Sorafenib + Gemcitabine or Capecitabine)
Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours); Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle; 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)
Drug: Gemcitabine
Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle
Other Name: Gemzar
Drug: Sorafenib
Sorafenib will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)
Other Name: Nexavar
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).
Other Name: Xeloda
Placebo Comparator: B (Placebo + Gemcitabine or Capecitabine)
Placebo will be administered ( 2 tablets ) orally twice daily (approximately every 12 hours); Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle; 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)
Drug: Gemcitabine
Gemcitabine will be administered 1000 mg/m2 pm Days 1 and 8 of a 21 day cycle
Other Name: Gemzar
Drug: Placebo
Placebo will be administered (400 mg; 2 tablets x 200 mg) orally twice daily (approximately every 12 hours)
Other Name: Sugar pill
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).
Other Name: Xeloda

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 by Accelerated Community Oncology Research Network

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Results First Received: April 17, 2014
Last Updated: May 15, 2014
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
Bevacizumab
Gemcitabine
Capecitabine
Sorafenib
Fluorouracil
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014