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

This study is ongoing, but not recruiting participants.
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: November 1, 2012
Last verified: November 2012

June 26, 2007
November 1, 2012
June 2007
June 2013   (final data collection date for primary outcome measure)
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 ]
Progression free survival
Complete list of historical versions of study NCT00493636 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Overall Survival
  • Time to progression
  • Overall response rate
  • Duration of overall response
  • Treatment-emergent AEs, laboratory parameters, and vital signs
Not Provided
Not Provided
 
1st or 2nd Line MBC (Metastatic Breast Cancer) With Previous Avastin (Bevacizumab) Therapy
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Breast Cancer
  • 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)
  • 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).
  • 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)
    Interventions:
    • Drug: Gemcitabine
    • Drug: Sorafenib
  • 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)
    Interventions:
    • Drug: Gemcitabine
    • Drug: Placebo
  • 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)
    Interventions:
    • Drug: Sorafenib
    • Drug: 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).
    Interventions:
    • Drug: Placebo
    • Drug: Capecitabine
Schwartzberg LS, Tauer KW, Hermann RC, Makari-Judson G, Isaacs C, Beck JT, Kaklamani V, Stepanski EJ, Rugo HS, Wang W, Bell-McGuinn K, Kirshner JJ, Eisenberg P, Emanuelson R, Keaton M, Levine E, Medgyesy DC, Qamar R, Starr A, Ro SK, Lokker NA, Hudis CA. Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab. Clin Cancer Res. 2013 May 15;19(10):2745-54. doi: 10.1158/1078-0432.CCR-12-3177. Epub 2013 Feb 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
160
June 2013
June 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00493636
ACORN AC01B07
Yes
Accelerated Community Oncology Research Network
Accelerated Community Oncology Research Network
Onyx Pharmaceuticals
Study Chair: Lee S Schwartzberg, MD, FACP Accelerated Community Oncology Research Network Inc
Study Chair: Clifford A Hudis, MD Memorial Sloan-Kettering Cancer Center
Accelerated Community Oncology Research Network
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP