A Study of Avastin (Bevacizumab) in Combination With Chemotherapy in Patients With Breast Cancer Progressing After First-Line Therapy With Avastin and Chemotherapy (TANIA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01250379
First received: November 25, 2010
Last updated: June 5, 2015
Last verified: June 2015

November 25, 2010
June 5, 2015
February 2011
December 2013   (final data collection date for primary outcome measure)
  • Percentage of Participants With Second-Line Progressive Disease (PD) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) or Death (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (less than or equal to [≤] 28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    Second-line progression-free survival (PFS) was defined as the time from randomization to PD or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For target lesions (TLs), PD was defined at least a 20 percent (%) increase in the sum of the largest diameter (SLD), taking as reference the smallest SLD recorded from baseline (BL) or the appearance of one or more new lesions. For non-target lesions (NTLs), PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
  • Second-Line PFS (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    The median time, in months, from randomization to second-line PFS event. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
  • Probable Percentage of Participants Estimated to be Alive and Free of Disease Progression at 6, 12, 18, and 24 Months (Data Cutoff 20 December 2013) [ Time Frame: Months 6, 12, 18, and 24 ] [ Designated as safety issue: No ]
    Second-line PFS was defined as the time from randomization to PD or death due to any cause during their second-line of treatment with bevacizumab and/or chemotherapy, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from BL or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
Second-line progression-free survival (PFS), tumour assessments according to RECIST criteria by Computed Tomography (CT)/Magnetic Resonance Imaging (MRI)/bone scans and X-ray [ Time Frame: approximately 42 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01250379 on ClinicalTrials.gov Archive Site
  • Second-Line PFS by Baseline Risk Factor (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    The median time, in months, from randomization to second-line PFS event according to the following baseline risk factors: hormone receptor negative, HER2 negative (triple negative), hormone receptor positive/HER-2 negative (HR-pos/HER-neg), first-line PFS less than (<) 6 months, first-line PFS greater than or equal to (≥) 6 months, taxane chemotherapy (chemo), non-taxane chemo, vinorelbine chemo, LDH ≤ 1.5 upper limit of normal (ULN), LDH greater than (>) 1.5 ULN, < 65 years of age, ≥ 65 years of age, < 70 years of age, ≥ 70 years of age, < 3 metastatic organ sites, ≥ 3 metastatic organ sites, bevacizumab-free (B-free) interval ≤ 6 weeks, B-free > 6 weeks, disease-free (D-free) interval ≤ 24 months, D-free > 24 months, D-free ≤ 12 months, and D-free > 12 months. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology.
  • Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    BOR was defined as a confirmed CR or PR during second-line treatment. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. The 95% Cl was determined using the Pearson-Clopper method.
  • Percentage of Participants With a CR, PR, Stable Disease (SD), and PD According to RECIST v1.1 (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. The 95% CI was determined using the Pearson-Clopper method.
  • Duration of Objective Response (DOR) (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    The median time, in months, from the date of the first second-line documentation of CR or PR according to RECIST v1.1 to the date of the first second-line documentation of PD or death due to any cause. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels, and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants with CR or PR who had experienced neither disease progression nor died were censored at the date of the last available tumor assessment when the participant was known to be progression free.
  • Probable Percentage of Participants With a Documented PR or CR According to RECIST v1.1 Estimated to be Alive and Free of Disease Progression at 3, 6, and 9 Months (Data Cutoff 20 December 2013) [ Time Frame: Months 3, 6, and 9 ] [ Designated as safety issue: No ]
    DOR was defined as the median time, in months, from the date of the first second-line documentation of CR or PR to the date of the first second-line documentation of PD or death due to any cause. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels, and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants with CR or PR who had experienced neither disease progression nor died were censored at the date of the last available tumor assessment when the participant was known to be progression free.
  • Percentage of Participants With Third-Line PD According to RECIST v1.1 or Death (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    Third-line PFS was defined as the time from the date of first dose of third-line bevacizumab and/or chemotherapy to the date of third-line PD or death due to any cause. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from BL or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented. Participants without third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
  • Third-Line PFS (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    The median time, in months, from the first dose of third-line bevacizumab and/or chemotherapy to third-line PFS event. Participants without third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
  • Percentage of Participants With Second- and Third-Line PD According to RECIST v1.1 or Death (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    Second- and third-line PFS was defined as the time from the date randomization to the date of third-line PD or death due to any cause. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from BL or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
  • Second- and Third-Line PFS (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    The median time, in months, from randomization to third-line PFS event. Participants without third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
  • Percentage of Participants With Second- and Third-Line Tumor Progression (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    Second- and third-line tumor progression was defined as the time from the date of randomization to the date of third-line PD according to RECIST v1.1 or death due to progression of disease. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from BL or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without third-line PD or death due to progression of disease were censored at the date of last tumor assessment where non-progression was documented.
  • Time to Second- and Third-Line Tumor Progression (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter according to the standard of care of the treatment site until PD, or end of efficacy follow-up, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    The median time, in months, from randomization to second- and third-line PFS event. Participants without third-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
  • Percentage of Participants Who Died (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL, every 3-4 weeks thereafter according chemotherapy regimen until end of treatment or third-line PD, weekly thereafter until death or end of study up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
  • Overall Survival (OS) (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL, every 3-4 weeks thereafter according chemotherapy regimen until end of treatment or third-line PD, weekly thereafter until death or end of study up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Participants who had not died were censored at the date the patient was last known to be alive.
  • Probable Percentage of Participants Estimated to be Surviving at 6, 12, 18, and 24 Months (Data Cutoff 20 December 2013) [ Time Frame: Months 6, 12, 18, and 24 ] [ Designated as safety issue: No ]
    OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Participants who had not died were censored at the date the patient was last known to be alive.
  • Percentage of Participants Experiencing Problems by European Quality of Life Instrument (EQ-5D) Category (Data Cutoff 20 December 2013) [ Time Frame: BL, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD. ] [ Designated as safety issue: No ]
    The EQ-5D is composed of 5 single-item measures where participants responded to questions assessing health status by responding with either "no problems", "some problems", or "extreme problems" in the following categories: mobility (M) ("no problems"="I have no problems in walking about" to "extreme problems"="I am confined to bed"), self-care (SC) ("no problems"="I have no problems with self-care" to "extreme problems"="I am unable to wash or dress myself"), usual activities (UA) ("no problems"="I have no problems performing my usual activities" to "extreme problems"="I am unable to perform my usual activities"), pain/discomfort (P/D) ("no problems"="I have no pain or discomfort" to "extreme problems"="I have extreme pain or discomfort"), and anxiety/depression (A/D) ("no problems"="I am not anxious or depressed" to "extreme problems"='I am extremely anxious or depressed").
  • Quality of Life Assessed As an Index Score Using the EQ-5D (Data Cutoff 20 December 2013) [ Time Frame: BL, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD. ] [ Designated as safety issue: No ]
    The EQ-5D is composed of 5 single-item measures where participants responded to questions assessing health status by responding with either "no problems", "some problems", or "extreme problems" in the following categories: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Based on large population surveys, an algorithm was used to combine the responses to each of these 5 measures into 1 single EQ-5D index score ranging from -0.59 (extreme problems) to +1 (no problems).
  • Change From BL in EQ-5D Index Scores (Data Cutoff 20 December 2013) [ Time Frame: BL, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD. ] [ Designated as safety issue: No ]
    The EQ-5D is composed of 5 single-item measures where participants responded to questions assessing health status by responding with either "no problems", "some problems", or "extreme problems" in the following categories: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Based on large population surveys, an algorithm was used to combine the responses to each of these 5 measures into 1 single EQ-5D index score ranging from -0.59 (extreme problems) to +1 (no problems) where a negative value indicated a worsening of perceived quality of life and a positive value indicated an improvement of perceived quality of life.
  • Quality of Life Assessed Using the EQ-5D Visual Analogue Scale (VAS) Scores (Data Cutoff 20 December 2013) [ Time Frame: BL, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD. ] [ Designated as safety issue: No ]
    The participant was asked to rate their overall health on a 0-100 millimeter (mm) vertical scale, where the lowest endpoint=0 (labeled as worst imaginable health state) and the highest endpoint =100 (labeled as the best imaginable health state). The participant marked the line corresponding to their assessment and the distance from the bottom was measured in millimeters. A higher value indicated a better health state.
  • Change From BL in VAS Scores (Data Cutoff 20 December 2013) [ Time Frame: BL, during second-line treatment at Weeks 8 and 16 (4-week cycles) or Weeks 9 and 18 (3-week cycles) and at second-line PD. ] [ Designated as safety issue: No ]
    The participant was asked to rate their overall health on a 0-100 mm vertical scale, where the lowest endpoint=0 (labeled as worst imaginable health state) and the highest endpoint =100 (labeled as the best imaginable health state). The participant marked the line corresponding to their assessment and the distance from the bottom was measured in millimeters. A negative value indicated a worsening of perceived quality of life and a positive value indicated an improvement of perceived quality of life
  • Functional Assessment of Cancer Therapy-Breast (FACT-B) Scores (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter until second-line PD, or end of efficacy followup, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    The Functional Assessment of Cancer Therapy-Breast (FACT-B) is composed of 5 multi-item sections where participants responded to questions assessing symptoms (scale: 0-4; 0="not at all" and 4="very much"), as follows: physical well-being (PWB) (7 items, total score 0-28), social/family well-being (SWB) (7 items, total score 0-28), emotional well-being (EWB) (6 items, total score 0-24), functional well-being (FWB) (7 items, total score 0-28); and breast cancer score based on the additional concerns section of FACT-B (10 items, total score 0-40). The FACT-B Trial Outcomes Index (TOI) score=sum of PWB, FWB, and breast cancer score subscale scores (total score 0-96). The Functional Assessment of Cancer Therapy-General (FACT-G) total score=sum of PWB, SWB, EWB, and FWB subscales scores (total score 0-108). The FACT-B total score=sum of PWB, SWB, EWB, FWB, and breast cancer score subscales scores (total score 0-148). In all cases a higher value indicated a better perceived quality of life.
  • Change From BL in FACT-B Scores (Data Cutoff 20 December 2013) [ Time Frame: Screening, BL (≤28 days after randomization), every 8-9 weeks thereafter until second-line PD, or end of efficacy followup, up to data cutoff of 20 December 2013 (up to 35 months). ] [ Designated as safety issue: No ]
    The FACT-B is composed of 5 multi-item sections where participants responded to questions assessing symptoms (scale: 0-4; 0="not at all" and 4="very much"), as follows: PWB (7 items, total score 0-28), SWB (7 items, total score 0-28), EWB (6 items, total score 0-24), FWB (7 items, total score 0-28); and breast cancer score based on the additional concerns section of FACT-B (10 items, total score 0-40). The FACT-B TOI score=sum of PWB, FWB, and breast cancer score subscale scores (total score 0-96). The FACT-G total score=sum of PWB, SWB, EWB, and FWB subscales scores (total score 0-108). The FACT-B total score=sum of PWB, SWB, EWB, FWB, and breast cancer score subscale scores (total score 0-148). In all cases a higher value indicated a better perceived quality of life.
  • Third-line PFS, tumour assessments according to RECIST criteria by CT/MRI/bone scan and X-ray [ Time Frame: approximately 42 months ] [ Designated as safety issue: No ]
  • Second-line Overall Response Rate (ORR), tumour assessments according to RECIST criteria by CT/MRI/bone scan and x-ray [ Time Frame: approximately 42 months ] [ Designated as safety issue: No ]
  • One-year survival [ Time Frame: approximately 42 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: approximately 42 months ] [ Designated as safety issue: No ]
  • Quality of life: Functional assessment of cancer therapy - breast (FACT-B) scale, EuroQuol (EQ-5D) questionnaire [ Time Frame: approximately 42 months ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 42 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of Avastin (Bevacizumab) in Combination With Chemotherapy in Patients With Breast Cancer Progressing After First-Line Therapy With Avastin and Chemotherapy (TANIA)
A Phase III Randomized Study Evaluating the Efficacy and Safety of Continued and Re-induced Bevacizumab in Combination With Chemotherapy for Patients With Locally Recurrent or Metastatic Breast Cancer After First-line Chemotherapy and Bevacizumab Treatment

This randomized, open-label, parallel-group study will assess the efficacy and s afety of Avastin (bevacizumab) in combination with chemotherapy versus chemother apy alone as second- and third-line therapy in patients with locally recurrent o r metastatic breast cancer progressing after first-line therapy with Avastin and chemotherapy. Patients will be randomized to receive either Avastin (15 mg/kg e very 3 weeks or 10 mg/kg every 2 weeks intravenously) plus standard chemotherapy or chemotherapy alone. Anticipated time on study treatment is until third-line disease progression or unacceptable toxicity occurs.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • Drug: bevacizumab [Avastin]
    10 mg/ kg iv every 2 weeks or 15 mg/kg iv every 3 weeks
  • Drug: Chemotherapy
    Standard chemotherapy (doublets not allowed)
  • Active Comparator: 1
    Intervention: Drug: Chemotherapy
  • Experimental: 2
    Interventions:
    • Drug: bevacizumab [Avastin]
    • Drug: Chemotherapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
494
March 2015
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Female patients, >/= 18 years of age
  • Histologically confirmed HER2-negative breast cancer
  • Disease progression during or following first-line treatment with Avastin and chemotherapy for locally recurrent or metastatic breast cancer
  • Avastin treatment in first-line setting must have been a minimum of 4 cycles (15 mg/kg) or 6 cycles (10 mg/kg) in combination with chemotherapy
  • ECOG performance status 0-2
  • At least 28 days since prior radiation therapy or surgery and recovery from treatment

Exclusion Criteria:

  • Anti-angiogenic therapy or anti-vascular endothelial growth factors other than Avastin for first-line treatment
  • Active malignancy other than superficial basal cell and superficial squamous cell carcinoma of the skin, or in situ carcinoma of the cervix or breast within the last 5 years
  • Inadequate renal function
  • Clinically relevant cardio-vascular disease
  • Known CNS disease except for treated brain metastases
  • Chronic daily treatment with high-dose aspirin (>325 mg/day) or clopidogrel (>75 mg/day)
  • Pregnant or lactating women
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Austria,   Brazil,   Croatia,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Slovakia,   Spain,   Switzerland
 
NCT01250379
MO22998, 2010-020998-16
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
June 2015

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