Bevacizumab + Endocrine Treatment vs Endocrine Treatment as First Line Treatment in Postmenopausal Patients With Advanced or Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Hoffmann-La Roche, German Breast Group (GBG).
Information provided by (Responsible Party):
Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier:
NCT00545077
First received: October 16, 2007
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

Locally advanced or metastatic breast cancer in postmenopausal women with negative HER2, who are candidates for hormone treatment and who have not received previous chemotherapy or hormonotherapy for the metastatic disease.

The main endpoint of the study is PFS. It has been calculated that 378 patients will need to be included, according to the following assumptions:

  • Recruitment period of 21 months.
  • Minimum follow-up period of 9 months.
  • PFS of 9 months in the control arm (letrozole in monotherapy). Using a two-sided log-rank test, for a 5% α level, 344 patients (172 in each treatment arm) will be required for 270 events to occur, which will provide an 80% power for detecting a hazard ratio of 0.69 (corresponding to a PFS median of 13 months in the bevacizumab arm). This sample size has been adjusted for an intermediate analysis when 2/3 of the total of required events have occurred. This intermediate analysis can be avoided if, at the time in which it must be carried out, it is estimated that the final analysis will be carried out in 4 months.

Taking into account a 10% percentage of losses, 378 patients are expected to be included in the study.

An intermediate safety evaluation will be carried out when 63 patients have finished their treatment in each treatment arm.


Condition Intervention Phase
Breast Cancer
Drug: Endocrine treatment consisting of either letrozole or fulvestrant.
Drug: Bevacizumab + Endocrine treatment consisting of either letrozole or fulvestrant.
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Randomized Study to Evaluate the Efficacy and Safety of Bevacizumab in Combination With Endocrine Treatment Compared to Endocrine Treatment Alone, in Postmenopausal Women With Advanced or Metastatic Cancer With Indication of Hormonotherapy as First-line Treatment

Resource links provided by NLM:


Further study details as provided by Spanish Breast Cancer Research Group:

Primary Outcome Measures:
  • ·To compare the progression-free survival (PFS) between both treatment arms. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • · Overall survival (OS) · Time to treatment failure (TTF) · Better response to treatment (RR) · Response duration (RD) · Clinical benefit proportion (CBP = CR + PR + SD > 6 months) · Safety and tolerance [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 378
Study Start Date: November 2007
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
• Endocrine treatment consisting of either letrozole or fulvestrant.The patients will be randomized to receive bevacizumab 15mg/kg every 3 weeks plus endocrine treatment or endocrine treatment as a single agent. The patients will receive the assigned treatment until the progression of the disease, unacceptable toxicity or withdrawal of the consent.
Drug: Endocrine treatment consisting of either letrozole or fulvestrant.
The patients will receive the assigned treatment until the progression of the disease, unacceptable toxicity or withdrawal of the consent.
Experimental: B
Bevacizumab: 15 mg/Kg i.v. on day 1 every 3 weeks plus Endocrine treatment consisting of either letrozole or fulvestrant.
Drug: Bevacizumab + Endocrine treatment consisting of either letrozole or fulvestrant.
Bevacizumab will be administered every 21 days (day 1 of cycle 2 will be day 22 of the treatment.The patients will receive the assigned treatment until the progression of the disease, unacceptable toxicity or withdrawal of the consent. Those patients in treatment with bevacizumab who end the study without having progressed will continue to receive the drug out of the study.

Detailed Description:

A multicenter, randomized phase III clinical trial. After verifying the selection criteria, the patients will be randomized to receive letrozole alone or in combination with bevacizumab. Before randomization, the patients will be stratified according to the following prognosis factors:

  • ER+/PgR+ vs the other options (ER+/PgR- vs ER-/PgR+)
  • Previous adjuvant hormonotherapy (yes/no)
  • Status: locally advanced vs metastatic.
  • Measurable vs non measurable disease
  • Visceral disease (yes/no)
  • PFS.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Before starting the specific protocol procedures, the written informed consent must be obtained and documented.
  2. Women ≥ 18 years.
  3. Capacity to comply with all the protocol requirements.
  4. Functional ECOG status of 0 or 1.
  5. Life expectancy ≥ 24 weeks.
  6. Histologically confirmed breast adenocarcinoma, with measurable or non-measurable, locally advanced or metastatic (stage IV) disease. In the event that the patient only has locally advanced disease, she will not be able to undergo curative local treatment. Patients with metastasis confined to the bone can be chosen, but the disease must be confirmed by radiology, CT scan or NMR if there is any doubt after a single bone scan.
  7. Patients with HER2-negative disease evaluated by IHC and FISH/CISH (IHC 0 or 1+, or 2+ and negative FISH). Patients with 3+ by IHC cannot be chosen regardless of the FISH/CISH status and those with positive FISH/CISH (> 2 amplifications) cannot be chosen either, regardless of the IHC findings.
  8. Positive hormone receptors (estrogen receptor [ER] and/or progesterone receptor [PgR]) evaluated by a local or central laboratory, according to the criteria of the participating institution.
  9. Patients who are candidates for receiving first-line treatment with letrozole.
  10. Patients may have received (neo)adjuvant chemotherapy, provided that the last dose of the latter was received at least 12 months before randomization . Patients must be recovered from toxicity.
  11. The patients are allowed to have received adjuvant radiotherapy, provided that it was completed at least 6 weeks before randomization and the patient has recovered from the reversible acute effects of the radiation. The previous administration of radiotherapy to palliate the pain of bone metastases is authorized, provided that:

    • Not more than 30% of bone marrow has been irradiated.
    • The patient has recovered from the reversible acute effects of the radiation.
    • The patient has at least one metastatic location which has not been irradiated and which may be evaluated for progression, or a clear progression of the bone disease has been objectified after the end of the palliative radiotherapy.

Exclusion Criteria:

  1. Evolutionary disease requiring an immediate treatment with cytotoxic chemotherapy according to the investigator's judgment.
  2. Patients with locally advanced breast cancer who are expected to undergo surgery or curative radiotherapy.
  3. Previous chemotherapy or hormonotherapy for the metastatic disease. Patients may have received neoadjuvant chemotherapy or neoadjuvant hormonotherapy with curative intention as a part or as an alternative to an adjuvant treatment. For the previous neoadjuvant hormonotherapy the same premises than for the adjuvant hormonotherapy are valid.
  4. Previous therapy with anti-VEGF or VEGFR tyrosine-kinase inhibitors.
  5. History of another pathology that may affect the development of the protocol or the interpretation of results. It is considered that patients who have suffered from a skin carcinoma that is not melanoma, cervical carcinoma in situ or another neoplasia treated with a curative intention and with a disease-free interval exceeding 5 years can be chosen.
  6. Evidence of CNS metastasis. A CT scan or brain NMR must be done within the 4 weeks before the randomization in case of suspecting brain metastasis.
  7. History or evidence in the physical or neurological examination of CNS pathology unrelated to cancer unless it is suitable treated with standard therapy (e.g. uncontrolled convulsions).
  8. History of peripheral neuropathy NCI CTCAE grade >2 at the time of randomization.
  9. Patients subjected to major surgical procedures, open biopsies or those having significant trauma injuries within the 28 days prior to randomization, or patients who are expected to undergo a major surgical procedure that must necessarily be performed within the course of the study.
  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: NCT00545077

  Show 85 Study Locations
Sponsors and Collaborators
Spanish Breast Cancer Research Group
Hoffmann-La Roche, German Breast Group (GBG).
Investigators
Study Director: Sibylle Loibl, PhD., MD. GBG Forschungs GmbH
Study Director: Miguel Martín, PhD., MD Hospital Clínico San Carlos
Study Director: Juan De la Haba, PhD., MD. Hospital Provincial de Córdoba
  More Information

Additional Information:
No publications provided

Responsible Party: Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT00545077     History of Changes
Other Study ID Numbers: GEICAM/2006-11/GBG 51, Nº EudraCT: 2007-002841-19
Study First Received: October 16, 2007
Last Updated: November 21, 2012
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Letrozole
Fulvestrant
Estradiol
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Estrogens
Hormones

ClinicalTrials.gov processed this record on October 19, 2014