Study to Compare Vinorelbine In Combination With the mTOR Inhibitor Everolimus vs. Vinorelbin Monotherapy for Second-line Treatment in Advanced Breast Cancer (VicTORia)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by AIO-Studien-gGmbH
Sponsor:
Information provided by (Responsible Party):
AIO-Studien-gGmbH
ClinicalTrials.gov Identifier:
NCT01520103
First received: January 25, 2012
Last updated: April 8, 2014
Last verified: June 2012
  Purpose

The purpose of this study is Examination of the superiority of a combination of vinorelbine with the mTOR Inhibitor Everolimus vs. vinorelbine monotherapy for second-line treatment in advanced breast cancer.


Condition Intervention Phase
Her2-negative Metastatic Breast Cancer
Her2-negative Locally Advanced Breast Cancer
Drug: Vinorebine, Everolimus
Drug: Vinorelbine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study to Compare Vinorelbine In Combination With the mTOR Inhibitor Everolimus vs. Vinorelbin Monotherapy for Second-line Treatment in Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by AIO-Studien-gGmbH:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Assessment over 36 months, minimum 12 month ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) will be defined as the time from randomization to the time of disease progression or relapse or death.


Secondary Outcome Measures:
  • Safety and tolerability [ Time Frame: Assessment over 36 months ] [ Designated as safety issue: Yes ]

    Capture all adverse events, serious adverse events, all side effects of the study medication, serious side effects, adverse events that lead to temporary or complete discontinuation of the study treatment and the Rates and causes of death.

    A safety interims analysis is planned, as soon as 60 subjects have finished at least two treatment cycles.


  • Rate of Progression Free Survival after 6 months (6 months PFSR) [ Time Frame: Assessment over 36 months ] [ Designated as safety issue: No ]
    descriptive Evaluation, for the monotherapy (arm 2) a median PFS of 4 months is assumed. It is expected that the combination therapy will prolong the median PFS to 6.5 months.

  • Overall survival (OS) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    The duration of overall survival (OS) will be determined by measuring the time interval from randomization to the date of death or last observation.

  • Response rate (CR, PR) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    The tumour status of patients will be evaluated nine weekly during the treatment until detection of progression.


Estimated Enrollment: 166
Study Start Date: January 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vinorelbin and Everolimus Drug: Vinorebine, Everolimus
Vinorelbin: i.v. 25 mg/ m² d1, d8, d15 3qw Everolimus: oral 5 mg/d d1-21 3qw until progress
standard therapy
Vinorelbin
Drug: Vinorelbine
Vinorelbin: i.v. 25 mg/ m² d1, d8, d15 3qw until progress

  Eligibility

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

Inclusion Criteria:

1 .Dated and signed patient informed consent before start of any in the protocol specified procedures 2. Histologically or cytologically confirmed Her2/neu negative, metastatic or locally advanced breast cancer, including inoperable local relapse, with measurable or non-measurable lesions for which

  • a palliative second line chemotherapy is indicated. Antihormone palliative pretreatments do not count as separate treatment lines
  • treatment with anthracycline and/or taxanes has failed or is not suitable
  • which cannot be adequately treated by operation or radiotherapy on its own 3. An exclusive anti-hormone therapy is not indicated for the patient 4. ECOG Performance Status of 0-2 5. Women >= 18 years of age 6. Life expectancy of at least 12 weeks 7. Adequate bone marrow, liver and renal function (according to SmPC of Vinorelbine, Afinitor®) based on laboratory assessments raised within 7 days prior to start of study treatment:
  • Haemoglobin >= 9.0 g/dl
  • Absolute neutrophil count (ANC) >= 2/mm³
  • Thrombocytes >= 100/µl
  • INR >= 2
  • Serum bilirubin =< 1.5x upper limit of normal ( in patients with known Gilbert syndrome, total bilirubin =< 3x upper limit of normal, with direct bilirubin =< 1.5x upper limit of normal
  • ALT and AST =< 2.5x upper limit of normal (=< 5x upper limit of normal in subjects with liver metastases)
  • Serum cholesterol =< 300 mg/dl or 7.75 mmol/l and triglycerides =< 2.5x upper limit of normal (with lipid lowering drugs permitted)
  • Serum creatinin =< 2x upper limit of normal 8. Documentation of a negative pregnancy test in women of childbearing potential within 7 days prior to start of study. Sexual active pre-menopausal women are required to use adequate contraception throughout the duration of the study, except for oestrogen containing contraceptives

Exclusion Criteria:

  1. Previous treatment with Vinorelbine or an inhibitor of mTOR
  2. Treatment with other study medication within 28 days before start of treatment
  3. Patients who have received prior radiotherapy to ≥ 25% of the bone marrow
  4. Other tumours in the previous 5 years with exception of an adequately treated basal cell carcinoma of the skin or a preinvasive cervix carcinoma
  5. Simultaneous use of known CYP3A4 inducers (e.g. Phenytoin, Rifampicin) or inhibitors of this enzyme (e.g. Itraconazole, Ketoconazole), therefore also use of mistletoe, St John's wort or grapefruit juice
  6. Patients to whom at least one of the conditions applies:

    • Substance abuse
    • medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results as judged by the investigator
    • Legal incapacity or limited legal capacity
    • Subjects who are unable to take oral medication
    • Any condition that could jeopardise the safety of the patient and their compliance in the study as judged by the investigator
  7. History of cardiac dysfunction including one of the following:

    • Myocardial infarction by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function
    • History of documented congestive heart failure (NYHA ≥ 3)
    • Documented cardiomyopathy
  8. Known HIV infection or chronic hepatitis B or C or history of hepatitis B / C
  9. Active clinically relevant infection (> grade 2 NCI-CTC Version 4.03)
  10. Clinical or radiological detection of CNS metastases
  11. Patients receiving concomitant immunosuppressive agents or chronic use of corticosteroids at the time of study entry except in cases outlined below:

    • topical applications (e.g. rash,) inhaled sprays, (e.g. obstructive airway diseases) eye drops or local injections (e.g. intraarticular) are allowed
  12. Active bleeding diathesis or an oral anti-vitamin K medication (except low-dose warfarin and aspirin or equivalent, as long as the INR ≤ 2)
  13. Kidney function disorder requiring dialysis
  14. Seriously impaired liver function (Child-Pugh, class C)
  15. Known hypersensitivity reaction to Vinorelbine or Everolimus
  16. Pregnant or breast-feeding subjects
  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: NCT01520103

Contacts
Contact: Luise Straßl luise.strassl@iomedico.com
Contact: Helge Schröder Helge.Schroeder@aio-studien-ggmbh.de

Locations
Germany
Hämatologisch-onkologische Gemeinschaftspraxis, Münster Recruiting
Münster, Germany, 48149
Contact: Christian Lerchenmüller, Dr.       lerchenmueller@onkologie-muenster.de   
Principal Investigator: Christian Lerchenmüller, Dr.         
Sponsors and Collaborators
AIO-Studien-gGmbH
Investigators
Principal Investigator: Christian Lerchenmüller, Dr. Hämatologisch-onkologische Gemeinschaftspraxis, Münster
  More Information

Additional Information:
No publications provided

Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT01520103     History of Changes
Other Study ID Numbers: AIO-MAM-0110, 2011-001024-38
Study First Received: January 25, 2012
Last Updated: April 8, 2014
Health Authority: Germany: Ethics Commission
Germany: Paul-Ehrlich-Institut

Keywords provided by AIO-Studien-gGmbH:
Metastatic breast cancer
locally advanced breast cancer
Her2/new negative
HER2 negative

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Everolimus
Sirolimus
Vinorelbine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 18, 2014