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Completed

NCT Number: NCT01231659

Safety and Efficacy of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

This was a multi-center, Israeli phase II open label study evaluating treatment with RAD001 (10 mg daily) combined with letrozole (2.5 mg daily) in postmenopausal women after recurrence or progression on Tamoxifen, Anastrozole or Examestane.

There were no treatments specifically approved after recurrence or progression on AIs. Available options, based on common clinical practice and several treatment guidelines (e.g. NCCN treatment guidelines 2008), included fulvestrant.

Combining RAD001 with letrazole was a rational approach to the treatment of advanced Brest Cancer, offering the potential for inhibition of tumor cell growth\\ proliferation and anti angiogenesis while at the same time potentially preventing the development of letrazole resistance.

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Key information

Conditions

Postmenopausal Women Breast Diseases Breast Neoplasms Locally Advanced Metastatic Breast Cancer Metastatic Breast Cancer Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Jerusalem, Israel

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About this study

Screening Period:

Postmenopausal women with estrogen receptor positive, locally advanced or metastatic breast cancer whose disease was refractory to hormonal therapy and had a documented recurrence or progression on last therapy for their breast cancer with either tamoxifen, anastrozole, letrozole, fulvestrant or exemestan were screened for eligibility within 28 days prior to treatment Day 1.

Treatment Period:

Patients started receiving everolimus (10 mg daily oral dose) combined with letrozole (2.5 mg daily oral dose) tablets from treatment Day 1. Study treatment continued until disease progression, intolerable toxicity or consent withdrawal. Dose adjustment (reduction, interruption or possible dose re-escalation to starting dose) could be done based on the safety findings. Tumor assessments were performed every 12 weeks until disease progression. In order to confirm response at least four weeks after first observation, additional scans to determine a complete response (CR) or partial response (PR) or stable disease (SD) were performed. Patients were followed for safety until 28 days after study treatment discontinuation.

Post Treatment Follow up for Survival:

Patients were followed for survival every 3 months for up to 3 years. Survival information could be obtained via phone and information was documented in the source documents.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer after documented recurrence or progression on Tamoxifen, Anastrozole or Examestane.
  • Refractory disease to hormonal therapy is defined as:
  • Recurrence while on, or within 12 month of end of, adjuvant treatment with Tamoxifen , Anastrozole, or Exemestane.
  • Recurrence while on, or within 24 month of end of, adjuvant treatment with Letrozole.
  • Progression while on Tamoxifen, Anastrozole or Exemestane treatment for locally advanced or metastatic breast cancer.

Exclusion criteria

  • Prior use of chemotherapy and letrozole for Advanced Breast Cancer and mTOR inhibitors as the last anticancer treatment prior to study entry.
  • Patients must have radiological evidence of recurrence or progression on last therapy prior to study entry.

Treatment and study plan

Everolimus

Drug

Everolimus 10 mg (2 tablets of 5 mg) once daily

Other names: RAD001

letrozole

Drug

Letrozole 2.5 mg once daily

Primary outcomes

  1. Percentage of Participants With Overall Response Rate (ORR)

    Time frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 15 months

    Overall Response Rate (ORR) was defined as the proportion of patients whose best overall response was either complete response (CR) or partial response (PR) according to RECIST 1.0 for target lesions and assessed by CT: Complete Response (CR), disappearance of all target lesions for a period of at least one month; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (ORR) = CR + PR. Only descriptive statistics.

Secondary outcomes

  1. Median Time to Progression-Free Survival (PFS)

    Time frame: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 66 months

    Progression Free Survival (PFS) was defined as the time from the date of study entry to the date of first documented tumor progression or death from any cause, whichever occurred first. If a patient did not have an event, PFS was censored at the last date of tumor assessment. For patients with measurable disease at baseline, progression was determined according to the RECIST 1.0 criteria. Only descriptive analysis done.

  2. Median Time to Overall Survival (OS)

    Time frame: From Date of randomization up to approximately 66 months

    Overall Survival (OS) was defined as the time from the date of study entry to date of death due to any cause. If a death had not observed by the date of analysis, then OS was censored at the date of last contact. Distribution of OS was estimated using the Kaplan Meier method. The median OS along with 95% CI was presented.

  3. Disease Control Rate (DCR)

    Time frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 66 months

    Disease Control Rate (DCR) was defined as the proportion of patients whose best overall response was either: Complete Response (CR), Partial Response (PR) or Stable Disease (SD). Disease Control Rate was calculated only for patients with measurable disease at baseline and was summarized using descriptive statistics.

  4. Long-term Safety and Tolerability

    Time frame: From Date of first dose up to approximately 66 months

    The assessment of safety was based mainly on the frequency of AEs and on the number of laboratory values that fell outside of pre-determined ranges. Other safety data (e.g. ECG, vital signs) were considered as appropriate. Only descriptive analysis done.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

Phase II Open Label Study of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic, Estrogen Receptor Positive Breast Cancer, After Failure of Tamoxifen and/or Anastrozole and/or Letrozole and/or Fulvestrant and/or Exemestane

Important dates

Study start
2011
Primary completion
2012
Study completion
2017
First posted
Nov 1, 2010
Registry last updated
Mar 26, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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