Study Evaluating Temsirolimus (CCI-779) In Breast Neoplasms

April 13, 2011 updated by: Wyeth is now a wholly owned subsidiary of Pfizer

A Phase 2 Randomized Open-Label Study Of Letrozole In Combination With Two Dose Levels And Schedules Of Oral Temsirolimus (CCI-779), Or Letrozole Alone, In Postmenopausal Women With Locally Advanced Or Metastatic Breast Cancer

To evaluate the preliminary activity and pharmacokinetics of 2 separate doses and schedules of orally administered Temsirolimus (CCI-779) given in combination with daily letrozole, compared to letrozole alone, in the treatment of locally advanced or metastatic breast cancer in postmenopausal women. All patients must be appropriate to receive endocrine therapy as treatment for advanced disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

108

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Postmenopausal women with histologically confirmed, measurable locally advanced disease or metastatic breast.
  • Must be appropriate to receive endocrine therapy as treatment for advanced disease (chemotherapy; prior adjuvant therapy with antiestrogens other than aromatase inhibitors; prior adjuvant or first-line metastatic therapy with tamoxifen or trastuzumab, are permitted).
  • Women may either present with de novo advanced or metastatic cancer, or have had tumor progression while receiving adjuvant tamoxifen or at any time after completing adjuvant tamoxifen, or have had tumor progression while receiving first-line metastatic therapy with tamoxifen.

Exclusion Criteria:

  • Patients having known central nervous system (CNS) metastases.
  • Prior therapy with Temsirolimus (CCI-779) or aromatase inhibitors.
  • Tamoxifen, or other hormonal therapy, in the metastatic or adjuvant setting within 1 week prior to day 1 of treatment on study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Drug: Letrozole / Temsirolimus (CCI-779)
Letrozole 2.5 mg daily + Temsirolimus (CCI-779) 10 mg daily
Drug: Letrozole / Temsirolimus (CCI-779)
Letrozole 2.5 mg daily + Temsirolimus (CCI-779) intermittent 30 mg daily for five days every 2 weeks
Other Names:
  • Letrozole / Temsirolimus(CCI-779), Torisel
Experimental: B
Drug: Letrozole / Temsirolimus (CCI-779)
Letrozole 2.5 mg daily + Temsirolimus (CCI-779) 10 mg daily
Drug: Letrozole / Temsirolimus (CCI-779)
Letrozole 2.5 mg daily + Temsirolimus (CCI-779) intermittent 30 mg daily for five days every 2 weeks
Other Names:
  • Letrozole / Temsirolimus(CCI-779), Torisel
Active Comparator: C
Drug: Letrozole
Letrozole 2.5 mg daily
Other Names:
  • Letrozole alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Objective Response (OR)
Time Frame: Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression
OR measured as Complete response (CR) or Partial response (PR) confirmed by assessments performed no less than 4 weeks after the criteria for the response are first met. CR=disappearance of all target and non-target lesions with normalization of tumor marker level; PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, referencing the screening sum LD. Target lesions=all measurable lesions up to 5 lesions per organ (10 lesions in total), representative of all involved organs, if possible; recorded and measured at screening. Non-target lesions=all other lesions.
Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Best Overall Response (Clinical Benefit)
Time Frame: Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression)
Best response (CR, PR, or stable disease (SD) lasting ≥6 months) recorded from baseline to disease progression or recurrence (Progressive disease [PD]). CR=disappearance of all target and non-target lesions with normalization of tumor marker level; PR is ≥30% decrease in sum of LD of target lesions; SD=neither sufficient shrinkage to=PR nor sufficient increase to=PD, referencing smallest sum LD since treatment started; PD is ≥20% increase in sum of LD of target lesions referencing smallest sum of LD; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions.
Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression)
Time to Disease Progression
Time Frame: Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression)
Number of days to disease progression defined as the interval from the date of randomization until the first date that recurrence or progression is documented; progression (at least 20% increase in the sum of the LD of target lesions taking as reference the smallest sum of LD; appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions).
Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression)
Time to Treatment Failure
Time Frame: Baseline until Progressive disease, death, or discontinuation of study treatment
Number of days to treatment failure defined as interval from start of treatment to first date of progressive disease (at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD since the treatment started; appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions) or death or discontinuation of treatment due to Adverse Event, censored at last evaluation.
Baseline until Progressive disease, death, or discontinuation of study treatment
Percentage of Participants Exhibiting Freedom From Progression
Time Frame: Baseline, 8 weeks, 6 months, 12 months, and 24 months
Freedom from progression defined as CR (disappearance of all target and non-target lesions with normalization of tumor marker level), PR (at least a 30% decrease in sum of the LD of target lesions taking as reference the screening sum LD), or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD [at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD since the treatment started; appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions]).
Baseline, 8 weeks, 6 months, 12 months, and 24 months
Duration of Response
Time Frame: Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression)
Duration of response is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that reoccurrence or PD is objectively documented, taking as reference for PD the smallest measurements recorded since the treatment started. SD is measured from the start of the treatment until the criteria for disease progression are met, taking as reference the smallest measurements recorded since the treatment started; the minimal time interval for duration of SD is 8 weeks.
Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression)
Number of Participants With Survival
Time Frame: Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) until death
Number of participants with survival (alive) in the interval from start of treatment to last contact for participant or death as a result of any cause.
Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) until death
Health Outcomes Assessment: EuroQol (EQ-5D) Health State Profile Score
Time Frame: Prior to baseline, Cycle 7 (Week 12) and final visit (within 15 days of stopping study treatment)
EQ-5D is a self-administered questionnaire to assess health-related quality of life in 5 domains (mobility, self care, usual activities, pain or discomfort, and anxiety or depression). Scores from the 5 domains are used to calculate the Health State Profile Score as a single index value; range: 0.0 (death) to 1.0 (perfect health); higher scores indicate a better health state.
Prior to baseline, Cycle 7 (Week 12) and final visit (within 15 days of stopping study treatment)
Health Outcomes Assessment: European Organization for Research and Treatment of Cancer Quality of Life Questionaire (EORTC QLQ) BR23
Time Frame: Prior to baseline, Cycle 7 (Week 12) and final visit (within 15 days of stopping study treatment)
Assess specificity of breast cancer symptoms relevant to participant's perceived quality of life (disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm or shoulder pain, breast pain, swollen breast, and skin problems on the breast). 23-item assessment of symptoms or problems during the past week (items 1-13 and 17-23) or during the past 4 weeks (items 14-16); range from 1 (not at all) to 4 (very much). Index scores transformed and range from 0 to 100; higher scores indicate higher level of functioning and quality of life.
Prior to baseline, Cycle 7 (Week 12) and final visit (within 15 days of stopping study treatment)
Number of Participants With Antitumor Response in Relation to Expression of Akt Phosphorylation, Cyclin D1, PTEN, and p27
Time Frame: Prior to baseline, after Cycle 4 (Week 8), after Cycle 8 (Week 14), and cross-over or final visit (within 15 days of stopping study treatment)
Number of participants with antitumor response (CR [disappearance of all target and non-target lesions with normalization of tumor marker level] or PR [at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, referencing the screening sum LD]) in relation to plasma levels of Akt phosphorylation, cyclin D1, PTEN, and p27.
Prior to baseline, after Cycle 4 (Week 8), after Cycle 8 (Week 14), and cross-over or final visit (within 15 days of stopping study treatment)
Area Under the Concentration-time Curve (AUC) Sum
Time Frame: Cycle 1 Day 1 (1 cycle is defined as a 14 day duration) , Cycle 3 Day 1, and Cycle 4 Day 1, Day 6, Day 9, Day 11, and Day 12
Area under the concentration-time curve to infinity (AUC) measured as hours multiplied by nanograms divided by milliliters (hr*ng/mL) for CCI-779, sirolimus and letrozole. Sum is calculated as the sum of CCI-779 plus sirolimus AUCs (AUCsum).
Cycle 1 Day 1 (1 cycle is defined as a 14 day duration) , Cycle 3 Day 1, and Cycle 4 Day 1, Day 6, Day 9, Day 11, and Day 12
24-hour Trough Concentration (C Trough)
Time Frame: Cycle 1 Day 1 (1 cycle is defined as a 14 day duration) , Cycle 3 Day 1, and Cycle 4 Day 1, Day 6, Day 9, Day 11, and Day 12
C trough in whole blood measured as nanograms per milliliter (ng/mL).
Cycle 1 Day 1 (1 cycle is defined as a 14 day duration) , Cycle 3 Day 1, and Cycle 4 Day 1, Day 6, Day 9, Day 11, and Day 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wyeth is now a wholly owned subsidiary of Pfizer

Collaborators

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2002

Primary Completion (Actual)

April 1, 2005

Study Completion (Actual)

October 1, 2009

Study Registration Dates

First Submitted

June 12, 2003

First Submitted That Met QC Criteria

June 12, 2003

First Posted (Estimate)

June 13, 2003

Study Record Updates

Last Update Posted (Estimate)

April 15, 2011

Last Update Submitted That Met QC Criteria

April 13, 2011

Last Verified

April 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3066A1-204
  • B1771005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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