Study Evaluating Temsirolimus (CCI-779) In Breast Neoplasms

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT00062751
First received: June 12, 2003
Last updated: April 13, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Breast Neoplasms
Drug: Letrozole / Temsirolimus (CCI-779)
Drug: Letrozole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Wyeth is now a wholly owned subsidiary of Pfizer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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).

  • Time to Treatment Failure [ Time Frame: Baseline until Progressive disease, death, or discontinuation of study treatment ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Exhibiting Freedom From Progression [ Time Frame: Baseline, 8 weeks, 6 months, 12 months, and 24 months ] [ Designated as safety issue: No ]
    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]).

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Survival [ Time Frame: Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) until death ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    C trough in whole blood measured as nanograms per milliliter (ng/mL).


Enrollment: 108
Study Start Date: December 2002
Study Completion Date: October 2009
Primary Completion Date: April 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Letrozole / Temsirolimus (CCI-779)
Letrozole 2.5 mg daily + Temsirolimus (CCI-779) 10 mg daily
Experimental: B Drug: Letrozole / Temsirolimus (CCI-779)
Letrozole 2.5 mg daily + Temsirolimus (CCI-779) intermittent 30 mg daily for five days every 2 weeks
Other Name: Letrozole / Temsirolimus(CCI-779), Torisel
Active Comparator: C Drug: Letrozole
Letrozole 2.5 mg daily
Other Name: Letrozole alone

  Eligibility

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

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.
  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: NCT00062751

Sponsors and Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc
ClinicalTrials.gov Identifier: NCT00062751     History of Changes
Obsolete Identifiers: NCT00061971
Other Study ID Numbers: 3066A1-204, B1771005
Study First Received: June 12, 2003
Results First Received: October 27, 2010
Last Updated: April 13, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Wyeth is now a wholly owned subsidiary of Pfizer:
breast
neoplasms

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Sirolimus
Everolimus
Letrozole
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014