Breast NeoplasmsPhase 2NCT00062751

Study Evaluating Temsirolimus (CCI-779) In Breast Neoplasms

A Phase 2 study testing Letrozole / Temsirolimus (CCI-779) and Letrozole in people with Breast Neoplasms, run by Wyeth is now a wholly owned subsidiary of Pfizer.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Neoplasms
What is being tested?: Letrozole / Temsirolimus (CCI-779) and Letrozole
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 108 participants
Where: No sites listed yet
Study dates: Dec 2002to Oct 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

About this study

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

Conditions: Breast Neoplasms
Being tested: Letrozole / Temsirolimus (CCI-779), Letrozole
Keywords: breast, neoplasms
Medical subject headings: Breast Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Letrozole / Temsirolimus (CCI-779)Drug
Letrozole 2.5 mg daily + Temsirolimus (CCI-779) 10 mg daily
Letrozole / Temsirolimus (CCI-779)Drug
Also called Letrozole / Temsirolimus(CCI-779), Torisel
Letrozole 2.5 mg daily + Temsirolimus (CCI-779) intermittent 30 mg daily for five days every 2 weeks
LetrozoleDrug
Also called Letrozole alone
Letrozole 2.5 mg daily

Study groups in NCT00062751
Study group	Role	What they receive
A	Experimental	Not described Receives: Drug: Letrozole / Temsirolimus (CCI-779)
B	Experimental	Not described Receives: Drug: Letrozole / Temsirolimus (CCI-779)
C	Active comparator	Not described Receives: Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants With Objective Response (OR)
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.
Measured: 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 outcomes (11)

Percentage of Participants With Best Overall Response (Clinical Benefit)
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.
Measured: 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
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).
Measured: 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
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.
Measured: Baseline until Progressive disease, death, or discontinuation of study treatment
Percentage of Participants Exhibiting Freedom From Progression
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]).
Measured: Baseline, 8 weeks, 6 months, 12 months, and 24 months
Duration of Response
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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).
Measured: 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)
C trough in whole blood measured as nanograms per milliliter (ng/mL).
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2002Oct 2009

First posted13 Jun 2003 (estimated)
Study startDec 2002
Primary completionApr 2005
Study completionOct 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 108 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00062751
Sponsor's protocol ID: 3066A1-204
Other IDs: B1771005
Status last verified: Apr 2011
First submitted: 12 Jun 2003
Last updated: 15 Apr 2011
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 15 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00062751
Acronym / sponsor ID: 3066A1-204
Conditions: Breast Neoplasms
Keywords: breast, neoplasms
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 108 participants (actual)
Lead sponsor: Wyeth is now a wholly owned subsidiary of PfizerIndustry (pharma, biotech, devices)
Collaborators: Pfizer
Study start: Dec 2002
Primary completion: Apr 2005 (actual)
Study completion: Oct 2009 (actual)
First posted: 13 Jun 2003 (estimated)
Results: Posted 25 Nov 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
A	Experimental	Drug: Letrozole / Temsirolimus (CCI-779)
B	Experimental	Drug: Letrozole / Temsirolimus (CCI-779)
C	Active comparator	Drug: Letrozole

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Letrozole / Temsirolimus (CCI-779)Letrozole 2.5 mg daily + Temsirolimus (CCI-779) 10 mg daily	Drug	A
Letrozole / Temsirolimus (CCI-779)Also: Letrozole / Temsirolimus(CCI-779), ToriselLetrozole 2.5 mg daily + Temsirolimus (CCI-779) intermittent 30 mg daily for five days every 2 weeks	Drug	B
LetrozoleAlso: Letrozole aloneLetrozole 2.5 mg daily	Drug	C

Primary outcome

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.

11 secondary outcomes

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)
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)
Time to Treatment Failure
Time frame: 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
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)
Number of Participants With Survival
Time frame: 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)
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)
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)
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
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

Results and safety

Results posted to the registry on 25 Nov 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Let 2.5 mg Plus 10 mg Daily CCI-779	33	0
Let 2.5 mg Plus 30 mg Intermittent CCI-779	30	0
Let 2.5 mg Alone / Cross-over to 75 mg Intermittent CCI-779	33	3
Let 2.5 mg Plus 25mg Daily CCI-779	6	1
Let 2.5 mg Plus 75 mg Intermittent CCI-779	6	0

Primary outcome: 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. Number (95% Confidence Interval). Unit: percentage of participants

Population analysed: Intent to treat population (ITT) defined as all participants randomized in the study. Final efficacy analysis was not conducted because the development of temsirolimus (CCI-779) for the treatment of breast cancer was terminated.

11 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Let 2.5 mg Plus 10 mg Daily CCI-779	12 of 33 (36.4%)	33 of 33 (100%)	Not reported
Let 2.5 mg Plus 30 mg Intermittent CCI-779	10 of 30 (33.3%)	30 of 30 (100%)	Not reported
Let 2.5 mg Alone Prior to Cross-over to 75 mg Intermit CCI-779	9 of 33 (27.3%)	32 of 33 (97%)	Not reported
After Cross-over to 75 mg Intermittent CCI-779	1 of 18 (5.6%)	16 of 18 (88.9%)	Not reported
Let 2.5 mg Plus 25mg Daily CCI-779	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
Let 2.5 mg Plus 75 mg Intermittent CCI-779	1 of 6 (16.7%)	6 of 6 (100%)	Not reported

Limitations and caveats (from the sponsor): Clinical development of oral temsirolimus for treatment of locally advanced or metastatic breast cancer was terminated by Wyeth based on the results of a phase 3 clinical study with the combination temsirolimus and letrozole.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Letrozole / Temsirolimus (CCI-779) and Letrozole in people with Breast Neoplasms, run by Wyeth is now a wholly owned subsidiary of Pfizer.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Nov 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00062751.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2011.