AzTrials
AzTrials

Breast NeoplasmsPhase 2NCT01605396

A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)

A Phase 2 study testing Ridaforolimus, Dalotuzumab and Exemestane in people with Breast Neoplasms, run by Merck Sharp & Dohme LLC.

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

The purpose of the study is to evaluate the efficacy of the triplet of ridaforolimus, dalotuzumab and exemestane compared to the combination of ridaforolimus and exemestane in post-menopausal participants with breast cancer. 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?
Ridaforolimus, Dalotuzumab and Exemestane
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
No sites listed yet
Study dates
4 Jul 2012to 15 Mar 2018
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

  • Females with a histologically confirmed diagnosis of breast cancer that is metastatic or locally advanced (locally advanced tumors must not be amenable to
  • surgery or radiation therapy with curative intent) with the following pathological characteristics determined locally: estrogen receptor positive and Human Epidermal Growth Factor Receptor 2 (HER-2) negative, and Ki67 (a tumor marker) ≥ 15% determined by the central study laboratory
  • Post-menopausal
  • With advanced breast cancer whose disease was refractory to previous letrozole or anastrozole
  • Has at least one confirmed measurable metastatic lesion
  • Has a performance status ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Has a life expectancy of at least 3 months
  • Adequate organ function

Who cannot join

  • Is receiving any other concurrent systemic tumor therapy, including
  • hormonal agents and HER-2 inhibitors
  • Previously received rapamycin or rapamycin analogs, including
  • ridaforolimus, temsirolimus, or everolimus
  • Received prior treatment with Insulin-like Growth Factor 1 Receptor (IGF-1R) inhibitors, Phosphatidylinositol 3-Kinase (PI3K) inhibitors, or
  • other experimental agents that target PI3K, Protein Kinase B (AKT), or Mammalian Target of Rapamycin (mTOR) pathway
Show all 16Show fewer
  • Is receiving chronic corticosteroids administered at doses greater than
  • those used for normal replacement therapy
  • Has active brain metastasis or leptomeningeal carcinomatosis; patients
  • with adequately treated brain metastases are eligible if they meet certain criteria
  • Known allergy to macrolide antibiotics
  • Has an active infection requiring antibiotics
  • Significant or uncontrolled cardiovascular disease
  • Poorly controlled Type 1 or 2 diabetes
  • Is known to be Human Immunodeficiency Virus (HIV) positive
  • Has a known history of active hepatitis B or C. Healthy carriers of hepatitis B are not allowed on this study

About this study

Official title: A Phase II Randomized Trial of the Combination of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in High Proliferation, Estrogen Receptor Positive Breast Cancer Patients

The purpose of the study is to evaluate the efficacy of the triplet of ridaforolimus, dalotuzumab and exemestane compared to the combination of ridaforolimus and exemestane in post-menopausal participants with breast cancer. The primary hypothesis of the study is that the triplet of ridaforolimus, dalotuzumab and exemestane will improve progression free survival (PFS) compared to ridaforolimus and exemestane.

Being tested
Ridaforolimus, Dalotuzumab, Exemestane
Medical subject headings
Breast Neoplasms

What participants receive

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

  • RidaforolimusDrug

    Also called MK-8669, AP23573

    Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, \& 22-26 of 28-day cycle.

  • DalotuzumabDrug

    Also called MK-0646, h7C10

    Dalotuzumab administered 10 mg/kg IV weekly on Days 1, 8, 15, and 22 of 28-day cycle.

  • ExemestaneDrug

    Also called Aromasin

    Exemestane 25 mg tablet administered PO QD.

Study groups in NCT01605396
Study groupRoleWhat they receive
Ridaforolimus + Dalotuzumab + ExemestaneExperimentalParticipants receive ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.
Receives: Drug: Ridaforolimus; Drug: Dalotuzumab; Drug: Exemestane
Ridaforolimus + ExemestaneActive comparatorParticipants receive ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
Receives: Drug: Ridaforolimus; Drug: Exemestane

What is being measured

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

  1. 1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)

    PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first. Response was assessed according to RECIST 1.1 by BICR. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval [CI]) in weeks was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression. All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.

    Measured: From Day 1 through last post-study efficacy follow-up (up to ~19 months)

Secondary outcomes (3)

  1. Percent Change From Baseline in Sum of Target Lesion Diameters at Week 16

    The percent change from baseline to Week 16 in the sum of target lesion diameters as determined by anatomic imaging was defined as the line length (i.e., diameter) for each target lesion identified at baseline summed across all lesions at baseline, and separately at each post-baseline time point. The primary analysis was conducted using a constrained longitudinal data analysis (cLDA) method and target lesion measurements according to the BICR. Percent change from baseline in sum of target lesion diameters at Week 16 was reported for each treatment arm.

    Measured: Baseline, Week 16

  2. 3. Percentage of Participants With Objective Response (Objective Response Rate [ORR]) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR).

    ORR was defined as the percentage of participants whose best response was complete response (CR; disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or partial response (PR; at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression.

    Measured: From Day 1 through last post-study efficacy follow-up (up to ~19 months)

  3. Overall Survival (OS)

    OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date last known to be alive. OS was analyzed using the Kaplan-Meier method and median OS (95% confidence interval [CI]) in weeks was reported for each treatment arm. Per protocol, all participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.

    Measured: From Day 1 through last post-study efficacy follow-up (up to ~19 months)

Timeline

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

  1. First posted24 May 2012 (estimated)
  2. Study start4 Jul 2012
  3. Primary completion19 Feb 2014
  4. Study completion15 Mar 2018

Resources

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
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01605396
Sponsor's protocol ID
8669-064
Other IDs
2012-000335-11, MK-8669-064
Status last verified
Mar 2019
First submitted
22 May 2012
Last updated
25 Mar 2019
Data monitoring committee
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Rugo HS, Tredan O, Ro J, Morales SM, Campone M, Musolino A, Afonso N, Ferreira M, Park KH, Cortes J, Tan AR, Blum JL, Eaton L, Gause CK, Wang Z, Im E, Mauro DJ, Jones MB, Denker A, Baselga J. A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer. Breast Cancer Res Treat. 2017 Oct;165(3):601-609. doi: 10.1007/s10549-017-4375-5. Epub 2017 Jul 5.

    PubMed 28681171

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ridaforolimus, Dalotuzumab and Exemestane in people with Breast Neoplasms, run by Merck Sharp & Dohme LLC.

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 8 inclusion and 16 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 25 Mar 2019. 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 Mar 2019). 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?

1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) (time frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)). 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 NCT01605396, which also lists 1 linked publication.

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 25 Mar 2019.

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