A phase IIb study of ridaforolimus, dalotuzumab and exemestane in combination in advanced breast cancer

• Register: EUCTR
• Last refreshed on: 23 July 2018
• Main ID: EUCTR2012-000335-11-ES
• Date of registration: 26/04/2012
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: A phase IIb study of ridaforolimus, dalotuzumab and exemestane in combination in advanced breast cancer
• Scientific title: A Phase 2 Randomized Trial of the Combination of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in High Proliferation, Estrogen Receptor Positive Breast Cancer Patients - A phase IIb study of ridaforolimus, dalotuzumab and exemestane in combination in adv breast cancer
• Date of first enrolment: 21/06/2012
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000335-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: yes; Other specify the comparator: Ridaforolimus-Exemestane; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Brazil, Canada, Colombia, Czech Republic, Denmark, Germany, Israel, Italy, Korea, Democratic People's Republic of, Peru, Portugal, Spain, Sweden, Taiwan, United States

Contacts

• Name: Marta Arias-Salgado
• Affiliation: Merck, Sharp & Dohme de España, S.A.

• Name: Marta Arias-Salgado
• Affiliation: Merck, Sharp & Dohme de España, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Metastatic, ER positive, HER2 negative Breast Cancer
2. High Proliferative (as measured by a Ki67 labeling index >15%)
3. Post menopausal
4. Previous treatment with either letrozole or anastrozole
5. AT least 1 measurable lesion
6. At least 18 years of age
7. Greater than or equal to 1 on the ECOG performance status.
8. Life expectance greater than 3 months
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion criteria:
1. Patient is on other therapy for their cancer (Bisphosphonates and denosumab for the treatment of bone metastases are allowed, if they were initiated at least 28 days prior to randomization.)
2. Patient is in another study or is receiving an experimental agent.
3. Patient has previously received rapamycin or rapamycin analogs, including ridaforolimus, temsirolimus, or everolimus.
4. Patient has received prior treatment with IGF-1R inhibitors, PI3K inhibitors, or other experimental agents that target PI3K, AKT, or mTOR pathway
5. Patient who has had chemotherapy, radiotherapy, or biological therapy within 4 weeks [(6 weeks for nitrosoureas, mitomycin C, or bevacizumab and 2 weeks for hormonal therapy and kinase inhibitors)] prior to entering the study or who has not recovered from adverse events from prior treatment to at least grade 1 or baseline.
6. Patient has active brain metastasis or leptomeningeal carcinomatosis;
7. Patient has poorly controlled Type 1 or 2 diabetes, defined as a hemoglobin A1C greater than 8% or a fasting glucose of > 160 mg/dL.
8. Patient is known to be HIV positive.
9. Patient has a known history of active Hepatitis B or C. Patients who are seropositive for Hepatitis B surface antibody as their only evidence of prior hepatitis exposure are allowed.
10. Patient has a requirement for concurrent treatment with medications that are inducers or inhibitors of cytochrome P450 (CYP3A). Patients should be off these medications for at least 2 weeks prior to the first dose of ridaforolimus. Concomitant medications that are metabolized by CYP3A are allowed (e.g., simvastatin or atorvastatin). See Appendix 6.1 for examples of CYP3A inducers and inhibitors.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

ER positive, high proliferation breast
MedDRA version: 14.1 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: ridaforolimus
Product Code: MK-8669
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: ridaforolimus
CAS Number: 572924-54-0
Current Sponsor code: MK-8669
Other descriptive name: RIDAFOROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: dalotuzumab
Product Code: MK-0646
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: dalotuzumab
CAS Number: 1005389-60-5
Current Sponsor code: MK-0646
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Exemestane 25mg Film-coated Tablets.
Exemestano 25 mg comprimidos recubiertos con película
Product Name: Exemestano
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EXEMESTANO
CAS Number: 107868-30-4
Other descriptive name: Aromasin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): 1.Progression Free Survival according to RECIST 1.1.

Main Objective: The primary objective of the study is to evaluate the progression free survival (PFS) for the triplet combination of ridaforolimus, dalotuzumab and exemestane (R/D/E) compared to the combination of ridaforolimus and exemestane (R/E) in post-menopausal patients with high proliferation, estrogen receptor positive breast cancer that have progressed following treatment with a non-steroidal aromatase inhibitor.

Secondary Objective: ? In post-menopausal patients with high proliferation, estrogen receptor positive breast cancer who have progressed following treatment with a non-steroidal aromatase inhibitor, the secondary objectives of this trial are the following:
?To evaluate the effectiveness of the triplet combination of ridaforolimus, exemestane and dalotuzumab (R/D/E) compared to ridaforolimus and exemestane (R/E) with respect to percent (%) reduction from baseline in the sum of imaging measurements (target lesion line lengths or volumetric images) at 16 weeks.
?To evaluate the objective response rate, as measured by RECIST 1.1 of the triplet combination of R/D/E compared to the combination of R/E.
?To estimate the overall survival for the triplet combination of R/D/E compared to the combination of R/E.

Timepoint(s) of evaluation of this end point: Every 8 calendar weeks while on treatment

Secondary Outcome(s)

Secondary end point(s): 1. Percent (%) change from baseline in the sum of target lesions by linear CT analysis at 16 weeks.
2. Percent (%) change from baseline in the sum of target lesions by tumor volume analysis at 16 weeks
3. Objective response rate, as measured by RECIST 1.1.
4. Overall survival will be assessed every 3 months

Timepoint(s) of evaluation of this end point: :16 weeks for endpoints 1 and 2. Every 8 weeks for objective 3 every three months after disease progression.

Secondary ID(s)

8669-064

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.