Oral Deforolimus With Trastuzumab for Patients With HER2-positive Trastuzumab-Refractory Metastatic Breast Cancer (8669-009)

NCT ID: NCT00736970

Last Updated: 2015-08-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2011-05-31

Brief Summary

This clinical trial will study the use of ridaforolimus in metastatic breast cancer subjects whose tumors have shown a resistance to trastuzumab (herceptin). The goal of this study is to find out if subjects treated with ridaforolimus in combination with trastuzumab have a positive response to the treatment, and if treatment with ridaforolimus in combination with trastuzumab prolongs survival.

Conditions

Breast Cancer; Breast Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus

Group Type: EXPERIMENTAL

ridaforolimus

Intervention Type: DRUG

10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus.

trastuzumab

Intervention Type: DRUG

single intravenous infusion every week; initial dose of 4 mg/kg over 90 minutes, then 2 mg/kg over 30 minutes

Interventions

ridaforolimus

10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus.

Intervention Type: DRUG

trastuzumab

single intravenous infusion every week; initial dose of 4 mg/kg over 90 minutes, then 2 mg/kg over 30 minutes

Intervention Type: DRUG

Other Intervention Names

deforolimus; AP23573; MK-8669; ridaforolimus was also known as deforolimus until May 2009; Herceptin

Eligibility Criteria

Inclusion Criteria

• Female, 18 years of age or older
• Histologically confirmed HER2-positive metastatic breast cancer
• Trastuzumab-resistance
• Measurable disease, according to RECIST guidelines
• ECOG performance status less than or equal to 1
• Life expectancy greater than 3 months
• No prior treatment with temsirolimus, everolimus, rapamycin, or any other mTOR inhibitor
• At least 4 weeks must have lapsed between prior investigational therapy, chemotherapy or radiotherapy, and the first dose of ridaforolimus
• Left ventricular ejection greater than or equal to 50%
• Adequate cardiovascular function
• Adequate hematological, hepatic, and renal function
• Serum cholesterol less than or equal to 350 mg/dL and triglycerides less than or equal to 400 mg/dL
• Negative pregnancy test within 7 days prior to first dose of study drug and must use an approved contraceptive method from screening to 30 days after the last dose of study drug
• Availability and patient consent to obtain archival tissue samples
• Signed informed consent

Exclusion Criteria

• Inadequate recovery from any prior surgical procedure or having undergone any major surgery within 2 weeks before trial entry
• Grade 1 or Grade 2 hypersensitivity reactions to prior trastuzumab therapy if these reactions prevented further trastuzumab administration
• Grade 3 or Grade 4 hypersensitivity reaction to prior trastuzumab
• Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
• Known allergy to macrolide antibiotics
• Pregnant or breast-feeding
• Know history of HIV
• Diagnosis of brain metastasis or leptomeningeal carcinomatosis within 3 months
• Other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin
• Active infection requiring prescription intervention
• Newly diagnosed or poorly controlled Type 1 or 2 diabetes
• Other concurrent illness which, in the Investigator's judgment, would either compromise the patient's safety or interfere with the evaluation of the safety of the study drug
• Concurrent treatment with medications that strongly induce or inhibit cytochrome P450.
• Any condition that renders patient unable to fully understand and provide informed consent and/or comply with the protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Seiler M, Ray-Coquard I, Melichar B, Yardley DA, Wang RX, Dodion PF, Lee MA. Oral ridaforolimus plus trastuzumab for patients with HER2+ trastuzumab-refractory metastatic breast cancer. Clin Breast Cancer. 2015 Feb;15(1):60-5. doi: 10.1016/j.clbc.2014.07.008. Epub 2014 Aug 17.

Reference Type: RESULT

PMID: 25239224 (View on PubMed)

Other Identifiers

AP23573-08-207

Identifier Type: OTHER

Identifier Source: secondary_id

8669-009

Identifier Type: -

Identifier Source: org_study_id