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

NCT00736970 | Completed Phase 2

• 2 other identifiers: 8669-009AP23573-08-207
• Study Type: interventional
• Target: 34
• Locations: 0 countries
• Sites: N/A

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

Keywords

ridaforolimus; deforolimus; AP23573; breast cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) measured by modified RECIST guidelines

  Duration of the study

Secondary Outcomes (4)

• Characterize the overall safety and tolerability of oral deforolimus administered in combination with standard dose trastuzumab

  Duration of the study

• Evaluate the clinical-benefit response rate (CR or PR, or SD ≥ six 4-week cycles)

  Throughout the trial

• Evaluate additional efficacy endpoints, such as duration of response, time to tumor progression, progression-free survival, progression free survival rate, and overall survival

  Duration of the trial

• Perform exploratory molecular analyses

  Duration of the trial

Study Arms (1)

1

EXPERIMENTAL

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

Drug: ridaforolimus; Drug: trastuzumab

Interventions

ridaforolimus DRUG

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

Also known as: deforolimus, AP23573, MK-8669, ridaforolimus was also known as deforolimus until May 2009

1

trastuzumab DRUG

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

Also known as: Herceptin

1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 25239224 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ridaforolimus; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2008
• First Posted: August 18, 2008
• Study Start: July 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: May 1, 2011
• Last Updated: August 27, 2015

Record last verified: 2015-08