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

Breast Cancer Clinical Trial

Official title:

A Phase II Trial of Oral Deforolimus (AP23573; MK-8669), an mTOR Inhibitor, in Combination With Trastuzumab for Patients With HER2-positive Trastuzumab-Refractory Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00736970
• Other study ID #: 8669-009
• Secondary ID: AP23573-08-207
• Status: Completed
• Phase: Phase 2
• First received: August 14, 2008
• Last updated: August 26, 2015
• Start date: July 2008
• Est. completion date: May 2011

Study information

• Verified date: August 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: May 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• ridaforolimus
10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus.
• trastuzumab
single intravenous infusion every week; initial dose of 4 mg/kg over 90 minutes, then 2 mg/kg over 30 minutes

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) measured by modified RECIST guidelines		Duration of the study	No
Secondary	Characterize the overall safety and tolerability of oral deforolimus administered in combination with standard dose trastuzumab		Duration of the study	Yes
Secondary	Evaluate the clinical-benefit response rate (CR or PR, or SD = six 4-week cycles)		Throughout the trial	No
Secondary	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	No
Secondary	Perform exploratory molecular analyses		Duration of the trial	No