Clinical trial NCT00781846: Trial of Deforolimus in Combination With Bevacizumab for Patients With Advanced Cancers (8669-010)(COMPLETED)
Official title: A Phase I Trial of Oral Deforolimus (AP23573; MK-8669), an mTOR Inhibitor, in Combination With Bevacizumab for Patients With Advanced Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Ariad Pharmaceuticals
First posted: 2008-10-29
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety, tolerability, and recommended phase 2 dose of oral ridaforolimus administered in combination with intravenous bevacizumab in patients with advanced cancers.


Eligibility criteria: Inclusion Criteria:

* 18 years of age or older
* Advanced or metastatic solid tumor malignancy
* ECOG performance status of less than or equal to 1
* Life expectancy of greater than 3 months
* At least 4 weeks must have elapsed between prior investigational therapy, chemotherapy, or radiotherapy, and the first dose of deforolimus
* 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
* Signed informed consent
* Women of childbearing potential must have a negative serum pregnancy test within 7 days of starting therapy and must use an approved contraceptive method from time of screening until 30 days after the last dose of study drug

Exclusion Criteria:

* Tumor location in close proximity to a major blood vessel
* History of brain metastases, spinal cord compression, or carcinomatous meningitis. Primary brain tumors (for example, glioblastoma) are allowed.
* New brain metastases, spinal cord compression, or leptomeningeal metastases on screening CT scan or MRI
* Hemoptysis or hematemesis within 28 days prior to entering the trial
* Clinical significant unexplained bleeding within 28 days prior to entering the trial
* Uncontrolled hypertension
* Proteinuria at screening
* Clinically significant cardiovascular disease
* Newly diagnosed or poorly controlled type 1 or 2 diabetes
* Active infection requiring prescribed intervention
* Other concurrent illness that, in the Investigator's judgement, would either compromise the patient's safety or interfere with the evaluation of the safety of the study drug
* Major surgery within 28 days before trial entry, or any incompletely healed surgical incision; minor surgery or procedures within 7 days
* Pregnant or breastfeeding
* Known allergy to macrolide antibiotics
* Known hypersensitivity to any component of bevacizumab
* Concurrent treatment with medications that strongly induce or inhibit cytochrome P450 (CYP3A)
* Known history of HIV sero-positivity
* Any condition in the Investigator's judgement that renders the patient unable to fully understand and provide informed consent and/or comply with the protocol

Primary outcomes:
measure: Identification of recommended phase 2 dose of ridaforolimus in combination with bevacizumab
timeFrame: Duration of the trial
Secondary outcomes:
measure: Characterize the overall safety and tolerability of ridaforolimus in combination with bevacizumab
timeFrame: Duration of the study
measure: Description of the anti-tumor activity of ridaforolimus in combination with bevacizumab
timeFrame: Duration of the study
Other outcomes:
Locations:
Study officials:
affiliation: Ariad Pharmaceuticals
name: Frank Haluska, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Nemunaitis J, Hochster HS, Lustgarten S, Rhodes R, Ebbinghaus S, Turner CD, Dodion PF, Mita MM. A phase I trial of oral ridaforolimus (AP23573; MK-8669) in combination with bevacizumab for patients with advanced cancers. Clin Oncol (R Coll Radiol). 2013 Jun;25(6):336-42. doi: 10.1016/j.clon.2013.02.005. Epub 2013 Apr 21.