Clinical trial NCT01212627: Ridaforolimus With Cetuximab: Adv Non-Small Cell Lung, Colorectal, Head & Neck Cancer
Official title: BrUOG- Phase 1-233: A Phase I Study of Ridaforolimus With Cetuximab for Patients With Advanced Head and Neck Cancer, Non-Small Cell Lung Cancer and Colon Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
Lead sponsor: Brown University
Sponsor class: OTHER
Collaborators: name: Rhode Island Hospital
name: The Miriam Hospital
name: Memorial Hospital of Rhode Island
name: Roger Williams Medical Center
First posted: 2010-09-30
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the best dose, safety and side effects of ridaforolimus when given with cetuximab for patients with head and neck, lung and colon cancer that has progressed after initial therapy. A second purpose of this study is to gain preliminary information on whether the combination of ridaforolimus and cetuximab is helpful in treating patients with advanced head and neck cancer

Detailed description: Patients with advanced NSCLC, colorectal cancer, and head and neck cancer that progressed after at least 1 prior regimen for metastatic disease were eligible. Wild-type K-ras was required in colon cancer. All patients received cetuximab 400 mg/m2 week 1 followed by 250 mg/m2/week. Four dose levels of ridaforolimus were planned: 10mg, 20mg, 30mg, and 40mg daily, 5 days each week, on a 28-day cycle.

Eligibility criteria: Inclusion Criteria

* Histologically or cytologically advanced head and neck cancer, NSCLC or colorectal cancer (wild-type KRAS) in whom there is no curable option and have progressed after at least one regimen for advanced disease. Once the final dose level has been determined, only patients with advanced lung cancer who fail at least one line of chemotherapy will be eligible to be accrued to the 13 patient expanded cohort. \*\*\* As of July 7, 2011 the final dosing level has been determined and the next cohort of patients with advanced lung cancer will be enrolled\*\*
* Patient has measurable disease by protocol-specific RECIST criteria.
* A minimum of 4 weeks has elapsed between prior chemotherapy and day 1 of study treatment.
* A minimum of 14 days has elapsed since prior kinase inhibitor therapy or radiotherapy, and a minimum of 4 weeks has elapsed since prior bevacizumab.
* No prior exposure to an mTOR inhibitor. Prior cetuximab exposure is allowed.
* ECOG performance status 0-1
* Required initial lab values: Hemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1,500/mm3, platelet count ≥100,000/mm3, total bilirubin ≤1.5 times the upper limit of normal, AST or ALT \<3 times the upper limit of normal, serum albumin ≥2.5 g/dL, serum cholesterol ≤350 mg/dL, triglycerides ≤400 mg/dL, creatinine \<1.5 times the upper limit of normal, or a calculated creatinine clearance ≥50 ml/min.
* Age ≥18 years
* Those of child-bearing potential must agree to use of effective method of contraception
* Patients must have the ability to understand and give written informed consent

Exclusion criteria:

* Patient is known to have active brain metastases. Patients with previously treated brain metastases that are stable for \>3months are eligible if a current brain MRI (within 28 days of day 1 of study treatment) shows no edema or evidence of progression compared to a prior study at least 3 months ago.
* Patient is currently participating or has participated in a study with an investigational anticancer treatment or device within 30 days or 5 half lives of the investigational compound (whichever is greater) of initial dosing with study drug.
* Patient has previously received rapamycin or rapamycin analogs, including ridaforolimus, everolimus, or temsirolimus.
* Patient is receiving corticosteroids administered at doses greater than those used for normal replacement therapy.
* Patient has a history of prior invasive malignancy except for basal cell carcinoma of the skin within the past two years or who is deemed at low risk for recurrence by his treating physician.
* Patient has known severe hypersensitivity to macrolide antibiotics (ie: clarithromycin, erythromycin, or azythromycin).
* Patient has NYHA Class III or IV congestive heart failure or any other significant history of cardiac disease including: myocardial infarction within the last 6 months; ventricular arrhythmia or acute congestive heart failure within the last 3 months; uncontrolled angina or uncontrolled hypertension.
* Patient is known to be HIV positive or has a known history of Hepatitis B or C.
* Patient has a psychiatric disorder that would interfere with cooperation with the requirements of the trial, is a regular user of illicit drugs (including "recreational use"), or has a recent history (within the last year) of drug or alcohol dependence.
* Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study.
* Patient has an active infection requiring intravenous antibiotics.
* Patient has a requirement for concurrent treatment with medications that are strong inducers or inhibitors of cytochrome P450 (CYP3A) (see Appendix). Patients should discontinue 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)

Primary outcomes:
measure: Determine Maximum Tolerated Dose (MTD) of Ridaforolimus With Given With Cetuximab
timeFrame: 1 year
Secondary outcomes:
measure: Check the Tolerability, and Maximum Tolerated Dose (MTD) of Several Dosing Schedules of Oral Ridaforolimus.
timeFrame: 1 year
Other outcomes:
Locations:
city: Pawtucket
country: United States
facility: memorial Hospital of Rhode island
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
Study officials:
affiliation: Lifespan
name: Angela Plette, MD
role: PRINCIPAL_INVESTIGATOR
References: