Phase I/II Study of Paclitaxel / Carboplatin / RAD001 as First Line Therapy for Advanced Adenocarcinoma of the Stomach
- Histologically or cytologically proven adenocarcinoma of the stomach. Patients who
have adenocarcinoma of the gastroesophageal junction will be eligible if the majority
of the tumor bulk is below the junction.
- Metastatic or Loco-regionally advanced disease
- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral CT /MRI scan. See
section 11.2 for the evaluation of measurable disease.
- Age >= 18 years.
- Life expectancy of greater than 12 weeks.
- ECOG performance status <= 2 (Karnofsky >= 60%).
- Patients who have received more than one line of palliative chemotherapy are allowed,
provided that (i) the prior chemotherapy does not contain taxane, cisplatin or
carboplatin; (ii) 4 weeks have elapsed prior to the start of the current study
treatment, and that (iii) they have recovered from adverse events due to previous
treatment [except alopecia].
- Patients who have had radiotherapy or major surgery within 4 weeks prior to entering
the study or those who have not recovered from adverse events due to treatment
administered more than 4 weeks earlier.
- Patients who are on CYP3A4 modifiers are excluded from the study
- Patients with known brain metastases.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to RAD001.
Significant cardiovascular disease including unstable angina pectoris, uncontrolled
hypertension, congestive heart failure related to primary cardiac disease, a condition
requiring anti-arrhythmic therapy, ischemic or severe valvular heart disease, or a
myocardial infarction within 6 months prior to the trial entry.
- Patients with severe concurrent medical illness such as severe impairment of lung
function should be excluded from studies of RAD001.
- Uncontrolled intercurrent such as, but not limited to, ongoing or active infection,
or psychiatric illness/social situations that would limit compliance with study
- Poorly controlled diabetes mellitus
- High LDL cholesterol or triglyceride level
- Pre-existing neuropathy of >= grade 2
- Patients with a history of second malignancies are eligible they have been disease
free for at least 5 years and are deemed by the investigator to be at low risk of
recurrence. Par8entswith the following cancers are eligible if diagnosed and treated
within the past 5 years: cervical carcinoma in situ, melanoma in situ, and basal cell
or squamous cell carcinoma of the skin
- Pregnancy or lactation.