CCI-779 in Treating Patients With Extensive-Stage Small Cell Lung Cancer
CCI-779 in Treating Patients With Extensive-Stage Small Cell Lung Cancer
Randomized phase II trial to compare the effectiveness of different doses of CCI-779 in
 treating patients who have extensive-stage small cell lung cancer. Drugs used in chemotherapy
 use different ways to stop tumor cells from dividing so they stop growing or die
PRIMARY OBJECTIVES:

 I. To study the progression-free survival in patients who receive a lower or a higher dose of
 CCI-779, a cytostatic agent following cytoreductive chemotherapy in extensive SCLC.

 II. To determine the toxicity of two treatment regimens involving a lower or a higher dose of
 CCI-779.

 SECONDARY OBJECTIVES:

 I. To quantify the effects of CCI-779 treatment on p70S6 phosphorylation in peripheral blood
 mononuclear cells of patients with small cell lung cancer who are treated with CCI-779.

 II. To measure the effects on mTOR activation and signaling of plasma from patients treated
 with CCI-779.

 III. To determine the relationship between CCI-779 dose and its pharmacodynamic parameters.

 IV. To correlate the inhibition of p70S6 with indices of patient outcome.

 OUTLINE: This is a randomized, multicenter study. Patients are stratified according to brain
 metastases (yes vs no), prior induction chemotherapy regimen (platinum and etoposide vs
 platinum and irinotecan), and response to prior induction chemotherapy (complete or partial
 response vs stable disease). Patients are randomized to 1 of 2 treatment arms.

 ARM I: Patients receive low-dose CCI-779 IV over 30 minutes once weekly. Treatment continues
 in the absence of disease progression or unacceptable toxicity.

 ARM II: Patients receive high-dose CCI-779 as in arm I.

 Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
 annually thereafter.
Inclusion Criteria:

 -  Patients must have histologically-confirmed small cell carcinoma of the lung or
 unequivocally positive cytological evidence (sputum [at least 2] or aspirate biopsy),
 with extensive disease (disease beyond the hemithorax and adjacent nodes,
 supraclavicular node involvement or pleural effusion with positive cytology), who have
 required induction chemotherapy, who have responding or stable disease, and who meet
 the following criteria:

 -  Induction chemotherapy including platinum (cisplatin or carboplatin) plus either
 etoposide (VP-16) or irinotecan (CPT-11)

 -  A minimum of 3 and a maximum of 6 cycles of induction chemotherapy have been
 administered

 -  Recovered from all toxicity related to prior chemotherapy (except alopecia and/or
 neuropathy)

 -  No less than 4 and no more than 8 weeks have elapsed between the last treatment
 of induction chemotherapy and randomization

 -  No more than 32 weeks have elapsed between the first dose of induction
 chemotherapy and date of randomization

 -  The patient has responding or stable disease using RECIST criteria since the
 initiation of systemic chemotherapy (i.e., patients who have exhibited disease
 progression are NOT ELIGIBLE)

 -  Patients must be disease-free for >= 5 years if they have had a prior second
 malignancy other than treated basal cell or squamous cell skin cancer, or carcinoma in
 situ of the cervix

 -  Baseline measurements/evaluations of disease must be obtained =< 4 weeks prior to
 randomization

 -  WBC >= 4000/mm³ or

 -  ANC >= 1500/mm³

 -  Platelet count >= 100,000/mm³

 -  Total bilirubin =< 1.5 mg/dl

 -  Creatinine =< 1.5 mg/dl

 -  Patient's cholesterol level must be < 350mg/dl; (note; if non-fasting levels are high
 repeat in a fasting state)

 -  Patient's triglycerides must be < 400mg/dl; (note; if non-fasting levels are high
 repeat in a fasting state)

 -  ECOG performance status 0, 1, or 2

 -  Prior radiation to any symptomatic site is permitted so long as the site(s) of
 measurable disease are NOT irradiated, and radiation is completed at least 4 weeks
 before randomization

 -  Patients must not have had prior treatment with biological response modifiers

 -  Patients with brain metastases are eligible provided they have received treatment, are
 asymptomatic and are no longer taking corticosteroids; patients who develop brain
 metastases after completion of induction chemotherapy are ineligible

 -  Patients must not be on anticonvulsant therapy

 -  Patients must not have limited disease

 -  Patients must not become pregnant and must practice adequate contraception; women of
 child-bearing potential and men must agree to use adequate contraception (hormonal or
 barrier method of birth control) prior to study entry, for the duration of study
 participation and continue approximately 12 weeks after the study is completed; should
 a woman become pregnant or suspect she is pregnant while participating in this study,
 she should inform her treating physician immediately; female patients who are
 breastfeeding are also excluded from this study

 -  Patients must not have history of allergic reactions attributed to compounds of
 similar chemical or biologic composition to CCI-779, or to any of the components of
 the CCI-779 formulation; patients must also not be allergic to or for medical reasons
 are unable to receive antihistamines

 -  Patients must not be immunocompromised, have an active infection or serious
 intercurrent infection, or have received known immunosuppressive therapies within 3
 weeks randomization