RAD001 With Paclitaxel and Carboplatin in First Line Treatment of Patients With Advanced Large Cell Lung Cancer With Neuroendocrine Differentiation

Study Overview
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Brief Summary
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This is a multi-centric, open-label study evaluating the efficacy and safety of RAD001 in patients with advanced (stage IV) Lung Cancer (Large Cell) with neuroendocrine differentiation treated with a combination of RAD001 with paclitaxel and carboplatin.

Official Title
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A Multi-centric, Open-label, Phase II Study Investigating the Combination of Afinitor With Paclitaxel and Carboplatin in First Line Treatment of Patients With Advanced (Stage IV) Large Cell Lung Cancer With Neuroendocrine Differentiation (LC-NEC)

Conditions
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Carcinoma, Large Cell, Neuroendocrine Tumors

Intervention / Treatment
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* Drug: RAD001
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who give a written informed consent obtained according to local guidelines Histologically confirmed diagnosis of stage IV lung cancer of LC-NEC type according to WHO classification: Histolocial analysis of newly diagnosed disease must not be older than 8 weeks from signed consent Relapse must be confirmed by histology Neuroendocrine differentiation World Health organisation (WHO) performance status grade ≤ 1 measurable disease Adequate bone marrow function Adequate liver function Adequate renal function Exclusion Criteria: History or clinical evidence of central nervous system (CNS) metastases. Presence of SCLC cells Patients who have a history of another primary malignancy ≤ 3 years, with the exception of inactive basal or squamous cell carcinoma of the skin or cervical cancer in situ, early stages of breast cancer (LCIS and DCIS) and prostate cancer (stage T1a) prior chemotherapy for the treatment of advanced lung cancer and/or not having recovered from the side effects of any other therapy (adjuvant treatment for earlier stages I-III is allowed if finished at least one year before study entry) Patients who have received any investigational drug ≤ 28 days before starting study treatment or who have not recovered from side effects of such therapy Patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study Patients who have received prior therapy with RAD001 or other mTOR inhibitors Having any severe and/or uncontrolled medical conditions Women who are pregnant or breast feeding Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RAD001 plus paclitaxel/carboplatin<br>Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation. | Drug: RAD001<br>* Participants started RAD001 treatment with a dose of 5 mg/day once daily. A dose decrease to 5 mg every other day was allowed if tolerability issues arose.<br>* Other names: Everolimus;Drug: Paclitaxel<br>* Paclitaxel was started at doses of 175 mg/m². Dose reductions of Paclitaxel to 135 mg/m2 was permitted if tolerability issues arose.<br>Drug: Carboplatin<br>* Carboplatin was started at doses of Area under the Curve 5 (AUC 5). Dose reductions of carboplatin to AUC 4 was permitted if tolerability issues arose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Progression-free | Tumors were assessed according to Response Evaluation Criteria in Solid tumors (RECIST) to determine progression-free status. Complete response (CR): disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR): > 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD): neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; Progressive disease (PD): > 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Progression-free | Tumors were assessed according to Response Evaluation Criteria in Solid tumors (RECIST) to determine progression-free status. Complete response (CR) is disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR) is > 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD) is neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; and Progressive disease (PD is: > 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm. | 6 months | 
| Percentage of Participants With Overall Response Rate (ORR) | ORR was defined as is the proportion of participants with a best overall response of CR or PR. CR is disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response. PR is > 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions. | 3 months | 
| Percentage of Participants With Disease Control Rate (DCR) | DCR was defined as is the percentage of participants with a best overall response of CR or PR or SD. Complete response (CR) is disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR) is > 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD) is neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; and Progressive disease (PD is: > 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm. | 3 months | 
| Progression Free Survival (PFS) | PFS was defined as the time from the date of start of treatment to date of event defined as the first documented progression or death due to any cause. | 6 months | 
| Overall Survival (OS) | OS was defined as the time from date of start of treatment to date of death due to any cause. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Large cell carcinoma,, Lung cancer,, Neuroendocrine Tumors,, RAD001