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

Phase 4

Completed

• Conditions: Carcinoma, Large Cell; Neuroendocrine Tumors
• Interventions: Drug: RAD001; Drug: Paclitaxel; Drug: Carboplatin

• Registration Number: NCT01317615
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-03-16
• Study First Submitted QC: 2011-03-16
• Study First Posted: 2011-03-17
• Study Start: 2011-04
• Primary Completion: 2015-03
• Study Completion: 2015-03
• Status Verified: 2016-02
• Results First Submitted: 2016-02-17
• Results First Submitted QC: 2016-02-29
• Last Update Submitted: 2016-02-29
• Results First Posted: 2016-03-30
• Last Update Posted: 2016-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

1. Patients who give a written informed consent obtained according to local guidelines

2. Histologically confirmed diagnosis of stage IV lung cancer of LC-NEC type according to WHO classification:

   1. Histolocial analysis of newly diagnosed disease must not be older than 8 weeks from signed consent
   2. Relapse must be confirmed by histology
   3. Neuroendocrine differentiation

3. World Health organisation (WHO) performance status grade ≤ 1

4. measurable disease

5. Adequate bone marrow function

6. Adequate liver function

7. Adequate renal function

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Exclusion Criteria

1. History or clinical evidence of central nervous system (CNS) metastases.
2. Presence of SCLC cells
3. 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)
4. 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)
5. Patients who have received any investigational drug ≤ 28 days before starting study treatment or who have not recovered from side effects of such therapy
6. 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
7. Patients who have received prior therapy with RAD001 or other mTOR inhibitors
8. Having any severe and/or uncontrolled medical conditions
9. Women who are pregnant or breast feeding

Other protocol-defined inclusion/exclusion criteria may apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RAD001 plus paclitaxel/carboplatin	RAD001	Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
RAD001 plus paclitaxel/carboplatin	Carboplatin	Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
RAD001 plus paclitaxel/carboplatin	Paclitaxel	Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Progression-free	3 months	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Overall Response Rate (ORR)	3 months	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.
Progression Free Survival (PFS)	6 months	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.
Percentage of Participants Progression-free	6 months	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.
Overall Survival (OS)	12 months	OS was defined as the time from date of start of treatment to date of death due to any cause.
Percentage of Participants With Disease Control Rate (DCR)	3 months	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.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇩🇪 Ulm, Germany