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

Primary Purpose

Carcinoma, Large Cell, Neuroendocrine Tumors

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
RAD001
Paclitaxel
Carboplatin
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Large Cell focused on measuring Large cell carcinoma,, Lung cancer,, Neuroendocrine Tumors,, RAD001

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001 plus paclitaxel/carboplatin

Arm Description

Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
Overall Survival (OS)
OS was defined as the time from date of start of treatment to date of death due to any cause.

Full Information

First Posted
March 16, 2011
Last Updated
February 29, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01317615
Brief Title
RAD001 With Paclitaxel and Carboplatin in First Line Treatment of Patients With Advanced Large Cell Lung Cancer With Neuroendocrine Differentiation
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Large Cell, Neuroendocrine Tumors
Keywords
Large cell carcinoma,, Lung cancer,, Neuroendocrine Tumors,, RAD001

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RAD001 plus paclitaxel/carboplatin
Arm Type
Experimental
Arm Description
Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.
Intervention Type
Drug
Intervention Name(s)
RAD001
Other Intervention Name(s)
Everolimus
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Paclitaxel was started at doses of 175 mg/m². Dose reductions of Paclitaxel to 135 mg/m2 was permitted if tolerability issues arose.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants Progression-free
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Percentage of Participants Progression-free
Description
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.
Time Frame
6 months
Title
Percentage of Participants With Overall Response Rate (ORR)
Description
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.
Time Frame
3 months
Title
Percentage of Participants With Disease Control Rate (DCR)
Description
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.
Time Frame
3 months
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
6 months
Title
Overall Survival (OS)
Description
OS was defined as the time from date of start of treatment to date of death due to any cause.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Novartis Investigative Site
City
Bremen
ZIP/Postal Code
28177
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Gauting
ZIP/Postal Code
82131
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Hemer
ZIP/Postal Code
58675
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
51109
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04177
Country
Germany
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89081
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
28535181
Citation
Christopoulos P, Engel-Riedel W, Grohe C, Kropf-Sanchen C, von Pawel J, Gutz S, Kollmeier J, Eberhardt W, Ukena D, Baum V, Nimmrich I, Sieder C, Schnabel PA, Serke M, Thomas M. Everolimus with paclitaxel and carboplatin as first-line treatment for metastatic large-cell neuroendocrine lung carcinoma: a multicenter phase II trial. Ann Oncol. 2017 Aug 1;28(8):1898-1902. doi: 10.1093/annonc/mdx268.
Results Reference
derived

Learn more about this trial

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

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