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

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)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01317615

Enrollment

Registered

2011-03-17

Start date

2011-04-30

Completion date

2015-03-31

Last updated

2016-03-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Carcinoma, Large Cell, Neuroendocrine Tumors

Keywords

Large cell carcinoma,, Lung cancer,, Neuroendocrine Tumors,, RAD001

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.

Interventions

DRUGRAD001

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.

DRUGPaclitaxel

Paclitaxel was started at doses of 175 mg/m². Dose reductions of Paclitaxel to 135 mg/m2 was permitted if tolerability issues arose.

DRUGCarboplatin

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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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/

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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.
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.
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.

Countries

Germany

Participant flow

Recruitment details

This was an open-label, single arm study.

Participants by arm

Arm	Count
RAD001 Plus Paclitaxel/Carboplatin Participants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation.	49
Total	49

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Abnormal laboratory value(s)	1
Overall Study	Adverse Event	7
Overall Study	Death	6
Overall Study	Disease progression	25
Overall Study	New cancer therapy	5
Overall Study	Withdrawal by Subject	5

Baseline characteristics

Characteristic	RAD001 Plus Paclitaxel/Carboplatin
Age, Continuous	62 Years STANDARD_DEVIATION 8.9
Sex: Female, Male Female	14 Participants
Sex: Female, Male Male	35 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	43 / 49
serious Total, serious adverse events	28 / 49

Outcome results

Primary

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.

Time frame: 3 months