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

NCT01317615 | Completed Phase 4 Results

• 3 other identifiers: CRAD001KDE37EudraCT 2010-022273-342010-022273-34
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 9

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.

Conditions

Carcinoma, Large Cell; Neuroendocrine Tumors

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Percentage of Participants Progression-free

  6 months

• Percentage of Participants With Overall Response Rate (ORR)

  3 months

• Percentage of Participants With Disease Control Rate (DCR)

  3 months

• Progression Free Survival (PFS)

  6 months

• Overall Survival (OS)

  12 months

Study Arms (1)

RAD001 plus paclitaxel/carboplatin

EXPERIMENTAL

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

Drug: RAD001; Drug: Paclitaxel; Drug: Carboplatin

Interventions

RAD001 DRUG

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.

Also known as: Everolimus

RAD001 plus paclitaxel/carboplatin

Paclitaxel DRUG

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

RAD001 plus paclitaxel/carboplatin

Carboplatin DRUG

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.

RAD001 plus paclitaxel/carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

Berlin, 13125, Germany

Location

Novartis Investigative Site

Bremen, 28177, Germany

Location

Novartis Investigative Site

Cologne, 51109, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Gauting, 82131, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Hemer, 58675, Germany

Location

Novartis Investigative Site

Leipzig, 04177, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Related Publications (1)

• 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.

  PMID: 28535181 DERIVED

MeSH Terms

Conditions

Carcinoma, Large Cell; Neuroendocrine Tumors; Lung Neoplasms

Interventions

Everolimus; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2011
• First Posted: March 17, 2011
• Study Start: April 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 30, 2016
• Results First Posted: March 30, 2016

Record last verified: 2016-02

Locations

DE (9)