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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01317615
First received: March 16, 2011
Last updated: February 29, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Carcinoma, Large Cell
Neuroendocrine Tumors
Drug: RAD001
Drug: Paclitaxel
Drug: Carboplatin
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants Progression-free [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    OS was defined as the time from date of start of treatment to date of death due to any cause.


Enrollment: 49
Study Start Date: April 2011
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: RAD001
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.
Other Name: Everolimus
Drug: Paclitaxel
Paclitaxel was started at doses of 175 mg/m². Dose reductions of Paclitaxel to 135 mg/m2 was permitted if tolerability issues arose.
Drug: Carboplatin
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01317615

Locations
Germany
Novartis Investigative Site
Berlin, Germany, 13125
Novartis Investigative Site
Bremen, Germany, 28177
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Gauting, Germany, 82131
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Hemer, Germany, 58675
Novartis Investigative Site
Koeln, Germany, 51109
Novartis Investigative Site
Leipzig, Germany, 04177
Novartis Investigative Site
Ulm, Germany, 89081
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01317615     History of Changes
Other Study ID Numbers: CRAD001KDE37  EudraCT 2010-022273-34  2010-022273-34 
Study First Received: March 16, 2011
Results First Received: February 17, 2016
Last Updated: February 29, 2016
Health Authority: United States: Food and Drug Administration
Germany: Bundesamt für Arzneimittel und Medizinprodukte (BfArM)

Keywords provided by Novartis:
Large cell carcinoma,
Lung cancer,
Neuroendocrine Tumors,
RAD001

Additional relevant MeSH terms:
Lung Neoplasms
Neuroendocrine Tumors
Carcinoid Tumor
Carcinoma, Large Cell
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Everolimus
Sirolimus
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 22, 2016