Carcinoma, Large CellPhase 4NCT01317615
RAD001 With Paclitaxel and Carboplatin in First Line Treatment of Patients With Advanced Large Cell Lung Cancer With Neuroendocrine Differentiation
A Phase 4 study testing RAD001, Paclitaxel and Carboplatin in people with Carcinoma, Large Cell and Neuroendocrine Tumors, run by Novartis Pharmaceuticals at 9 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Large Cell, Neuroendocrine Tumors
- What is being tested?
- RAD001, Paclitaxel and Carboplatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 9 sitesGermany
- Study dates
- Apr 2011to Mar 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- measurable disease
- Adequate bone marrow function
- Adequate liver function
- Adequate renal function
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Germany9 sites
Novartis Investigative Site
Berlin, 13125
Novartis Investigative Site
Bremen, 28177
Novartis Investigative Site
Cologne, 51109
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Gauting, 82131
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Hemer, 58675
Novartis Investigative Site
Leipzig, 04177
Novartis Investigative Site
Ulm, 89081
About this study
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)
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
- Being tested
- RAD001, Paclitaxel, Carboplatin
- Keywords
- Large cell carcinoma,, Lung cancer,, Neuroendocrine Tumors,, RAD001
- Medical subject headings
- Carcinoma, Large Cell, Neuroendocrine Tumors, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Also called Everolimus
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.
PaclitaxelDrug
Paclitaxel was started at doses of 175 mg/m². Dose reductions of Paclitaxel to 135 mg/m2 was permitted if tolerability issues arose.
CarboplatinDrug
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: RAD001; Drug: Paclitaxel; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Secondary outcomes (5)
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.
Measured: 6 months
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.
Measured: 3 months
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.
Measured: 3 months
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.
Measured: 6 months
Overall Survival (OS)
OS was defined as the time from date of start of treatment to date of death due to any cause.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2011 (estimated)
- Study startApr 2011
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Large CellStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01317615
- Sponsor's protocol ID
- CRAD001KDE37
- Other IDs
- EudraCT 2010-022273-34, 2010-022273-34
- Status last verified
- Feb 2016
- First submitted
- 16 Mar 2011
- Last updated
- 30 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 28535181
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01317615
- Acronym / sponsor ID
- CRAD001KDE37
- Conditions
- Carcinoma, Large Cell, Neuroendocrine Tumors
- Keywords
- Large cell carcinoma,, Lung cancer,, Neuroendocrine Tumors,, RAD001
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 17 Mar 2011 (estimated)
- Results
- Posted 30 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 plus paclitaxel/carboplatin | Experimental | Drug: RAD001, Drug: Paclitaxel, Drug: CarboplatinParticipants received RAD001 5 mg orally once daily in combination with carboplatin and paclitaxel for a maximum 4 cycles or until discontinuation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- World Health organisation (WHO) performance status grade ≤ 1
- measurable disease
- Adequate bone marrow function
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAD001Also: EverolimusParticipants 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. | Drug | RAD001 plus paclitaxel/carboplatin |
| PaclitaxelPaclitaxel was started at doses of 175 mg/m². Dose reductions of Paclitaxel to 135 mg/m2 was permitted if tolerability issues arose. | Drug | RAD001 plus paclitaxel/carboplatin |
| CarboplatinCarboplatin 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. | Drug | RAD001 plus paclitaxel/carboplatin |
Primary outcome
Percentage of Participants Progression-free
Time frame: 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.
5 secondary outcomes
Percentage of Participants Progression-free
Time frame: 6 months
Percentage of Participants With Overall Response Rate (ORR)
Time frame: 3 months
Percentage of Participants With Disease Control Rate (DCR)
Time frame: 3 months
Progression Free Survival (PFS)
Time frame: 6 months
Overall Survival (OS)
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28535181Christopoulos 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.
Related trials for Carcinoma, Large Cell
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
RecruitingPhase 2
Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors
Metastatic Chondrosarcoma, Locally Advanced Chondrosarcoma
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma
RecruitingPhase 1
Evaluating BL-M14D1 in Subjects With Locally Advanced or Metastatic Small Cell Lung Cancer and Neuroendocrine Tumors
Small Cell Lung Cancer Metastatic or Locally Advanced, Neuroendocrine Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing RAD001, Paclitaxel and Carboplatin in people with Carcinoma, Large Cell and Neuroendocrine Tumors, run by Novartis Pharmaceuticals at 9 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Progression-free (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01317615, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2016.