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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00789373




Registration number
NCT00789373
Ethics application status
Date submitted
10/11/2008
Date registered
11/11/2008
Date last updated
14/12/2018

Titles & IDs
Public title
A Study of Induction and Maintenance Treatment of Advanced Non-squamous Non-Small Cell Lung Cancer
Scientific title
A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed Plus Best Supportive Care Versus Best Supportive Care Immediately Following Induction Treatment With Pemetrexed + Cisplatin for Advanced Non-squamous Non-Small Cell Lung Cancer.
Secondary ID [1] 0 0
H3E-EW-S124
Secondary ID [2] 0 0
12560
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Cisplatin
Treatment: Drugs - Placebo
Treatment: Drugs - Pemetrexed
Other interventions - Best Supportive Care

Experimental: pemetrexed + cisplatin followed by pemetrexed - pemetrexed plus cisplatin followed by pemetrexed plus best supportive care

Placebo Comparator: pemetrexed + cisplatin followed by placebo - pemetrexed plus cisplatin followed by placebo plus best supportive care


Treatment: Drugs: Pemetrexed
Induction therapy: 500 mg/m^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles

Treatment: Drugs: Cisplatin
Induction therapy: Cisplatin: 75 mg/m^2, IV, on Day 1 of each 21-day cycle for 4 cycles

Treatment: Drugs: Placebo
Maintenance therapy: Normal saline (0.9% sodium chloride) administered IV on Day 1 every 21-day cycle until progressive disease or treatment discontinuation

Treatment: Drugs: Pemetrexed
Maintenance therapy: 500 mg/m^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation.

Other interventions: Best Supportive Care
Best Supportive Care is treatment given with the intent to maximize quality of life. Best Supportive Care excludes any treatment in which the goal is to cure or slow the progression of the study disease. Patients will receive Best Supportive Care as judged by their treating physician. Those therapies considered acceptable include, but are not limited to, palliative radiation to extrathoracic structures, antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support (enteral or parenteral).

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Investigator-assessed Objective Progression-free Survival (PFS) - Investigator-assessed objective PFS was measured from the date of randomization to the first date of objectively determined progressive disease (PD) or death from any cause. For patients not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of last objective tumor assessment. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions.
Timepoint [1] 0 0
Date of randomization to the date of measured PD or date of death from any cause (up to 19.3 months)
Secondary outcome [1] 0 0
Independently-assessed Objective Progression-free Survival (PFS) - To further evaluate the robustness of the PFS analysis, Lilly established an independent review of PFS to assess the potential for investigator bias in the determination of objective PD. PFS was measured from the date of randomization to the first date of objectively determined PD or death. For patients alive as of the data cutoff date and who did not have PD, PFS was censored at the date of the last objective tumor assessment. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions.
Timepoint [1] 0 0
Date of randomization to first date of measured PD or date of death from any cause (up to 19.3 months)
Secondary outcome [2] 0 0
Overall Survival (OS) - OS is the duration from enrollment to death. For patients who are alive, OS is censored at the last contact.
Timepoint [2] 0 0
Date of randomization to the date of death from any cause up to 39.5 months
Secondary outcome [3] 0 0
Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score - The EQ-5D is a generic instrument that describes health status in 5 attributes (mobility, self-care, pain/discomfort, anxiety/depression, usual activities) using a three level scale (no problem, some problems, and major problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score range from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension).
Timepoint [3] 0 0
Baseline randomization through 30-day post-discontinuation visit (up to 19.3 months)
Secondary outcome [4] 0 0
Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS) - Patients indicate their present health state through completion of the VAS. Possible scores range from 0 (worst imaginable health state) to 100 (best imaginable health state).
Timepoint [4] 0 0
Baseline randomization through 30-day post-discontinuation visit (up to 19.3 months)
Secondary outcome [5] 0 0
Percentage of Participants With Hospitalizations Due to Adverse Events or Requiring Transfusion (Resource Utilization)
Timepoint [5] 0 0
Baseline randomization through 30-day post-discontinuation visit (up to 19.3 months)
Secondary outcome [6] 0 0
Percentage of Participants With a Non-Serious Adverse Event (AE) During Maintenance Phase - A summary of non-serious AEs is located in the Reported Adverse Event Module.
Timepoint [6] 0 0
Baseline randomization through 30-day post-discontinuation visit (up to 49.7 months)
Secondary outcome [7] 0 0
Percentage of Participants With Serious Adverse Events During Maintenance Phase - A summary of serious adverse events is located in the Reported Adverse Event Module.
Timepoint [7] 0 0
Baseline randomization through 30-day post-discontinuation visit (up to 49.7 months)
Secondary outcome [8] 0 0
Percentage of Participants With Objective Tumor Response (Response Rate) During Maintenance Phase of Study up to Primary Data Cut-Off - Analysis for combined phases was not performed since response was calculated separately for each phase of study. Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response(PR)is at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease(PD) is at least a 20% increase in sum of longest diameter of target lesions; Stable Disease(SD)=no change or small changes that do not meet the above criteria for CR, PR, or PD.
Timepoint [8] 0 0
Baseline to date of measured progressive disease (up to 19.3 months)
Secondary outcome [9] 0 0
Percentage of Participants With Independently-Assessed Objective Tumor Response (Response Rate) During Maintenance Phase Up to Primary Data Cut-Off - Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) is at least a 20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=no change or small changes that do not meet the above criteria for CR, PR, or PD. Response Rate = (CR+PR)/Participants in Arm*100. Disease Control Rate=(CR+PR+SD)/Number of Participants in Arm*100.
Timepoint [9] 0 0
Date of randomization to date of measured PD (up to 19.3 months)

Eligibility
Key inclusion criteria
Inclusion Criteria for the Induction Phase:

- You must sign an informed consent document for clinical research.

- You must have Stage IIIB or IV nonsquamous Non-Small Cell Lung Cancer.

- You must at least be able to be physically mobile, take care of yourself, and must be
up and about and able to perform light activities such as light housework or office
work.

- You are allowed to have had prior radiation therapy as long as it was not to more than
25% of the bone marrow and did not include the whole pelvis. Thoracic radiation must
be completed more than 30 days before the study. You must be recovered from the toxic
effects (except hair loss).

- You must have at least 1 measurable tumor lesion according to the Response Evaluation
Criteria in Solid Tumors (RECIST) guidelines or disease that can be evaluated by
computed tomography (CT) Scan.

- Your test results assessing the function of your blood forming tissue, kidneys, and
liver must be satisfactory.

- You must be 18 years of age or older.

- Women must be sterile, postmenopausal or on contraception and men must be on
contraception or sterile (e.g. post-vasectomy).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for the Induction Phase:

- You cannot have squamous cell and/or mixed small cell, non-small cell lung cancer

- You cannot have received other investigational drugs within the last 30 days of
entering the trial.

- You cannot have previously completed or withdrawn from this study or any other study
investigating pemetrexed.

- You cannot have other serious on-going illnesses including active infections.

- You cannot have a serious cardiac condition, such as a heart attack, angina, or heart
disease within 6 months of entering the trial.

- You cannot have had another form of cancer other than superficial basal cell and
superficial squamous (skin) cell cancer, or carcinoma in situ of the cervix within the
last 5 years. Patients with a history of low-grade (Gleason score less than or equal
to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years
ago.

- You cannot have known central nervous system (CNS) metastases, other than treated,
stable brain metastasis.

- You cannot be receiving nor have received any prior systemic anticancer therapy for
lung cancer (including chemotherapy given after surgery in early-stage treatment).

- You cannot have clinically significant third-space fluid collections (e.g. ascites or
pleural effusions that cannot be controlled by drainage or other procedures).

- You cannot have received a recent (within 30 days) or are receiving a yellow fever
vaccination.

- You are unable to stop taking more than 1.3 grams of aspirin on a daily basis or other
non-steroidal anti-inflammatory drugs (NSAIDs).

- You are unable or unwilling to take folic acid, injections of vitamin B12, or
corticosteroids.

- You cannot be pregnant or breastfeeding.

Inclusion criteria at Randomization for the Maintenance Phase:

- You must at least be able to be physically mobile, take care of yourself, and must be
up and about and able to perform light activities such as light housework or office
work.

- You must have documented radiographic evidence of a tumor response of complete
response (CR), partial response (PR), or stable disease (SD) according to the Response
Evaluation Criteria in Solid Tumors (RECIST) guidelines. Tumor assessment must occur
between Cycle 4 (Day 1) of induction therapy and the date of randomization. This
response does not have to be confirmed in order for the patient to be randomized to
the maintenance phase.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Adelaide
Recruitment hospital [2] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Frankston
Recruitment hospital [3] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Wendouree
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3199 - Frankston
Recruitment postcode(s) [3] 0 0
3355 - Wendouree
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Aalst
Country [2] 0 0
Belgium
State/province [2] 0 0
Brussels
Country [3] 0 0
Belgium
State/province [3] 0 0
Genk
Country [4] 0 0
Belgium
State/province [4] 0 0
Gilly
Country [5] 0 0
Belgium
State/province [5] 0 0
Liege
Country [6] 0 0
Belgium
State/province [6] 0 0
Sint Niklaas
Country [7] 0 0
Finland
State/province [7] 0 0
Espoo
Country [8] 0 0
Finland
State/province [8] 0 0
Helsinki
Country [9] 0 0
Finland
State/province [9] 0 0
Tampere
Country [10] 0 0
Finland
State/province [10] 0 0
Turku
Country [11] 0 0
France
State/province [11] 0 0
Avignon
Country [12] 0 0
France
State/province [12] 0 0
Dijon
Country [13] 0 0
France
State/province [13] 0 0
Le Mans Cedex 1
Country [14] 0 0
France
State/province [14] 0 0
Montpellier
Country [15] 0 0
France
State/province [15] 0 0
Nantes
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
France
State/province [17] 0 0
Vandoeuvre Les Nancy
Country [18] 0 0
France
State/province [18] 0 0
Vandoeuvre-Les-Nancy
Country [19] 0 0
Germany
State/province [19] 0 0
Frankfurt
Country [20] 0 0
Germany
State/province [20] 0 0
Gerlingen
Country [21] 0 0
Germany
State/province [21] 0 0
Großhansdorf
Country [22] 0 0
Germany
State/province [22] 0 0
Hamburg
Country [23] 0 0
Germany
State/province [23] 0 0
Heidelberg
Country [24] 0 0
Germany
State/province [24] 0 0
Ulm
Country [25] 0 0
Greece
State/province [25] 0 0
Athens
Country [26] 0 0
Greece
State/province [26] 0 0
Chania
Country [27] 0 0
Greece
State/province [27] 0 0
Neo Faliro
Country [28] 0 0
Greece
State/province [28] 0 0
Patras
Country [29] 0 0
India
State/province [29] 0 0
Bangalore
Country [30] 0 0
India
State/province [30] 0 0
Bhopal
Country [31] 0 0
India
State/province [31] 0 0
Madurai
Country [32] 0 0
India
State/province [32] 0 0
Mumbai
Country [33] 0 0
India
State/province [33] 0 0
Patna
Country [34] 0 0
Italy
State/province [34] 0 0
Avellino
Country [35] 0 0
Italy
State/province [35] 0 0
Aviano
Country [36] 0 0
Italy
State/province [36] 0 0
Genova
Country [37] 0 0
Italy
State/province [37] 0 0
Lido Di Camaiore
Country [38] 0 0
Italy
State/province [38] 0 0
Monza
Country [39] 0 0
Italy
State/province [39] 0 0
Pisa
Country [40] 0 0
Italy
State/province [40] 0 0
Reggio Emilia
Country [41] 0 0
Italy
State/province [41] 0 0
Rome
Country [42] 0 0
Italy
State/province [42] 0 0
Udine
Country [43] 0 0
Netherlands
State/province [43] 0 0
Ede
Country [44] 0 0
Netherlands
State/province [44] 0 0
Groningen
Country [45] 0 0
Netherlands
State/province [45] 0 0
Harderwijk
Country [46] 0 0
Netherlands
State/province [46] 0 0
Heerlen
Country [47] 0 0
Poland
State/province [47] 0 0
Poznan
Country [48] 0 0
Poland
State/province [48] 0 0
Warsaw
Country [49] 0 0
Portugal
State/province [49] 0 0
Coimbra
Country [50] 0 0
Portugal
State/province [50] 0 0
Lisbon
Country [51] 0 0
Portugal
State/province [51] 0 0
Vila Franca De Xira
Country [52] 0 0
Romania
State/province [52] 0 0
Bucharest
Country [53] 0 0
Romania
State/province [53] 0 0
Cluj-Napoca
Country [54] 0 0
Romania
State/province [54] 0 0
Oradea
Country [55] 0 0
Spain
State/province [55] 0 0
Manresa
Country [56] 0 0
Spain
State/province [56] 0 0
Sabadell
Country [57] 0 0
Spain
State/province [57] 0 0
Sevilla
Country [58] 0 0
Spain
State/province [58] 0 0
Valencia
Country [59] 0 0
Spain
State/province [59] 0 0
Zaragoza
Country [60] 0 0
Turkey
State/province [60] 0 0
Bornova
Country [61] 0 0
Turkey
State/province [61] 0 0
Sihhiye
Country [62] 0 0
Turkey
State/province [62] 0 0
Zeytinburnu
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Scotland
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Surrey
Country [65] 0 0
United Kingdom
State/province [65] 0 0
West Midlands
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Newcastle

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will compare progression-free survival in patients with advanced non-squamous
non-small cell lung cancer. Patients who do not progress following 4 cycles of induction
treatment with pemetrexed and cisplatin will be randomized 2:1 to receive either maintenance
pemetrexed or placebo.
Trial website
https://clinicaltrials.gov/show/NCT00789373
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications