Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Pemetrexed/Cisplatin as Pre-operative Treatment of Early Stage Nonsquamous Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01165021
Recruitment Status : Completed
First Posted : July 19, 2010
Results First Posted : May 21, 2014
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non Small Cell Lung Cancer
Interventions Drug: Pemetrexed
Drug: Cisplatin
Drug: Folic Acid
Drug: Vitamin B12
Drug: Dexamethasone
Enrollment 19
Recruitment Details  
Pre-assignment Details Participant Flow reports participants who discontinued from study treatment. Completed participants were those who had a baseline tumor assessment, finished 3 cycles (Cy) of pre-operative chemotherapy (chemo), and had a second tumor assessment following chemo.
Arm/Group Title Pemetrexed + Cisplatin
Hide Arm/Group Description

Pemetrexed: 500 milligrams per square meter (mg/m²) administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Cisplatin: 75 mg/m² administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Period Title: Overall Study
Started 19
≥1 Dose Chemo 19
≥1 Dose Chemo, Baseline, Cy 3 Assessment 17
3 Cycles of Chemo, Then Surgery 15
Completed 18
Not Completed 1
Reason Not Completed
Death             1
Arm/Group Title Pemetrexed + Cisplatin
Hide Arm/Group Description

Pemetrexed: 500 milligrams per square meter (mg/m²) administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Cisplatin: 75 mg/m² administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of chemotherapy.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants
62.5  (9.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
6
  31.6%
Male
13
  68.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White Number Analyzed 19 participants
19
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Italy Number Analyzed 19 participants
19
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants
0 15
1 4
[1]
Measure Description: ECOG classifies participants according to their functional impairment. Scores range from 0 (fully active) to 5 (death). 0 (fully active, able to carry on all pre-disease performance without restriction) and 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature).
Initial Pathological Diagnosis   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants
Adenocarcinoma, Lung 17
Carcinoma, Large Cell, Lung 1
Carcinoma, Non-Small Cell, Lung 1
[1]
Measure Description: Initial cancer diagnosis confirmed by tissue biopsy.
Tumor-Node-Metastasis (TNM) Stage of Disease   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants
T1aN2M0 3
T1bN2M0 2
T2aN2M0 3
T2bN2M0 3
T3N2M0 8
[1]
Measure Description: Tumor size: T1=surrounded by lung or visceral pleura with no evidence of invasion more proximal than lobar bronchus; T1a ≤2 centimeters (cm) at greatest dimension (GD); T1b >2 cm, ≤3 cm at GD; T2=involves main bronchus, ≥2 cm distal to carina; invades visceral pleura, associated with atelectasis or obstructive pneumonitis extends to hilar but not entire lung; T2a >3 cm, ≤5 cm at GD; T2b >5 cm, ≤7 cm at GD; T3= >7 cm or 1 that invades the thoracic cavity. Nodal status (N): N2 =Metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes. Distant metastasis (M): M0 =No distant metastasis.
Tobacco Consumption Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants
Current Tobacco User 4
Former Tobacco User 12
Never Used Tobacco 3
1.Primary Outcome
Title Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
Hide Description Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size [<10 millimeter (mm) short axis]. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameters. ORR calculated as: (sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100.
Time Frame From study enrollment until disease progression or recurrence up to completion of 3 cycles (21-day cycles) of chemotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of preoperative chemotherapy and had baseline and Cycle 3 scans for tumor assessment.
Arm/Group Title Pemetrexed + Cisplatin
Hide Arm/Group Description:

Pemetrexed: 500 milligrams per square meter (mg/m²) administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Cisplatin: 75 mg/m² administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Overall Number of Participants Analyzed 17
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.2
(18.4 to 67.1)
2.Secondary Outcome
Title Percentage of Participants With No Viable Tumor Cells in Resected Lung Tissue [Pathological Complete Remission (pCR)]
Hide Description pCR after the participant has undergone surgery was calculated as: (total number of participants with pCR) divided by (the total number of participants in pathological response population) multiplied by 100.
Time Frame At the time of surgery (within 3 to 6 weeks of Day 1 of Cycle 3 [21-day cycles] of chemotherapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of preoperative chemotherapy and had surgical tumor tissue samples available.
Arm/Group Title Pemetrexed + Cisplatin
Hide Arm/Group Description:

Pemetrexed: 500 milligrams per square meter (mg/m²) administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Cisplatin: 75 mg/m² administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Overall Number of Participants Analyzed 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
93.3
(68.1 to 99.8)
3.Secondary Outcome
Title Percentage of Participants Who Exhibit a Downward Shift in Tumor Extent From Stage IIIAN2 to Stages IIIA, II, I, or Stage 0
Hide Description Tumor downstaging compared to baseline (Stage IIIAN2) were those participants who exhibited a downward shift in tumor extent from Stage IIIAN2 to Stages IIIA, II, I, or 0 were reported. Downstaging was based on radiological examination. Stage IIIAN2 was locally advanced and/or involved lymph nodes, metastasis in ipsilateral mediastinal and or subcarinal lymph nodes, tumors were ≤2 centimeters (cm) up to 5 cm in greatest dimension; Stage IIIA was locally advanced and/or involved lymph nodes, tumor extension was restricted to the affected lung; Stage II was locally advanced and/or involved lymph nodes; Stage I was small localized cancers, usually curable; Stage 0 the cancer did not spread beyond the inner lining of the lung. Missing responses were also reported. Percentage of participants calculated as: (number of participants with a downward shift in extent of their tumor) divided by (total number of evaluable participants) multiplied by 100.
Time Frame From study enrollment until disease progression or recurrence up to completion of 3 cycles (21-day cycles) of chemotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of preoperative chemotherapy and had baseline and Cycle 3 scans for tumor assessment.
Arm/Group Title Pemetrexed + Cisplatin
Hide Arm/Group Description:

Pemetrexed: 500 milligrams per square meter (mg/m²) administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Cisplatin: 75 mg/m² administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Overall Number of Participants Analyzed 17
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
No Change or Worsening of Tumor Stage
29.4
(10.3 to 56.0)
Change to Stage IIIA
29.4
(10.3 to 56.0)
Change to Stage II
11.8
(1.5 to 36.4)
Change to Stage I
17.6
(3.8 to 43.4)
Missing
11.8
(1.5 to 36.4)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as duration from the date of study enrollment to the date of death from any cause. Participants not known to have died as of the data inclusion cut-off date were censored at the date of last contact. The last contact for participants in post-discontinuation was the last date participant was known to be alive.
Time Frame Enrollment until the date of death from any cause up to 64 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received 1 or more doses of preoperative chemotherapy. Participants censored=8
Arm/Group Title Pemetrexed + Cisplatin
Hide Arm/Group Description:

Pemetrexed: 500 milligrams per square meter (mg/m²) administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Cisplatin: 75 mg/m² administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Overall Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: months
34.6 [1] 
(10.8 to NA)
[1]
Upper range of 95% confidence interval were not calculated due to high censoring rate.
5.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS was defined as the time from date of first dose to the first observation of disease progression or death due to any cause. For participants not known to have died or did not have objective progressive disease (PD) as of the data inclusion cut-off date, PFS was censored at the date of the last objective progression-free disease assessment. PD was defined using RECIST v1.1 criteria as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time Frame Enrollment until the first date of objectively determined PD or death up to 64 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received 1 or more doses of preoperative chemotherapy. Participants censored=3.
Arm/Group Title Pemetrexed + Cisplatin
Hide Arm/Group Description:

Pemetrexed: 500 milligrams per square meter (mg/m²) administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Cisplatin: 75 mg/m² administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Overall Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: months
12.4
(7.0 to 21.7)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pemetrexed + Cisplatin
Hide Arm/Group Description

Pemetrexed: 500 milligram per square meter (mg/m²) administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

Cisplatin: 75 mg/m² administered as an intravenous infusion on Day 1 of 21-day cycles, for 3 cycles

All-Cause Mortality
Pemetrexed + Cisplatin
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Pemetrexed + Cisplatin
Affected / at Risk (%) # Events
Total   2/19 (10.53%)    
Gastrointestinal disorders   
Acute abdomen  1  1/19 (5.26%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Paraneoplastic syndrome  1  1/19 (5.26%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pemetrexed + Cisplatin
Affected / at Risk (%) # Events
Total   15/19 (78.95%)    
Blood and lymphatic system disorders   
Anaemia  1  2/19 (10.53%)  2
Neutropenia  1  1/19 (5.26%)  1
Eye disorders   
Lacrimation increased  1  1/19 (5.26%)  1
Gastrointestinal disorders   
Abdominal pain  1  1/19 (5.26%)  1
Abdominal pain upper  1  1/19 (5.26%)  1
Apical granuloma  1  1/19 (5.26%)  1
Constipation  1  2/19 (10.53%)  2
Diarrhoea  1  1/19 (5.26%)  1
Dysphagia  1  1/19 (5.26%)  1
Haemorrhoids  1  1/19 (5.26%)  1
Nausea  1  4/19 (21.05%)  5
Oral dysaesthesia  1  1/19 (5.26%)  1
Stomatitis  1  3/19 (15.79%)  3
Vomiting  1  1/19 (5.26%)  1
General disorders   
Asthenia  1  3/19 (15.79%)  3
Fatigue  1  4/19 (21.05%)  7
Irritability  1  1/19 (5.26%)  1
Oedema peripheral  1  1/19 (5.26%)  1
Pyrexia  1  3/19 (15.79%)  3
Infections and infestations   
Bronchitis  1  1/19 (5.26%)  1
Herpes zoster  1  1/19 (5.26%)  1
Tooth abscess  1  1/19 (5.26%)  1
Injury, poisoning and procedural complications   
Anaemia postoperative  1  1/19 (5.26%)  1
Investigations   
Neutrophil count decreased  1  4/19 (21.05%)  6
Platelet count decreased  1  2/19 (10.53%)  2
Musculoskeletal and connective tissue disorders   
Myalgia  1  1/19 (5.26%)  1
Pain in extremity  1  1/19 (5.26%)  1
Nervous system disorders   
Dysgeusia  1  1/19 (5.26%)  1
Headache  1  1/19 (5.26%)  1
Syncope  1  2/19 (10.53%)  2
Psychiatric disorders   
Depression  1  1/19 (5.26%)  1
Depressive symptom  1  1/19 (5.26%)  1
Renal and urinary disorders   
Cystitis noninfective  1  1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  1/19 (5.26%)  1
Skin and subcutaneous tissue disorders   
Cafe au lait spots  1  1/19 (5.26%)  1
Vascular disorders   
Hypotension  1  3/19 (15.79%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Due to difficulties identifying suitable participants and enrollment delays, entries were closed after 26 of planned 33 participants signed consent. Results based on 19 participants who received ≥1 dose of chemotherapy. View results with caution.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01165021    
Other Study ID Numbers: 13621
H3E-EW-JMIP ( Other Identifier: Eli Lilly and Company )
First Submitted: July 14, 2010
First Posted: July 19, 2010
Results First Submitted: April 23, 2014
Results First Posted: May 21, 2014
Last Update Posted: September 25, 2019