Trial Outcomes & Findings for A Study of Pemetrexed/Cisplatin as Pre-operative Treatment of Early Stage Nonsquamous Non-Small Cell Lung Cancer (NCT NCT01165021)
NCT ID: NCT01165021
Last Updated: 2019-09-25
Results Overview
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.
COMPLETED
PHASE2
19 participants
From study enrollment until disease progression or recurrence up to completion of 3 cycles (21-day cycles) of chemotherapy
2019-09-25
Participant Flow
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.
Participant milestones
| Measure |
Pemetrexed + Cisplatin
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 Study
STARTED
|
19
|
|
Overall Study
≥1 Dose Chemo
|
19
|
|
Overall Study
≥1 Dose Chemo, Baseline, Cy 3 Assessment
|
17
|
|
Overall Study
3 Cycles of Chemo, Then Surgery
|
15
|
|
Overall Study
COMPLETED
|
18
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Pemetrexed + Cisplatin
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 Study
Death
|
1
|
Baseline Characteristics
A Study of Pemetrexed/Cisplatin as Pre-operative Treatment of Early Stage Nonsquamous Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Pemetrexed + Cisplatin
n=19 Participants
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
|
|---|---|
|
Age, Continuous
|
62.5 years
STANDARD_DEVIATION 9.32 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
19 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
19 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
|
15 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
|
4 participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Lung
|
17 participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Large Cell, Lung
|
1 participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Non-Small Cell, Lung
|
1 participants
n=5 Participants
|
|
Tumor-Node-Metastasis (TNM) Stage of Disease
T1aN2M0
|
3 participants
n=5 Participants
|
|
Tumor-Node-Metastasis (TNM) Stage of Disease
T1bN2M0
|
2 participants
n=5 Participants
|
|
Tumor-Node-Metastasis (TNM) Stage of Disease
T2aN2M0
|
3 participants
n=5 Participants
|
|
Tumor-Node-Metastasis (TNM) Stage of Disease
T2bN2M0
|
3 participants
n=5 Participants
|
|
Tumor-Node-Metastasis (TNM) Stage of Disease
T3N2M0
|
8 participants
n=5 Participants
|
|
Tobacco Consumption Status
Current Tobacco User
|
4 participants
n=5 Participants
|
|
Tobacco Consumption Status
Former Tobacco User
|
12 participants
n=5 Participants
|
|
Tobacco Consumption Status
Never Used Tobacco
|
3 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From study enrollment until disease progression or recurrence up to completion of 3 cycles (21-day cycles) of chemotherapyPopulation: Participants who received at least 1 dose of preoperative chemotherapy and had baseline and Cycle 3 scans for tumor assessment.
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.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=17 Participants
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
|
|---|---|
|
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
|
41.2 percentage of participants
Interval 18.4 to 67.1
|
SECONDARY outcome
Timeframe: At the time of surgery (within 3 to 6 weeks of Day 1 of Cycle 3 [21-day cycles] of chemotherapy)Population: Participants who received at least 1 dose of preoperative chemotherapy and had surgical tumor tissue samples available.
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.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=15 Participants
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
|
|---|---|
|
Percentage of Participants With No Viable Tumor Cells in Resected Lung Tissue [Pathological Complete Remission (pCR)]
|
93.3 percentage of participants
Interval 68.1 to 99.8
|
SECONDARY outcome
Timeframe: From study enrollment until disease progression or recurrence up to completion of 3 cycles (21-day cycles) of chemotherapyPopulation: Participants who received at least 1 dose of preoperative chemotherapy and had baseline and Cycle 3 scans for tumor assessment.
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.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=17 Participants
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
|
|---|---|
|
Percentage of Participants Who Exhibit a Downward Shift in Tumor Extent From Stage IIIAN2 to Stages IIIA, II, I, or Stage 0
Change to Stage IIIA
|
29.4 percentage of participants
Interval 10.3 to 56.0
|
|
Percentage of Participants Who Exhibit a Downward Shift in Tumor Extent From Stage IIIAN2 to Stages IIIA, II, I, or Stage 0
No Change or Worsening of Tumor Stage
|
29.4 percentage of participants
Interval 10.3 to 56.0
|
|
Percentage of Participants Who Exhibit a Downward Shift in Tumor Extent From Stage IIIAN2 to Stages IIIA, II, I, or Stage 0
Change to Stage II
|
11.8 percentage of participants
Interval 1.5 to 36.4
|
|
Percentage of Participants Who Exhibit a Downward Shift in Tumor Extent From Stage IIIAN2 to Stages IIIA, II, I, or Stage 0
Change to Stage I
|
17.6 percentage of participants
Interval 3.8 to 43.4
|
|
Percentage of Participants Who Exhibit a Downward Shift in Tumor Extent From Stage IIIAN2 to Stages IIIA, II, I, or Stage 0
Missing
|
11.8 percentage of participants
Interval 1.5 to 36.4
|
SECONDARY outcome
Timeframe: Enrollment until the date of death from any cause up to 64 monthsPopulation: All participants who received 1 or more doses of preoperative chemotherapy. Participants censored=8
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.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=19 Participants
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 Survival (OS)
|
34.6 months
Interval 10.8 to
Upper range of 95% confidence interval were not calculated due to high censoring rate.
|
SECONDARY outcome
Timeframe: Enrollment until the first date of objectively determined PD or death up to 64 monthsPopulation: All participants who received 1 or more doses of preoperative chemotherapy. Participants censored=3.
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.
Outcome measures
| Measure |
Pemetrexed + Cisplatin
n=19 Participants
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
|
|---|---|
|
Progression-Free Survival (PFS)
|
12.4 months
Interval 7.0 to 21.7
|
Adverse Events
Pemetrexed + Cisplatin
Serious adverse events
| Measure |
Pemetrexed + Cisplatin
n=19 participants at risk
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
|
|---|---|
|
Gastrointestinal disorders
Acute abdomen
|
5.3%
1/19 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Paraneoplastic syndrome
|
5.3%
1/19 • Number of events 1
|
Other adverse events
| Measure |
Pemetrexed + Cisplatin
n=19 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.5%
2/19 • Number of events 2
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.3%
1/19 • Number of events 1
|
|
Eye disorders
Lacrimation increased
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Apical granuloma
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
10.5%
2/19 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhoea
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Dysphagia
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
21.1%
4/19 • Number of events 5
|
|
Gastrointestinal disorders
Oral dysaesthesia
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Stomatitis
|
15.8%
3/19 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
1/19 • Number of events 1
|
|
General disorders
Asthenia
|
15.8%
3/19 • Number of events 3
|
|
General disorders
Fatigue
|
21.1%
4/19 • Number of events 7
|
|
General disorders
Irritability
|
5.3%
1/19 • Number of events 1
|
|
General disorders
Oedema peripheral
|
5.3%
1/19 • Number of events 1
|
|
General disorders
Pyrexia
|
15.8%
3/19 • Number of events 3
|
|
Infections and infestations
Bronchitis
|
5.3%
1/19 • Number of events 1
|
|
Infections and infestations
Herpes zoster
|
5.3%
1/19 • Number of events 1
|
|
Infections and infestations
Tooth abscess
|
5.3%
1/19 • Number of events 1
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
5.3%
1/19 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
21.1%
4/19 • Number of events 6
|
|
Investigations
Platelet count decreased
|
10.5%
2/19 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.3%
1/19 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.3%
1/19 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
5.3%
1/19 • Number of events 1
|
|
Nervous system disorders
Headache
|
5.3%
1/19 • Number of events 1
|
|
Nervous system disorders
Syncope
|
10.5%
2/19 • Number of events 2
|
|
Psychiatric disorders
Depression
|
5.3%
1/19 • Number of events 1
|
|
Psychiatric disorders
Depressive symptom
|
5.3%
1/19 • Number of events 1
|
|
Renal and urinary disorders
Cystitis noninfective
|
5.3%
1/19 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.3%
1/19 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Cafe au lait spots
|
5.3%
1/19 • Number of events 1
|
|
Vascular disorders
Hypotension
|
15.8%
3/19 • Number of events 3
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60