Trial Outcomes & Findings for Molecular Profiling in Lung Cancer Patients (NCT NCT00191308)

NCT ID: NCT00191308

Last Updated: 2011-10-21

Results Overview

Molecular markers assessed by immunohistochemistry: thymidylate synthase, glycinamide ribonucleotide formyl transferase (GARFT), epidermal growth factor receptor (EGFR); and by polymerase chain reaction: dihydrofolate reductase (DHFR), dihydropyrimidine dehydrogenase (DPD), folylpolyglutamate synthetase (FPGS), reduced folate carrier, alpha folate receptor, Excision Repair Cross-Complementation Group 1 (ERCC1), folylpolyglutamate hydrolase (FPGH). Hypermethylated genes assessed by methylation-specific polymerase chain reaction. Due to small sample size, tumor-tissue analyses were not done.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Baseline, Cycle 2, and surgery (4-8 weeks after last dose of pemetrexed)

Results posted on

2011-10-21

Participant Flow

Participant milestones

Participant milestones
Measure	Pemetrexed + Cisplatin Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs. Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs.
Overall Study STARTED	30
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Pemetrexed + Cisplatin Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs. Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs.
Overall Study Adverse Event	1

Baseline Characteristics

Molecular Profiling in Lung Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pemetrexed + Cisplatin n=30 Participants Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs. Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs.
Age Continuous	55.94 years STANDARD_DEVIATION 8.214 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	30 participants n=5 Participants
Region of Enrollment Poland	30 participants n=5 Participants
Basis for Diagnosis Histopathological	30 participants n=5 Participants
Basis for Diagnosis Cytological	0 participants n=5 Participants
Initial Pathological Diagnosis Adenocarcinoma of Lung	2 participants n=5 Participants
Initial Pathological Diagnosis Mixed Cell Carcinoma of Lung	0 participants n=5 Participants
Initial Pathological Diagnosis Squamous Cell Carcinoma of Lung	20 participants n=5 Participants
Initial Pathological Diagnosis Large Cell Carcinoma of Lung	0 participants n=5 Participants
Initial Pathological Diagnosis Bronchoalveolar Carcinoma	0 participants n=5 Participants
Initial Pathological Diagnosis Other	8 participants n=5 Participants
Stage of Disease at Study Entry Stage IB	18 participants n=5 Participants
Stage of Disease at Study Entry Stage IIA	2 participants n=5 Participants
Stage of Disease at Study Entry Stage IIB	10 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Cycle 2, and surgery (4-8 weeks after last dose of pemetrexed)

Population: Due to lack of eligible participants, enrollment was stopped early when 30 participants were enrolled. Tumor samples were collected in only 19 of these 30 participants. Results obtained from analyses of a small number of available samples were considered to be of little scientific and medical relevance, and tumor-tissue analyses were not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Treatment start to disease progression or surgery (4-8 weeks after last dose of pemetrexed)

Population: Tumor response rate and 95% confidence interval (CI) of best CR or PR were evaluated on all qualified enrolled participants treated with at least 1 dose of study medication. Criteria=histological or cytological diagnosis of non-small cell lung cancer (NSCLC) IB-IIIA; presence of measurable disease; no previous NSCLC chemotherapy and radiotherapy.

Tumor response to treatment using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Response rate was estimated as the total number of CR or PR, divided by the total number of participants treated.

Outcome measures

Outcome measures
Measure	Pemetrexed + Cisplatin n=29 Participants Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs. Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs.
Percentage of Participants With Objective Tumor Response (Response Rate)	34.5 percentage of participants Interval 17.9 to 54.3

SECONDARY outcome

Timeframe: Time of response to disease progression (up to 44.4 months)

Population: Duration of response was analyzed on responders treated with at least 1 dose of study medication. Criteria=histological or cytological diagnosis of non-small cell lung cancer (NSCLC) IB-IIIA; presence of measurable disease; no previous NSCLC chemotherapy and radiotherapy; responder.

The duration of response was defined as the time from complete response (CR) or partial response (PR) to disease progression. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	Pemetrexed + Cisplatin n=10 Participants Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs. Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs.
Duration of Response	42.5 months Interval 8.31 to The upper limit of the 95% confidence interval (CI) was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Treatment start to disease progression or death from any cause (up to 45.5 months)

Population: DFS was evaluated on all qualified enrolled patients who received at least 1 dose of study medication. Criteria=histological or cytological diagnosis of non-small cell lung cancer (NSCLC) IB-IIIA; presence of measurable disease; no previous NSCLC chemotherapy and radiotherapy.

DFS was the time from date of first dose to first observation of progressive disease (PD) or death due to any cause. PD=20% increase in sum of longest diameter of target lesions. If a participant was not known to have died or have PD, DFS was censored at the date of the last objective progression-free disease assessment.

Outcome measures

Outcome measures
Measure	Pemetrexed + Cisplatin n=29 Participants Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs. Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs.
Disease Free Survival (DFS)	43.7 months Interval 25.36 to The upper limit of the 95% confidence interval (CI) was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Treatment start to death from any cause (up to 47.6 months)

Population: OS was evaluated on all qualified enrolled patients who received at least 1 dose of study medication.

OS was defined as the time from treatment start to death from any cause. For participants who were alive, OS was censored at the last contact date.

Outcome measures

Outcome measures
Measure	Pemetrexed + Cisplatin n=29 Participants Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs. Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs.
Overall Survival (OS)	NA months Interval 31.15 to The median and upper limit of the 95% confidence interval (CI) were not calculable because an insufficient number of participants reached the event at the final time point for assessment.

Adverse Events

Pemetrexed + Cisplatin

Serious events: 4 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pemetrexed + Cisplatin n=30 participants at risk Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs. Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs.
Gastrointestinal disorders Gastric ulcer	3.3% 1/30 • Number of events 1
Injury, poisoning and procedural complications Post procedural haemorrhage	3.3% 1/30 • Number of events 1
Respiratory, thoracic and mediastinal disorders Bronchopleural fistula	6.7% 2/30 • Number of events 2

Other adverse events

Other adverse events
Measure	Pemetrexed + Cisplatin n=30 participants at risk Pemetrexed: 500 milligram per square meter (mg/m\^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs. Cisplatin: 75 mg/m\^2 IV q 21 days for 3 cycles unless disease progression occurs.
Investigations Alanine aminotransferase increased	13.3% 4/30 • Number of events 4
Investigations Aspartate aminotransferase increased	13.3% 4/30 • Number of events 4
Investigations Weight increased	13.3% 4/30 • Number of events 4
Metabolism and nutrition disorders Hyperkalaemia	10.0% 3/30 • Number of events 3
Metabolism and nutrition disorders Hypernatraemia	6.7% 2/30 • Number of events 2
Skin and subcutaneous tissue disorders Rash	6.7% 2/30 • Number of events 2

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60