Pemetrexed-Carboplatin and Gemcitabine-Vinorelbine in Advanced Breast Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00325234
• Collaborator: (none)
• Enrollment: 135
• Locations: 22
• Arms: 2
• Duration (Months): 50
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary purpose of this study is to help answer the following research questions:

• whether the chemotherapy combination therapy Pemetrexed-Carboplatin or Gemcitabine-Vinorelbine can help participants with advanced breast cancer to make the tumor smaller or disappear and for how long

• to learn more about the side effects in each chemotherapy combination treatment arm

• to assess how participants with advanced breast cancer report health changes while receiving any of the chemotherapy combination arm

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Pemetrexed; Drug: Carboplatin; Drug: Gemcitabine; Drug: Vinorelbine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Two Chemotherapy Regimens, Pemetrexed-Carboplatin, and Gemcitabine-Vinorelbine, in Anthracycline and Taxanes Pretreated Advanced Breast Cancer Patients
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pemetrexed/Carboplatin Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC (Area under the plasma drug concentration versus time curve) 5.0 mg*min/mL. The cycle of treatment was 21 days.	Drug: Pemetrexed; 600 mg/m^2, administered intravenously (IV) every 21 days until disease progression or unacceptable toxicity.; Other Names: LY231514 Alimta ; Drug: Carboplatin; AUC 5 mg*min/mL, administered IV every 21 days until disease progression or unacceptable toxicity.
Active Comparator: Gemcitabine/Vinorelbine Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.	Drug: Gemcitabine; 1200 mg/m^2 gemcitabine, administered IV on day 1 and day 8 every 21 days until disease progression or unacceptable toxicity.; Other Names: LY188011 Gemzar ; Drug: Vinorelbine; 30 mg/m^2 vinorelbine administered IV on day 1 and day 8 every 21 days until disease progression or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

1. Tumor Response Rate [Baseline up to 30 days of follow-up after 21 cycles of treatment]

   Participants with best overall response determined from complete response (CR) or partial response (PR) according to Response Criteria in Solid Tumors (RECIST) criteria. For CR or PR, best response must be confirmed. A second assessment performed at 28 days. Two determinations of CR before progression required for rate to=CR. Evaluations include: CR=Disappearance of lesions. PR=≥30% size decrease of lesions. Progressive Disease (PD)=≥20% size increase of lesions. Stable Disease (SD)=Not enough shrinkage for PR nor enough increase for PD. Overall Response Rate=PR+CR/Qualified Participants*100.

Secondary Outcome Measures

1. Duration of Response (DOR) [Time of response to progressive disease (up to 19 months)]

   DOR-RECIST criteria of (Complete Response [CR =Disappearance of lesions] or Partial Response [PR=≥30% size decrease of lesions]) is defined as time from the date when measurement criteria are met for CR or PR until the date of first observation of progressive disease (PD) or death from study disease. For participants who die from causes other than study disease and without PD, DOR will be censored at the date of death. For participants who have not died as of the data cut-off date who are without PD, DOR was censored at last contact date.

2. Time to Progressive Disease (PD) [Baseline to measured PD (up to 25.1 months)]

   Time to PD is defined as the time from the date of study enrollment to the first documented date of PD or death from study disease. For participants who die from causes other than study disease and without PD, time to PD was censored at the date of death. For participants not known to have died as of the data cut-off date and do not have PD, time to PD was censored at the last contact date. For participants who received subsequent chemotherapy (after discontinuation from the study chemotherapy) prior to disease progression, time to PD was censored at the date of subsequent chemotherapy.

3. Time To Treatment Failure (TTTF) [Baseline to end of treatment (up to 21.9 months)]

   TTTF is defined as the time from date of study enrollment to the first documented date of death, PD, or study treatment discontinuation due to adverse event (AE). For participants not known to have discontinued as of the data cut-off date, TTTF is censored at the last contact date. For participants who discontinued for reasons other than death, PD, or AE, TTTF is censored at the date of discontinuation.

4. Time to Response [Baseline to response (up to 7.8 months)]

   Time to response (Complete Response(CR) or Partial Response (PR) is defined as the time from the date of study enrollment to the first date when the measurement criteria are met for complete response or partial response (whichever status is recorded first). CR=Disappearance of target lesions lesions. PR=≥30% size decrease of lesions.

5. Number of Participants With Adverse Events (AE) [every cycle up to twenty-one 21-day cycles (plus 30 days of follow-up)]

   A listing of adverse events is presented in the Reported Adverse Event Module.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females with histologic or cytologic diagnosis of advanced breast cancer. Lesions should not be amenable to surgery or radiation of curative intent.

• Performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) performance status scale.

• One prior chemotherapy containing anthracyclines as (neo)adjuvant or palliative 1st-line treatment.

• One prior chemotherapy containing taxanes as (neo) adjuvant or palliative 1st-line treatment.

• Prior radiation therapy is allowed to less than 25% of the bone marrow. Participants must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed 30 days before study entry. Lesions that have been radiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.

• At least one uni-dimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Positron emission tomography [PET] scans and ultrasounds may not be used.

• Antitumoral hormonal treatment must be discontinued prior to enrollment.

• Estimated life expectancy of at least 3 months.

• Participant compliance and geographic proximity that allow adequate follow-up.

• Adequate organ function

• Female participants of childbearing potential must test negative for pregnancy within 7 days of enrollment based on a urine and/or serum pregnancy test and agree to use a reliable method of birth control during and for 6 months following the last dose of study drug.

• Participants must sign an informed consent document.

• Female participants must be at least 18 years of age.

Exclusion Criteria:

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.

• Have previously completed or withdrawn from this study or any other study investigating Pemetrexed, Gemcitabine, Carboplatin or Vinorelbine

• Have received more than one line of chemotherapy in Metastatic Breast Cancer. Participants having received more than one combination of anthracycline plus taxane.

• Are pregnant or breast-feeding.

• Have serious concomitant systemic disorders (e.g., active infection) that, in the opinion of the investigator, would compromise the safety of the participant or compromise the participant's ability to complete the study.

• Have a prior malignancy other than breast cancer, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence.

• Are unable to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period (8-day period for long-acting agents such as piroxicam), unless the Creatinine Clearance is greater than or equal to 80 ml/min.

• Have central nervous system (CNS) metastases.

• Have clinically relevant (by physical exam) third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study entry.

• Are unable or unwilling to take folic acid, vitamin B12 supplementation, or dexamethasone.

• Concurrent administration of any other antitumor therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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.	Guetersloh		Germany	33332
2	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.	Hamburg		Germany	22081
3	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.	Stuttgart		Germany	70190
4	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.	Bergamo		Italy	24128
5	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.	Bologna		Italy	40139
6	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.	Livorno		Italy	57128
7	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.	Meldola		Italy	47014
8	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.	Rome		Italy	00168
9	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.	San Giovanni Rotondo		Italy	71013
10	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.	Durban		South Africa	4067
11	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.	Morningside		South Africa	2199
12	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.	Pretoria		South Africa	0001
13	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.	Barcelona		Spain	08036
14	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.	Girona		Spain	17007
15	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.	La Coruña		Spain	15006
16	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.	Lleida		Spain	25198
17	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.	Madrid		Spain	28040
18	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.	Valencia		Spain	46010
19	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.	Zaragoza		Spain	50009
20	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.	Besevler/Ankara		Turkey	06500
21	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.	Bornova		Turkey	35100
22	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.	Kayseri		Turkey	38039

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00325234
• Other Study ID Numbers: 10826; H3E-EW-S098
• First Posted: May 12, 2006
• Last Update Posted: May 20, 2011
• Last Verified: Apr 1, 2011

• Additional relevant MeSH terms: Breast Neoplasms; Gemcitabine; Carboplatin; Pemetrexed; Vinorelbine

Study Results

Participant Flow

Arm/Group Title	Pemetrexed/Carboplatin	Gemcitabine/Vinorelbine
Arm/Group Description	Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC 5.0 mg*min/mL. The cycle of treatment was 21 days.	Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.
Period Title: Overall Study
STARTED	69	66
Received At Least 1 Dose of Study Drug	65	66
COMPLETED	0	0
NOT COMPLETED	69	66

Baseline Characteristics

Arm/Group Title	Pemetrexed/Carboplatin	Gemcitabine/Vinorelbine	Total
Arm/Group Description	Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC 5.0 mg*min/mL. The cycle of treatment was 21 days.	Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.	Total of all reporting groups
Overall Participants	69	66	135
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.9 (11.38)	52.3 (10.40)	52.1 (10.87)
Sex: Female, Male (Count of Participants)
Female	69 100%	66 100%	135 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	67 97.1%	61 92.4%	128 94.8%
African	1 1.4%	3 4.5%	4 3%
Hispanic	0 0%	1 1.5%	1 0.7%
East Asian	1 1.4%	0 0%	1 0.7%
West Asian	0 0%	1 1.5%	1 0.7%
Region of Enrollment (participants) [Number]
Spain	18 26.1%	18 27.3%	36 26.7%
Switzerland	5 7.2%	4 6.1%	9 6.7%
Israel	9 13%	9 13.6%	18 13.3%
Germany	9 13%	12 18.2%	21 15.6%
Italy	16 23.2%	14 21.2%	30 22.2%
Turkey	5 7.2%	3 4.5%	8 5.9%
South Africa	7 10.1%	6 9.1%	13 9.6%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
ECOG 0	39 56.5%	39 59.1%	78 57.8%
ECOG 1	28 40.6%	27 40.9%	55 40.7%
ECOG 2	2 2.9%	0 0%	2 1.5%
Hormonal Receptor Status (participants) [Number]
Estrogen and Progesterone Negative	19 27.5%	21 31.8%	40 29.6%
Estrogen and/or Progesterone Positive	49 71%	44 66.7%	93 68.9%
Unknown	1 1.4%	1 1.5%	2 1.5%
Human Epidermal Growth Factor Receptor 2 (HER-2/Neu) (participants) [Number]
Positive	12 17.4%	13 19.7%	25 18.5%
Negative	53 76.8%	49 74.2%	102 75.6%
Not Performed	0 0%	1 1.5%	1 0.7%
Unknown	4 5.8%	3 4.5%	7 5.2%
Tumor Differentiation Grade (participants) [Number]
Grade I	6 8.7%	3 4.5%	9 6.7%
Grade II	25 36.2%	27 40.9%	52 38.5%
Grade III	32 46.4%	30 45.5%	62 45.9%
Unknown	6 8.7%	6 9.1%	12 8.9%
Pathological Diagnosis (participants) [Number]
Carcinoma, Ductal, Breast	64 92.8%	54 81.8%	118 87.4%
Carcinoma, Lobular, Breast	4 5.8%	5 7.6%	9 6.7%
Carcinoma, Inflammatory, Breast	1 1.4%	3 4.5%	4 3%
Carcinoma, Mixed Cell, Breast	0 0%	1 1.5%	1 0.7%
Other	0 0%	3 4.5%	3 2.2%

Outcome Measures

1. Primary Outcome

Title	Tumor Response Rate
Description	Participants with best overall response determined from complete response (CR) or partial response (PR) according to Response Criteria in Solid Tumors (RECIST) criteria. For CR or PR, best response must be confirmed. A second assessment performed at 28 days. Two determinations of CR before progression required for rate to=CR. Evaluations include: CR=Disappearance of lesions. PR=≥30% size decrease of lesions. Progressive Disease (PD)=≥20% size increase of lesions. Stable Disease (SD)=Not enough shrinkage for PR nor enough increase for PD. Overall Response Rate=PR+CR/Qualified Participants*100.
Time Frame	Baseline up to 30 days of follow-up after 21 cycles of treatment

Outcome Measure Data

Analysis Population Description

All randomized patients who qualified for tumor response analysis by the following criteria: Females with histologic or cytologic diagnosis of advanced breast cancer previously treated with anthracyclines and taxanes. No concurrent antitumor therapy. Presence of measurable disease as defined by RECIST. Treatment with at least 1 dose of study drug.

Arm/Group Title	Pemetrexed/Carboplatin	Gemcitabine/Vinorelbine
Arm/Group Description	Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC 5.0. The cycle of treatment was 21 days.	Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 will be given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.
Measure Participants	64	61
Overall Response	26.6 38.6%	29.5 44.7%
Complete Response	0.0 0%	3.3 5%
Partial Response	26.6 38.6%	26.2 39.7%
Stable Disease	35.9 52%	34.4 52.1%
Progressive Disease	26.6 38.6%	27.9 42.3%
Unknown	10.9 15.8%	8.2 12.4%

2. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR-RECIST criteria of (Complete Response [CR =Disappearance of lesions] or Partial Response [PR=≥30% size decrease of lesions]) is defined as time from the date when measurement criteria are met for CR or PR until the date of first observation of progressive disease (PD) or death from study disease. For participants who die from causes other than study disease and without PD, DOR will be censored at the date of death. For participants who have not died as of the data cut-off date who are without PD, DOR was censored at last contact date.
Time Frame	Time of response to progressive disease (up to 19 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with CR or PR.

Arm/Group Title	Pemetrexed/Carboplatin	Gemcitabine/Vinorelbine
Arm/Group Description	Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC 5.0 mg*min/mL. The cycle of treatment was 21 days.	Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.
Measure Participants	17	19
Median (95% Confidence Interval) [Months]	7.7	7.5

3. Secondary Outcome

Title	Time to Progressive Disease (PD)
Description	Time to PD is defined as the time from the date of study enrollment to the first documented date of PD or death from study disease. For participants who die from causes other than study disease and without PD, time to PD was censored at the date of death. For participants not known to have died as of the data cut-off date and do not have PD, time to PD was censored at the last contact date. For participants who received subsequent chemotherapy (after discontinuation from the study chemotherapy) prior to disease progression, time to PD was censored at the date of subsequent chemotherapy.
Time Frame	Baseline to measured PD (up to 25.1 months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Pemetrexed/Carboplatin	Gemcitabine/Vinorelbine
Arm/Group Description	Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC 5.0 mg*min/mL. The cycle of treatment was 21 days.	Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.
Measure Participants	69	66
Median (95% Confidence Interval) [Months]	5.1	5.6

4. Secondary Outcome

Title	Time To Treatment Failure (TTTF)
Description	TTTF is defined as the time from date of study enrollment to the first documented date of death, PD, or study treatment discontinuation due to adverse event (AE). For participants not known to have discontinued as of the data cut-off date, TTTF is censored at the last contact date. For participants who discontinued for reasons other than death, PD, or AE, TTTF is censored at the date of discontinuation.
Time Frame	Baseline to end of treatment (up to 21.9 months)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Pemetrexed/Carboplatin	Gemcitabine/Vinorelbine
Arm/Group Description	Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC 5.0 mg*min/mL. The cycle of treatment was 21 days.	Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.
Measure Participants	69	66
Median (95% Confidence Interval) [Months]	4.8	5.1

5. Secondary Outcome

Title	Time to Response
Description	Time to response (Complete Response(CR) or Partial Response (PR) is defined as the time from the date of study enrollment to the first date when the measurement criteria are met for complete response or partial response (whichever status is recorded first). CR=Disappearance of target lesions lesions. PR=≥30% size decrease of lesions.
Time Frame	Baseline to response (up to 7.8 months)

Outcome Measure Data

Analysis Population Description

All randomized participants with CR or PR.

Arm/Group Title	Pemetrexed/Carboplatin	Gemcitabine/Vinorelbine
Arm/Group Description	Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC 5.0 mg*min/mL. The cycle of treatment was 21 days.	Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.
Measure Participants	17	19
Median (95% Confidence Interval) [Months]	1.8	1.8

6. Secondary Outcome

Title	Number of Participants With Adverse Events (AE)
Description	A listing of adverse events is presented in the Reported Adverse Event Module.
Time Frame	every cycle up to twenty-one 21-day cycles (plus 30 days of follow-up)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug.

Arm/Group Title	Pemetrexed/Carboplatin	Gemcitabine/Vinorelbine
Arm/Group Description	Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC 5.0 mg*min/mL. The cycle of treatment was 21 days.	Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.
Measure Participants	65	66
Adverse Events	64 92.8%	66 100%
Serious Adverse Events	18 26.1%	22 33.3%

Adverse Events

Arm/Group Title	Pemetrexed/Carboplatin		Gemcitabine/Vinorelbine
Arm/Group Description	Pemetrexed 600 mg/m^2 was administered intravenously over approximately 10 minutes on Day 1. Carboplatin was given over approximately 30 minutes on Day 1 beginning after the end of the Pemetrexed infusion, consistent with a target of AUC 5.0 mg*min/mL. The cycle of treatment was 21 days.		Vinorelbine 30 mg/m^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days.
All Cause Mortality
	Pemetrexed/Carboplatin		Gemcitabine/Vinorelbine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pemetrexed/Carboplatin		Gemcitabine/Vinorelbine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/65 (27.7%)		22/66 (33.3%)
Blood and lymphatic system disorders
Anaemia	5/65 (7.7%)	10	1/66 (1.5%)	1
Febrile neutropenia	1/65 (1.5%)	1	2/66 (3%)	2
Leukocytosis	0/65 (0%)	0	1/66 (1.5%)	1
Neutropenia	4/65 (6.2%)	6	2/66 (3%)	2
Thrombocytopenia	6/65 (9.2%)	10	0/66 (0%)	0
Cardiac disorders
Cardiac failure congestive	0/65 (0%)	0	1/66 (1.5%)	1
Gastrointestinal disorders
Epigastric discomfort	0/65 (0%)	0	1/66 (1.5%)	1
Nausea	1/65 (1.5%)	1	0/66 (0%)	0
Vomiting	3/65 (4.6%)	3	1/66 (1.5%)	1
General disorders
Condition aggravated	0/65 (0%)	0	1/66 (1.5%)	1
Medical device complication	0/65 (0%)	0	1/66 (1.5%)	1
Performance status decreased	1/65 (1.5%)	1	0/66 (0%)	0
Pyrexia	2/65 (3.1%)	2	3/66 (4.5%)	3
Hepatobiliary disorders
Hepatic failure	0/65 (0%)	0	1/66 (1.5%)	1
Jaundice	0/65 (0%)	0	1/66 (1.5%)	1
Infections and infestations
Breast cellulitis	0/65 (0%)	0	1/66 (1.5%)	1
Implant site infection	0/65 (0%)	0	1/66 (1.5%)	1
Pneumonia	2/65 (3.1%)	2	0/66 (0%)	0
Staphylococcal sepsis	0/65 (0%)	0	1/66 (1.5%)	1
Streptococcal infection	0/65 (0%)	0	1/66 (1.5%)	1
Wound infection	0/65 (0%)	0	1/66 (1.5%)	1
Injury, poisoning and procedural complications
Ankle fracture	0/65 (0%)	0	1/66 (1.5%)	1
Fall	0/65 (0%)	0	1/66 (1.5%)	1
Femur fracture	1/65 (1.5%)	1	0/66 (0%)	0
Joint dislocation	0/65 (0%)	0	1/66 (1.5%)	1
Investigations
Alanine aminotransferase increased	0/65 (0%)	0	1/66 (1.5%)	1
Aspartate aminotransferase increased	0/65 (0%)	0	1/66 (1.5%)	1
Blood glucose increased	0/65 (0%)	0	1/66 (1.5%)	1
International normalised ratio increased	0/65 (0%)	0	1/66 (1.5%)	1
Metabolism and nutrition disorders
Decreased appetite	1/65 (1.5%)	1	0/66 (0%)	0
Dehydration	1/65 (1.5%)	1	0/66 (0%)	0
Hypocalcaemia	1/65 (1.5%)	1	0/66 (0%)	0
Hypokalaemia	2/65 (3.1%)	2	0/66 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system	0/65 (0%)	0	1/66 (1.5%)	1
Nervous system disorders
Epilepsy	0/65 (0%)	0	1/66 (1.5%)	1
Transient ischaemic attack	1/65 (1.5%)	1	0/66 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/65 (1.5%)	1	0/66 (0%)	0
Dyspnoea exertional	0/65 (0%)	0	1/66 (1.5%)	1
Pharyngeal inflammation	0/65 (0%)	0	1/66 (1.5%)	1
Pleural effusion	1/65 (1.5%)	1	1/66 (1.5%)	1
Pulmonary embolism	1/65 (1.5%)	1	1/66 (1.5%)	1
Skin and subcutaneous tissue disorders
Rash	1/65 (1.5%)	1	0/66 (0%)	0
Vascular disorders
Deep vein thrombosis	0/65 (0%)	0	1/66 (1.5%)	1
Subclavian vein thrombosis	0/65 (0%)	0	1/66 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Pemetrexed/Carboplatin		Gemcitabine/Vinorelbine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/65 (98.5%)		66/66 (100%)
Blood and lymphatic system disorders
Anaemia	32/65 (49.2%)	46	28/66 (42.4%)	36
Leukopenia	28/65 (43.1%)	79	35/66 (53%)	84
Lymphopenia	10/65 (15.4%)	13	8/66 (12.1%)	15
Neutropenia	37/65 (56.9%)	120	51/66 (77.3%)	154
Thrombocytopenia	17/65 (26.2%)	34	11/66 (16.7%)	23
Cardiac disorders
Palpitations	1/65 (1.5%)	1	5/66 (7.6%)	5
Gastrointestinal disorders
Abdominal pain	3/65 (4.6%)	3	9/66 (13.6%)	12
Abdominal pain upper	5/65 (7.7%)	5	10/66 (15.2%)	13
Constipation	18/65 (27.7%)	24	26/66 (39.4%)	41
Diarrhoea	7/65 (10.8%)	7	12/66 (18.2%)	14
Dyspepsia	2/65 (3.1%)	3	6/66 (9.1%)	7
Dysphagia	4/65 (6.2%)	5	1/66 (1.5%)	1
Nausea	31/65 (47.7%)	48	23/66 (34.8%)	73
Stomatitis	7/65 (10.8%)	8	11/66 (16.7%)	12
Vomiting	15/65 (23.1%)	20	15/66 (22.7%)	19
General disorders
Asthenia	14/65 (21.5%)	23	13/66 (19.7%)	19
Fatigue	23/65 (35.4%)	38	26/66 (39.4%)	39
Oedema peripheral	6/65 (9.2%)	6	6/66 (9.1%)	7
Pyrexia	5/65 (7.7%)	6	21/66 (31.8%)	33
Investigations
Alanine aminotransferase increased	11/65 (16.9%)	16	21/66 (31.8%)	30
Aspartate aminotransferase increased	9/65 (13.8%)	14	17/66 (25.8%)	25
Blood alkaline phosphatase increased	7/65 (10.8%)	7	7/66 (10.6%)	8
Gamma-glutamyltransferase increased	4/65 (6.2%)	4	11/66 (16.7%)	16
Weight decreased	3/65 (4.6%)	3	8/66 (12.1%)	8
Metabolism and nutrition disorders
Decreased appetite	8/65 (12.3%)	10	12/66 (18.2%)	13
Hyperglycaemia	3/65 (4.6%)	6	5/66 (7.6%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	2/65 (3.1%)	2	5/66 (7.6%)	9
Back pain	5/65 (7.7%)	5	6/66 (9.1%)	17
Musculoskeletal pain	4/65 (6.2%)	4	6/66 (9.1%)	8
Pain in extremity	0/65 (0%)	0	5/66 (7.6%)	6
Nervous system disorders
Dizziness	5/65 (7.7%)	7	4/66 (6.1%)	4
Dysgeusia	3/65 (4.6%)	3	4/66 (6.1%)	4
Headache	7/65 (10.8%)	10	11/66 (16.7%)	16
Peripheral sensory neuropathy	3/65 (4.6%)	3	9/66 (13.6%)	14
Psychiatric disorders
Anxiety	1/65 (1.5%)	1	6/66 (9.1%)	6
Insomnia	6/65 (9.2%)	6	3/66 (4.5%)	3
Respiratory, thoracic and mediastinal disorders
Cough	5/65 (7.7%)	5	9/66 (13.6%)	11
Dyspnoea	4/65 (6.2%)	4	6/66 (9.1%)	7
Epistaxis	5/65 (7.7%)	6	2/66 (3%)	2
Skin and subcutaneous tissue disorders
Alopecia	8/65 (12.3%)	8	16/66 (24.2%)	16
Pruritus	6/65 (9.2%)	11	7/66 (10.6%)	7
Rash	4/65 (6.2%)	4	9/66 (13.6%)	10
Vascular disorders
Phlebitis	0/65 (0%)	0	6/66 (9.1%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.