Pemetrexed and Gemcitabine in Patients With Advanced Non-Small Cell Lung Cancer

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00193414
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 72
• Location: 1
• Arm: 1
• Duration (Months): 51
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

This study is designed to study the role of an active and well-tolerated non-platinum agent, gemcitabine, in a combination regimen with pemetrexed in the first-line treatment of advanced NSCLC. This study will serve to define the role of next generation agents in a new combination regimen in the treatment of advanced NSCLC. This combination regimen may ultimately be important in further expanding treatment options for patients while improving survival, quality of life, and symptom control compared with platinum-based combination regimens - and with acceptable toxicity.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: Pemetrexed; Drug: Gemcitabine	Phase 2

Detailed Description

Upon determination of eligibility, patients will be receive:

• Pemetrexed + Gemcitabine

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of First-Line Therapy With Pemetrexed and Gemcitabine in Patients With Advanced Non-Small Cell Lung Cancer
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Chemotherapy-naïve patients with unresectable stage III/IV NSCLC received pemetrexed 500 mg/m2 IV and gemcitabine 1500 mg/m2 IV every 2 weeks for 8-12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy.	Drug: Pemetrexed; 500mg/m2 IV over 10 min, Day 1, prior to gemcitabine; Other Names: Alimta ; Drug: Gemcitabine; 1500mg/m2, 30min IV; Other Names: Gemzar

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [18 months]

   Overall response rate is the percentage of patients with complete response or partial response per RECIST v.1 Criteria. Complete response (CR) = Disappearance of all target lesions, disappearance of all nontarget lesions for at least 4 weeks. Partial Response (PR) = At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters.

Secondary Outcome Measures

1. Progression-free Survival (PFS) [18 months]

   PFS was defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death from any cause.

2. Overall Survival (OS) [18 months]

   OS was measured from the date of study entry until the date of death.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

To be included in this study, you must meet the following criteria:

• Histologically confirmed non-small cell bronchogenic carcinoma

• Newly diagnosed or recurrent unresectable stage III or stage IV disease

• No mixed tumors with small cell anaplastic elements

• Measurable disease

• Must not have received any prior antineoplastic chemotherapy for lung cancer

• Age > 18 years

• Able to perform activities of daily living with little or no assistance

• Adequate bone marrow, liver and kidney

• Understand the nature of this study and give written informed consent.

Exclusion Criteria:

You cannot participate in this study if any of the following apply to you:

• Female patients who are pregnant or are lactating

• History of serious cardiovascular disease within the previous six months

• Serious active infection at the time of treatment

• Other serious underlying medical condition

Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tennessee Oncology	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Eli Lilly and Company

Investigators

• Principal Investigator: David R. Spigel, MD, SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Published article in the Journal of Thoracic Oncology

Publications

None provided.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00193414
• Other Study ID Numbers: SCRI LUN 91; H3E-US-X011
• First Posted: Sep 19, 2005
• Last Update Posted: Mar 3, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Lung Neoplasms; Gemcitabine; Pemetrexed

Study Results

Participant Flow

Arm/Group Title	Intervention
Arm/Group Description	Chemotherapy-naïve patients with unresectable stage III/IV NSCLC received pemetrexed 500 mg/m2 IV and gemcitabine 1500 mg/m2 IV every 2 weeks for 8-12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy.
Period Title: Overall Study
STARTED	72
COMPLETED	14
NOT COMPLETED	58

Baseline Characteristics

Arm/Group Title	Intervention
Arm/Group Description	Chemotherapy-naïve patients with unresectable stage III/IV NSCLC received pemetrexed 500 mg/m2 IV and gemcitabine 1500 mg/m2 IV every 2 weeks for 8-12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy.
Overall Participants	72
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	29 40.3%
>=65 years	43 59.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (8.7)
Sex: Female, Male (Count of Participants)
Female	25 34.7%
Male	47 65.3%
Region of Enrollment (participants) [Number]
United States	72 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	Overall response rate is the percentage of patients with complete response or partial response per RECIST v.1 Criteria. Complete response (CR) = Disappearance of all target lesions, disappearance of all nontarget lesions for at least 4 weeks. Partial Response (PR) = At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients were assessed for response.

Arm/Group Title	Intervention
Arm/Group Description	Chemotherapy-naïve patients with unresectable stage III/IV NSCLC received pemetrexed 500 mg/m2 IV and gemcitabine 1500 mg/m2 IV every 2 weeks for 8-12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy.
Measure Participants	72
Number (95% Confidence Interval) [Percentage of participants]	26 36.1%

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS was defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death from any cause.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients were assessed for PFS.

Arm/Group Title	Intervention
Arm/Group Description	Chemotherapy-naïve patients with unresectable stage III/IV NSCLC received pemetrexed 500 mg/m2 IV and gemcitabine 1500 mg/m2 IV every 2 weeks for 8-12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy.
Measure Participants	72
Median (95% Confidence Interval) [Months]	6.2

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was measured from the date of study entry until the date of death.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients were assessed for OS.

Arm/Group Title	Intervention
Arm/Group Description	Chemotherapy-naïve patients with unresectable stage III/IV NSCLC received pemetrexed 500 mg/m2 IV and gemcitabine 1500 mg/m2 IV every 2 weeks for 8-12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy.
Measure Participants	72
Median (95% Confidence Interval) [Months]	8.5

Adverse Events

Arm/Group Title	Intervention
Arm/Group Description	Chemotherapy-naïve patients with unresectable stage III/IV NSCLC received pemetrexed 500 mg/m2 IV and gemcitabine 1500 mg/m2 IV every 2 weeks for 8-12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy.
All Cause Mortality
	Intervention
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Intervention
	Affected / at Risk (%)	# Events
Total	39/72 (54.2%)
Blood and lymphatic system disorders
Hemoglobin	2/72 (2.8%)
Hemorrhage, GI	1/72 (1.4%)
Leukocytes	1/72 (1.4%)
Pancytopenia (NOS)	1/72 (1.4%)
Cardiac disorders
Cardiac General - Other (Congestive Heart Failure)	1/72 (1.4%)
Cardiac ischemia/infarction	1/72 (1.4%)
Supraventricular and nodal arrhythmia - Atrial Arrhythmia (NOS)	1/72 (1.4%)
Supraventricular and nodal arrhythmia - Atrial Fibrillation	4/72 (5.6%)
Supraventricular and nodal arrhythmia - Atrial Flutter	1/72 (1.4%)
Supraventricular and nodal arrhythmia - Supraventricular tachycardia	1/72 (1.4%)
Endocrine disorders
Pancreatic endocrine: glucose intolerance	1/72 (1.4%)
Gastrointestinal disorders
Constipation	1/72 (1.4%)
Dysphagia	1/72 (1.4%)
Pain - Gastrointestinal	1/72 (1.4%)
General disorders
Death not associated with CTCAE term - Disease Progression NOS	17/72 (23.6%)
Fatigue	1/72 (1.4%)
Fever	1/72 (1.4%)
Hypoxemia	3/72 (4.2%)
Pain - NOS	1/72 (1.4%)
Infections and infestations
Febrile Neutropenia	3/72 (4.2%)
Infection - Other (Cellulitis)	3/72 (4.2%)
Infection - Other (Pneumonia)	8/72 (11.1%)
Metabolism and nutrition disorders
Hypercalcemia	1/72 (1.4%)
Hypoglycemia	1/72 (1.4%)
Musculoskeletal and connective tissue disorders
Fracture (Limb)	1/72 (1.4%)
Nervous system disorders
Altered Mental Status	1/72 (1.4%)
CNS cerebrovascular ischemia	3/72 (4.2%)
Neurology - Other (Spinal Cord Compression)	1/72 (1.4%)
Seizure	1/72 (1.4%)
Renal and urinary disorders
Renal Failure	1/72 (1.4%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	1/72 (1.4%)
Dyspnea	2/72 (2.8%)
Pleural effusion	2/72 (2.8%)
Pulmonary/Upper Respiratory - Other (Post obstructive lung process)	1/72 (1.4%)
Vascular disorders
Thrombosis/thrombus/embolism	6/72 (8.3%)
Other (Not Including Serious) Adverse Events
	Intervention
	Affected / at Risk (%)	# Events
Total	72/72 (100%)
Blood and lymphatic system disorders
Edema	33/72 (45.8%)
Cardiac disorders
Cardiac Toxicity	7/72 (9.7%)
Hypotension	5/72 (6.9%)
Pulmonary symptoms	16/72 (22.2%)
Gastrointestinal disorders
Anorexia	31/72 (43.1%)
Diarrhea	14/72 (19.4%)
Mucositis	16/72 (22.2%)
Nausea	38/72 (52.8%)
Vomiting	17/72 (23.6%)
General disorders
Fatigue	72/72 (100%)
Fever	20/72 (27.8%)
Pain - NOS	32/72 (44.4%)
Infections and infestations
Febrile Neutropenia	8/72 (11.1%)
Infection (NOS)	33/72 (45.8%)
Musculoskeletal and connective tissue disorders
Pain - Joints	8/72 (11.1%)
Pain - muscles	8/72 (11.1%)
Nervous system disorders
Peripheral Neuropathy NOS	5/72 (6.9%)
Skin and subcutaneous tissue disorders
Alopecia	16/72 (22.2%)
Skin Toxicity	32/72 (44.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at the site.