Single Agent Alimta in Poor Performance Status in Non-small Cell Lung Cancer

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00508144
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 64
• Location: 1
• Arm: 1
• Duration (Months): 123
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn how effective the drug pemetrexed (ALIMTA®) is in treating advanced NSCLC in patients with poor performance status (PS) (inability to perform every day activities without difficulty).

Objectives:

Primary Objectives:

• PS = 2 cohort: Response

• PS = 3 cohort: Descriptive

Secondary Objectives:

• Tolerability of single agent pemetrexed (Alimta®) in PS = 3 NSCLC patients

• Improved symptoms (both cohorts)

• Molecular Correlative studies (both cohorts)

• Overall survival

• Time to progression

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: Alimta	Phase 2

Detailed Description

Pemetrexed is designed to block enzymes in the body that are important for tumor growth. Pemetrexed is commercially approved for the treatment of NSCLC but not for poor performance status patients.

If participants are found to be eligible to take part in this study, they will receive pemetrexed once every 3 weeks through a needle in their vein over about 10 minutes. Every 3 weeks is considered 1 treatment cycle. Once the treatment has started, they will return to the clinic before every treatment cycle. At these visits, they will have a physical exam, a performance status evaluation, and routine blood (about 3-4 teaspoons) and urine tests. They will have a chest x-ray and will be asked to complete a questionnaire about how you are feeling. they will also have a CT or MRI scan after Cycle 1 and every odd cycle from then on.

They are required to take folic acid by mouth every day for 5 days before the first dose of pemetrexed and continuing until 3 weeks after your last dose of pemetrexed. They will also receive an injection of vitamin B12 into your muscle before first dose of pemetrexed. The vitamin B12 injection will be repeated every 9 weeks until 3 weeks after their last dose of pemetrexed.

They will also to take a few low-dose steroid (dexamethasone) tablets twice a day before treatment, the day of treatment, and the day after each treatment. These will be taken to decrease the risk of rash and nausea caused by pemetrexed.

They may continue treatment with pemetrexed until your tumor grows or an unacceptable side effect occurs. They will be evaluated for symptoms 1-2 times per week while you are receiving treatment and then 2 weeks after stopping study treatment until 6 months after stopping treatment.

When they stop treatment on this study, they will have a physical exam, routine blood (3-4 teaspoons) and urine tests, and a chest x-ray. The study doctor may ask them to visit University of Texas MD Anderson Cancer Center or be contacted by phone for follow-up on how they are doing.

This is an investigational study. The FDA has approved pemetrexed for the treatment of advanced NSCLC after earlier treatment with chemotherapy, and for the treatment for malignant mesothelioma in combination with cisplatin. About 70 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single Agent Alimta in Poor Performance Status in Patients With Non-Small Cell Lung Cancer (NSCLC)
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alimta Alimta 500 mg/m^2 by vein Once Over 10 Minutes Every 3 Weeks.	Drug: Alimta; 500 mg/m^2 by vein Once Over 10 Minutes Every 3 Weeks; Other Names: Pemetrexed LY231514 MTA Multitargeted Antifolate NSC-698037

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (OR) Where OR=CR+PR: Number of Participants With Responses of Complete Response (CR) and Partial Response (PR) [Evaluated with 3 week treatment cycles, up to 4 cycles or 12 weeks]

   Complete Response (CR): Complete disappearance of all measurable & non-measurable disease; No new lesions; No disease related symptoms; Normalization of markers & other abnormal lab values. Partial Response (PR): Applies only to those with at least one measurable lesion. >/= 30% decrease under baseline of sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions assessed using same techniques as baseline. Progression: 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using same techniques as baseline. Unequivocal progression of non-measurable disease in opinion of treating physician. Evaluated for symptoms 1-2 times per week while receiving treatment then 2 weeks after stopping study treatment (expected 4 cycles).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Histologically or cytologically proven Stage IIIB (T4 lesion due to malignant pleural or pericardial effusion) or Stage IV. Clinically significant pleural or peritoneal effusions should be drained prior to dosing.

2. Zubrod PS 2 or PS 3

3. Patients with asymptomatic brain metastases and no requirement for corticosteroids or anticonvulsants are eligible for this clinical trial.

4. Measurable OR non-measurable disease documented by CT or MRI.

5. Patients may have had </=1 prior chemotherapy regimens but multiple prior biologic regimens. At least 4 weeks need to have elapsed since last chemotherapy or biologic therapy administration.

6. Prior radiation therapy is permitted; however, at least two weeks must have elapsed since the completion of prior radiation therapy and patients must have recovered from all associated toxicities at the time of registration. Measurable or non-measurable disease must be outside the previous radiation field OR patients with visible progression or new lesions within the radiation field are eligible.

7. At least two weeks must have elapsed since surgery and patients must have recovered from all associated toxicities at the time of registration.

8. Creatinine clearance >/= 45 cc/min measured or calculated using the following formula: Calculated Creatinine Clearance = (140 - age) X WT (kg) X (0.85 if female)/72 X creatinine (mg/dl) Calculated Creatinine Clearance = (140 - age) X WT (kg) X (1.00 if male)/72 X creatinine (mg/dl)

9. Absolute neutrophil count (ANC) >/= 1,500/µl

10. Platelet >/= 100,000/µl

11. ALT/AST: </=3.0 x upper limit of normal (ULN) except in known hepatic metastasis wherein may be </= 5 x ULN

12. Bilirubin: </=1.5 x ULN

13. Hemoglobin: >/=9.0 x 10^9/L

14. Patient must not be pregnant or breastfeeding. Patients of childbearing potential agree to practice an effective contraceptive method for the duration of the study.

15. Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

16. Men and women, aged >/=18 years.

Exclusion Criteria:

1. Prior treatment with pemetrexed therapy.

2. Patients planning to receive any other concomitant anticancer treatment including chemotherapy, radiation therapy, biologic agents or any other investigational drugs.

3. Women who are pregnant or breastfeeding may not participate in this trial. All women of childbearing potential must have a negative pregnancy test within 24 hours prior to enrolling in the study.

4. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period (8-day period for long-acting agents, such as piroxicam).

5. Inability and unwillingness to take folic acid or vitamin B12 supplementation.

6. Inability to take corticosteroids.

7. Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission or other cancer from which the patient has been disease-free for >/= 5 years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Eli Lilly and Company

Investigators

• Principal Investigator: Ralph Zinner, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00508144
• Other Study ID Numbers: 2004-0957; NCI-2012-01581
• First Posted: Jul 27, 2007
• Last Update Posted: Feb 13, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by M.D. Anderson Cancer Center: Non-Small Cell Lung Cancer; Lung Cancer; NSCLC; Malignant pleural effusion; Pericardial effusion; Pemetrexed; Alimta; LY231514; Poor Performance Status; Asymptomatic Brain Metastases
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pemetrexed

Study Results

Participant Flow

Recruitment Details	Recruitment Period: September 1, 2005 to June 30, 2011. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment Detail	Of the 64 participants registered, fifty-eight (58) were eligible, four (4) were invaluable, and six (6) were not eligible to participate in this trial.

Arm/Group Title	Alimta
Arm/Group Description	Alimta 500 mg/m^2 by vein once over 10 minutes every 3 weeks.
Period Title: Overall Study
STARTED	64
COMPLETED	53
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Alimta
Arm/Group Description	Alimta 500 mg/m^2 by vein once over 10 minutes every 3 weeks.
Overall Participants	64
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68
Gender (Count of Participants)
Female	24 37.5%
Male	40 62.5%
Region of Enrollment (participants) [Number]
United States	64 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (OR) Where OR=CR+PR: Number of Participants With Responses of Complete Response (CR) and Partial Response (PR)
Description	Complete Response (CR): Complete disappearance of all measurable & non-measurable disease; No new lesions; No disease related symptoms; Normalization of markers & other abnormal lab values. Partial Response (PR): Applies only to those with at least one measurable lesion. >/= 30% decrease under baseline of sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions assessed using same techniques as baseline. Progression: 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using same techniques as baseline. Unequivocal progression of non-measurable disease in opinion of treating physician. Evaluated for symptoms 1-2 times per week while receiving treatment then 2 weeks after stopping study treatment (expected 4 cycles).
Time Frame	Evaluated with 3 week treatment cycles, up to 4 cycles or 12 weeks

Outcome Measure Data

Analysis Population Description

Of 58 eligible participants, only 54 treated were available for response and five (5) experienced an early death, five (5) were later deemed inevaluable, and two had an indeterminate response.

Arm/Group Title	Alimta
Arm/Group Description	Alimta 500 mg/m^2 by vein once over 10 minutes every 3 weeks.
Measure Participants	42
Count of Participants [Participants]	3 4.7%

Adverse Events

Time Frame	Adverse event data collected for three-week treatment cycle, up to four cycles or 12 weeks.
Arm/Group Title	Alimta
Arm/Group Description	Alimta 500 mg/m^2 by vein once over 10 minutes every 3 weeks.
All Cause Mortality
	Alimta
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Alimta
	Affected / at Risk (%)	# Events
Total	32/58 (55.2%)
Blood and lymphatic system disorders
ANEMIA	6/58 (10.3%)	6
LEUKOCYTOSIS	1/58 (1.7%)	1
LEUKOPENIA	1/58 (1.7%)	1
NEUTROPENIC FEVER	3/58 (5.2%)	3
Cardiac disorders
ATRIAL FIBRILLATION	1/58 (1.7%)	1
CARDIOPULMONARY ARREST	1/58 (1.7%)	1
NONSUSTAINED VENTRICULAR TACHYCARDIA	1/58 (1.7%)	1
SINUS TACHYCARDIA	1/58 (1.7%)	1
Gastrointestinal disorders
ISCHEMIC ILEITIS/COLITIS	1/58 (1.7%)	1
General disorders
Death	5/58 (8.6%)	5
Chest Pain	1/58 (1.7%)	1
Infections and infestations
SEPTIC SHOCK	1/58 (1.7%)	1
Injury, poisoning and procedural complications
LEFT FEMUR FRACTURE	1/58 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
BRONCHIECTASIS EXACERBATION	1/58 (1.7%)	1
BRONCHITIS	1/58 (1.7%)	1
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)	2/58 (3.4%)	2
DYSPNEA	3/58 (5.2%)	3
HEMOPTYSIS	3/58 (5.2%)	3
PNEUMONIA	8/58 (13.8%)	8
PULMONARY EMBOLISM	2/58 (3.4%)	2
RESPIRATORY FAILURE	1/58 (1.7%)	1
Skin and subcutaneous tissue disorders
CELLULITIS	2/58 (3.4%)	2
Vascular disorders
HYPOTENSION	2/58 (3.4%)	2
Other (Not Including Serious) Adverse Events
	Alimta
	Affected / at Risk (%)	# Events
Total	43/58 (74.1%)
Blood and lymphatic system disorders
ANEMIA	4/58 (6.9%)	4
FEBRILE NEUTROPENIA	1/58 (1.7%)	1
FEVER NEUTROPENIC	3/58 (5.2%)	3
Leukocytosis	2/58 (3.4%)	2
LYMPHOPENIA	2/58 (3.4%)	2
Cardiac disorders
ATRIAL FIBRILLATION	2/58 (3.4%)	2
CARDIOVASCULAR GENERAL	1/58 (1.7%)	1
SINUS TACHYCARDIA	1/58 (1.7%)	1
VENTRICULAR TACHYCARDIA	1/58 (1.7%)	1
Gastrointestinal disorders
CONSTIPATION	2/58 (3.4%)	2
DIARRHEA	1/58 (1.7%)	1
DRY MOUTH	2/58 (3.4%)	2
GASTROINTESTINAL DISORDERS (Belly pain)	1/58 (1.7%)	1
MUCOSITIS (CLINICAL)	1/58 (1.7%)	1
NAUSEA	9/58 (15.5%)	9
STOMATITIS	1/58 (1.7%)	1
VOMITING	1/58 (1.7%)	1
General disorders
CONSTITUTIONAL SYMPTOMS, FATIGUE	1/58 (1.7%)	1
EDEMA	2/58 (3.4%)	2
FATIGUE	10/58 (17.2%)	10
FEVER UNKNOWN ORIGIN	7/58 (12.1%)	7
FEVER WITHOUT NEUTROPENIA	2/58 (3.4%)	2
Infections and infestations
BRONCHITIS	3/58 (5.2%)	3
COLITIS	1/58 (1.7%)	1
INFECTION	3/58 (5.2%)	3
INFECTION (OTHER)	1/58 (1.7%)	1
INFECTION UNKNOWN	1/58 (1.7%)	1
Infection with Normal White Blood Count	2/58 (3.4%)	2
Infection with Normal Absolute Neutrophil Count (ANC)	5/58 (8.6%)	5
WOUND INFECTION	2/58 (3.4%)	2
Investigations
Alkaline phosphatase increased	1/58 (1.7%)	1
Alanine aminotransferase decreased	2/58 (3.4%)	2
Alanine aminotransferase increased	2/58 (3.4%)	2
Aspartate aminotransferase increased	5/58 (8.6%)	5
Blood bilirubin increased	1/58 (1.7%)	1
Creatinine increased	1/58 (1.7%)	1
Hemoglobin increased	16/58 (27.6%)	16
Neutrophil count decreased	3/58 (5.2%)	3
Platelet count decreased	5/58 (8.6%)	5
WEIGHT LOSS	3/58 (5.2%)	3
Metabolism and nutrition disorders
ANOREXIA	5/58 (8.6%)	5
DEHYDRATION	1/58 (1.7%)	1
GLUCOSE, SERUM-HIGH	1/58 (1.7%)	1
HYPERGLYCEMIA	2/58 (3.4%)	2
HYPERKALEMIA	2/58 (3.4%)	2
HYPERURICEMIA	1/58 (1.7%)	1
HYPOCALCEMIA	1/58 (1.7%)	1
HYPOGLYCEMIA	1/58 (1.7%)	1
HYPOKALEMIA	6/58 (10.3%)	6
HYPOMAGNESEMIA	1/58 (1.7%)	1
HYPONATREMIA	5/58 (8.6%)	5
HYPOPHOSPHATEMIA	1/58 (1.7%)	1
Nervous system disorders
DIZZINESS	2/58 (3.4%)	2
SENSORY ALTERATION	1/58 (1.7%)	1
Psychiatric disorders
INSOMNIA	1/58 (1.7%)	1
Renal and urinary disorders
RENAL/GENITOURINARY DISORDER	1/58 (1.7%)	1
URINARY RETENTION	1/58 (1.7%)	1
Reproductive system and breast disorders
CANDIDIASIS	1/58 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	3/58 (5.2%)	3
DYSPNEA	8/58 (13.8%)	8
HEMOPTYSIS	3/58 (5.2%)	3
HEMORRHAGE, PULMONARY	2/58 (3.4%)	2
PLEURAL EFFUSION	3/58 (5.2%)	3
PULMONARY (OTHER)	2/58 (3.4%)	2
PULMONARY EMBOLISM	1/58 (1.7%)	1
Skin and subcutaneous tissue disorders
DRY SKIN	2/58 (3.4%)	2
RASH/DESQUAMATION	3/58 (5.2%)	3
SWEATING	1/58 (1.7%)	1
Vascular disorders
HYPOTENSION	1/58 (1.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.