A Study of Home Administration of Pemetrexed as Maintenance Treatment for Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC)

Non-Small Cell Lung Cancer Metastatic Clinical Trial

Official title:

Home Delivery of Pemetrexed as Maintenance Treatment in Patients Who Have Not Progressed After Induction Therapy for Advanced Nonsquamous Nonsmall Cell Lung Cancer: A Feasibility Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01473563
• Other study ID #: 14079
• Secondary ID: H3E-EW-S133
• Status: Completed
• Phase: Phase 2
• First received: November 2, 2011
• Last updated: October 3, 2014
• Start date: December 2011
• Est. completion date: September 2013

Study information

• Verified date: October 2014
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The main purpose for this study is to answer the following research questions:

• Can pemetrexed be administered safely at the participant's home, using the same treatment procedure as in a hospital setting?

• Will the participant be satisfied with home care?

• How might this impact the participant's quality of life?

• What are the required medical resources needed to give pemetrexed in a home setting?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have a histological or cytological diagnosis of NSCLC defined as nonsquamous cell histology. Squamous cell and/or small cell histology is not permitted. Mixed NSCLC tumors will be categorized by the predominant cell type. NSCLC tumors that are not otherwise specified with regard to histology or cannot be subclassified as squamous, adenocarcinoma, or large cell histology will be categorized as nonsquamous

• Have Stage IIIB (not amenable to curative treatment) or Stage IV NSCLC prior to induction therapy as defined by the American Joint Committee on Cancer (AJCC) Staging Criteria for Lung Cancer

• Have completed 4 induction cycles of platinum-based doublet therapy (type at the discretion of the physician) for treatment of their advanced disease.

• Have not progressed after 4 cycles of induction therapy. Documented radiographic evidence of a tumor response must occur at the end of Cycle 4 of induction therapy within 3 weeks before receiving the first cycle of study drug [see Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.1]

• Receive on-study treatment no earlier than 21 days and no later than 42 days from Cycle 4 Day 1 of induction therapy

• Have a Performance Status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

• Meet the following guidelines if the participant has received prior radiation therapy:

• Previous radiation therapy is allowed to <25% of the bone marrow, but should have been limited and must not have included whole pelvis radiation

• Participants must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia)

• Participants who received palliative chest (in other words, thoracic skeleton including dorsal spine) or palliative extrathoracic radiotherapy to preexisting lesions are allowed to be enrolled in this trial

• Have adequate organ function, including:

• Adequate bone marrow reserve: absolute neutrophil count (ANC) (segmented and bands) >=1.5x109/Liter (L), platelets >=100x109/L, and hemoglobin >=9 grams per deciliter (g/dL)

• Hepatic: bilirubin <=1.5 x upper limit of normal (ULN) and alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) <=3.0 x ULN (ALP, AST, and ALT <=5.0 x ULN are acceptable if the liver has tumor involvement

• Renal: calculated creatinine clearance (CrCl) >=45 milliliters per minute (mL/min) based on the original weight-based Cockcroft and Gault formula

• Are willing to comply with the following contraceptive criteria:

• Females must be surgically sterile, postmenopausal or must have a negative serum or urine pregnancy test within 7 days prior to the first dose of study drug

• Males and females with reproductive potential: Must agree to use a reliable method of birth control during the study and for 6 months following the last dose of study drug

• Have an estimated life expectancy of at least 12 weeks

• Have given written informed consent/assent prior to any study-specific procedures

• Are willing to comply with home delivery administration and have family or close environment support willing to comply with home delivery administration

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or no approved use of a drug or device (other than pemetrexed used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

• Have previously completed or withdrawn from this study

• Have a serious concomitant systemic disorder (for example, active infection including human immunodeficiency virus)

• Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV

• Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants for at least 1 week before starting study treatment and their disease is asymptomatic and radiographically stable

• Are receiving concurrent administration of any other antitumor therapy

• Have a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results

• Are unable to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than aspirin dose =1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam)

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

• Are unable or unwilling to take corticosteroids

• Are pregnant or lactating

• Have received a recent (within 30 days of enrollment) or are receiving concurrent yellow fever vaccination

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer Metastatic
• Non-Small Cell Lung Cancer Stage IIIB
• Nonsquamous Non-Small Cell Neoplasm of Lung

Intervention

Drug:
• Pemetrexed
Administered intravenously

Locations

Country	Name	City	State
Sweden	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.	Linkoping
Sweden	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.	Solna
United Kingdom	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.	Aberdeen	Scotland
United Kingdom	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.	Birmingham
United Kingdom	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.	Huddersfield	West Yorkshire
United Kingdom	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.	London	Greater London
United Kingdom	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.	Maidstone	Kent
United Kingdom	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.	Manchester
United Kingdom	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.	Nottingham	Nottinghamshire

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Died	The number of participants who had at least 1 TEAE or serious TEAE (regardless of causality) is reported along with the number of participants who died (due to any cause) while on therapy or during treatment discontinuation follow-up (up to 6 months). TEAEs started on or after the date and time of first dose of study drug, or started prior to study drug but worsened after study drug started. Clinically significant events were defined as SAEs and other non-serious adverse events (AEs). A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events module.	First dose of study drug (Cycle 1, Day 1) through study completion [up to Cycle 19 (21 days/cycle) or treatment discontinuation, plus up to 6 months post treatment discontinuation]	Yes
Primary	Percentage of Participants Who Adhered to Treatment Administration at Home	Participants were considered adherent from the time of the first dose in Cycle 1 (hospital administration) until either the last day of the cycle when the participant reverted to pemetrexed hospital administration or the last day of the cycle when the participant discontinued study treatment or the study for reasons related to the home setting. The percentage of participants who adhered to treatment administration at home was estimated by a Kaplan-Meier survival analyses approach. Participants who died or discontinued the study and treatment without reverting to hospital administration were censored at the time of discontinuation.	Cycle 1, Day 1 through Cycle 19, Day 1 and Cycle 19, Day 1 (21 days/cycle)	No
Secondary	Change From Baseline in the European Quality of Life Instrument (EQ-5D) Visual Analogue Scale (VAS)	The EQ-5D scale was used to provide an estimate of the health state utility in this population. The EQ-5D scale includes a 5-dimensional descriptive system that measures each of the health state attributes: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression according to a 3-point scale (no problem, some problems, and major problems) and a VAS that allows participants to rate their present health condition from 0 (worst imaginable health state) to 100 (best imaginable health state). The change from baseline in EQ-5D VAS is reported.	Baseline, Day 1 of Cycles 2 and 4 (21 days/cycle) and 30 days post treatment discontinuation	No
Secondary	Change From Baseline in the EQ-5D Index Score	The EQ-5D scale was used to provide an estimate of the health state utility in this population. The EQ-5D scale includes a 5-dimensional descriptive system that measures each of the health state attributes: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression according to a 3-point scale (no problem, some problems, and major problems) and a VAS that allows participants to rate their present health condition from 0 (worst imaginable health state) to 100 (best imaginable health state). The change from baseline EQ-5D Index score is reported and the EQ-5D Index score was calculated by converting health state scores into a weighted health state index according to a United Kingdom population-based algorithm. The possible values for the EQ-5D Index score range from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension), on a scale where 1 represents the best possible health state.	Baseline, Day 1 of Cycles 2 and 4 (21 days/cycle) and 30 days post treatment discontinuation	No
Secondary	Maximum Improvement Over Baseline in Individual Lung Cancer Symptoms Scale (LCSS) Item Scores	LCSS is a 9-item questionnaire; 6 items are symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items describe overall symptomatic distress, interference with activity level, and overall quality of life during the past 24 hours. Participant responses were measured using a VAS with 100-millimeter (mm) lines. Scores ranged from 0 mm (no symptoms and no impact on activities, quality of life) to 100 mm (symptoms as bad as they could be, impacting activities and quality of life).	Baseline, Day 1 of each cycle (up to Cycle 19, 21 days/cycle), and 30 days post treatment discontinuation	No
Secondary	Participant Satisfaction: Chemotherapy at Hospital	Participants were asked to evaluate their hospital experiences in this study by answering 4 questions (Q). Q1: "What do you consider advantages of having chemotherapy at the hospital? Choose all that apply." Choices included: "Support from other patients", "Access to other medical specialists", "Access to more technical services", "Safer in case something goes wrong", and "Other". Q2: "What do you consider disadvantages of having chemotherapy at the hospital? Choose all that apply." Choices included: "Need to travel", "Having to wait for treatment", "Not having a personalized treatment", "Lack of privacy on the ward", and "Other". Q3: "How would you rate your overall satisfaction with chemotherapy at the hospital?" and Q4: "How would you rate your overall satisfaction with the nursing staff during chemotherapy at the hospital?" Choices for Q3 and Q4 included: "Very dissatisfied", "Somewhat dissatisfied", "Neither satisfied nor dissatisfied", "Somewhat satisfied", or "Very satisfied".	The first evaluation completed at either Cycle 4, Day 1 (21 days/cycle) or 30 days post treatment discontinuation	No
Secondary	Participant Satisfaction: Chemotherapy at Home	Participants were asked to evaluate their home treatment experiences in this study by answering 4 questions (Q). Q5: "What do you do consider advantages of having chemotherapy at home? Choose all that apply." Choices included: "No need to travel", "Not having to wait for treatment", "Personalized service", "More privacy", and "Other". Q6:"What do you consider disadvantages of having chemotherapy at home? Choose all that apply." Choices included: "Lack of other patients' support", "Extra burden for family/friends", "Safety concerns", "Need to rely on 1 medical specialist", and "Other". Q7: "How would you rate your overall satisfaction with chemotherapy at home?" Choices included: "Very dissatisfied", "Somewhat dissatisfied", "Neither satisfied nor dissatisfied", "Somewhat satisfied", or "Very satisfied".	The first evaluation completed at either Cycle 4, Day 1 (21 days/cycle) or 30 days post treatment discontinuation	No
Secondary	Participant Satisfaction: Regarding the Study Nurse	Participants were asked 7 questions (Q) about their study nurse for home treatment. Q8: "Was the nurse an easy person to talk to?", Q9: "When the nurse came, did you feel he/she had enough time to do the required things?", Q10: "Do you think the nurse had time to discuss things with you?", Q11: "Did you feel that the nurse knew enough about you and your illness?" Choices for Q8 through Q11 included: "Yes" or "No". Q12: "Were you able to get all the information you wanted about your illness or treatment?" Choices included: "Yes", "No", or "Uncertain". Q13: "Would you say that the nurse gave…" Choices included: "a lot of reassurance and support", "some reassurance and support", or "hardly any reassurance and support". Q14: "How would you rate your overall satisfaction with the nursing staff during chemotherapy at home?" Choices included: "Very dissatisfied", "Somewhat dissatisfied", "Neither satisfied nor dissatisfied", "Somewhat satisfied", or "Very satisfied".	The first evaluation completed at either Cycle 4, Day 1 (21 days/cycle) or 30 days post treatment discontinuation	No
Secondary	Participant Satisfaction: Preferences Regarding Home and/or Hospital Treatment	Participants were asked to evaluate their preferences regarding home and/or hospital treatment delivery in this study by answering 2 questions (Q). Q15: "Do you prefer having your chemotherapy at home or at the hospital, or are you indifferent?" Choices included: "Home", "Hospital", or "Indifferent". Q16: "Would you recommend having chemotherapy at home to someone else in your same situation?" Choices included: "Yes", "No", or "Not sure".	The first evaluation completed at either Cycle 4, Day 1 (21 days/cycle) or 30 days post treatment discontinuation	No
Secondary	Physician Satisfaction: Distant Management of Participant	The physician was asked, "How would you rate your overall satisfaction with the distant management of the participant during chemotherapy at home?" Choices included: "Very dissatisfied", "Somewhat dissatisfied", "Neither satisfied nor dissatisfied", "Somewhat satisfied", or "Very satisfied".	30 days post treatment discontinuation	No
Secondary	Resource Utilization: Number of Participants With an Unplanned Use of Healthcare Resources	The number of participants who had at least 1 unplanned use of health care resources [accident and emergency department (dept.), specialists [oncologist, pulmonologist, etcetera (etc.)], general practitioner (GP) or family doctor, or diagnostic procedures] during the study is reported.	Cycle 1, Day 1 through last day of cycle when participant reverted to hospital administration or discontinued (up to Cycle 19, 21 days/cycle)	No
Secondary	Resource Utilization: Unplanned Health Care Visits, Consultations, and Diagnostic Services	The unplanned use of any 1 of the following 4 resources is reported, as well as the unplanned use of each resource: accident and emergency dept., specialists (oncologist, pulmonologist etc.), GP or family doctor, and diagnostic procedures. Results are reported as the number of participants with an unplanned resource use (visit) for a specified number of times.	Cycle 1, Day 1 through last day of cycle when participant reverted to hospital administration or discontinued (up to Cycle 19, 21 days/cycle)	No
Secondary	Resource Utilization: Duration of Health Care Visits	The duration of the health care visit in the home setting is reported. The visit started when the nurse arrived and included the entire treatment process. The visit ended when the nurse left the home setting. Due to the limited number of participants with evaluable data, results are reported for Cycles 2 through 4.	Cycle 2, Day 1 through last day of cycle when participant reverted to hospital administration or discontinued (up to Cycle 4, 21 days/cycle)	No
Secondary	Resource Utilization: Distances Traveled	The distance traveled is reported by region (Great Britain and Sweden) and includes the distance traveled by the participant from his/her home to the hospital (Cycle 1) and other cycles where the homecare nurse traveled from the hospital to the participant's home. Due to the limited number of participants with evaluable data, results are reported for Cycles 1 through 4.	Cycle 1, Day 1 through last day of cycle when participant reverted to hospital administration or discontinued (up to Cycle 4, 21 days/cycle)	No
Secondary	Overall Survival (OS) at 6 Months	The percentage of participants who were alive at Month 6 was calculated as a cumulative percentage by Kaplan-Meier survival analyses approach. For participants not known to have died as of the cut-off date, OS was censored as the last contact date (known alive).	Cycle 1, Day 1 to the date of death from any cause (up to Month 6)	No
Secondary	Time to Treatment Failure (TTF)	The time from the date of the first dose of study treatment (Cycle 1, Day 1) to the date of death from any cause, PD (clinical and objective), or discontinuation of pemetrexed due to toxicity. Response was defined using RECIST, v1.1 criteria. PD was defined as having at least a 20% increase in the sum of the longest diameter of target lesions and at a minimum 5 mm increase above nadir. TTF was censored at the date of the last visit for participants who did not discontinue pemetrexed, who were still alive, and who had not progressed.	Cycle 1, Day 1 to first event (up to Cycle 19, 21 days/cycle)	Yes