Lung Cancer, Non Small Cell Lung Carcinoma
Conditions
Keywords
Lung cancer
Brief summary
This open-label, multicenter, randomized, controlled, Phase II study is planned to answer questions about how the drug, matuzumab (EMD 72000), works and is part of an effort aimed to develop better treatment for advanced lung cancer by combining matuzumab, a monoclonal antibody, with a chemotherapy treatment, called pemetrexed.
Interventions
DRUGPemetrexed
Pemetrexed will be administered IV until PD or the occurrence of unacceptable toxicity.
DRUGMatuzumab
Matuzumab will be administered IV until PD or the occurrence of unacceptable toxicity.
Sponsors
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent provided prior to any screening procedure * Male or female, greater than (\>) 18 years of age * Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) * Demonstrated PD on or after first-line chemotherapy for Stage IIIB/IV disease. The first-line therapy must consist of platinum-based regimens in combination with taxanes, gemcitabine or vinorelbine. Stage IIIB/IV participants must have measurable disease (tumor) without clinically significant pleural effusion unless the pleural effusion can be effectively drained prior to admission into the study * A chemotherapy-free interval of at least 3 weeks between the end of first-line chemotherapy and start of study treatment * At least 1 measurable lesion according to the modified World Health Organization (WHO) criteria * Archived tissue or cytologic sample available for the determination of epidermal growth factor receptor (EGFR) expression * Eastern cooperative oncology group (ECOG) performance status 0-1 * Life expectancy \>12 weeks * Adequate baseline organ functions, defined as: Serum creatinine less than or equal to (≤)1.5\*upper limit of normal (ULN). In case of borderline values for serum creatinine, creatinine clearance must be greater than or equal to (≥) 45 millimeters per minute (mL/min); Total bilirubin \<1.5\*ULN; Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5\*ULN (participants with liver metastases should have ALT/AST \<5\*ULN.); Absolute neutrophil count ≥1500per cubic millimeter(mm\^3); Platelet count ≥100000/mm\^3; Hemoglobin level ≥10 grams per deciliter * If procreative potential (male or female), willingness to use effective contraceptive methods for the duration of treatment and continuing for 2 months after the last dose. Participants of procreative potential are defined as any fertile male, or any female who has experienced menarche and who is not postmenopausal (defined as age-related amenorrhea ≥12 months) or who has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy)
Exclusion criteria
* Radiotherapy or major surgery within 30 days prior to the start of study treatment * Prior treatment with an EGFR-directed therapy or with EGFR signal transduction inhibitors * Prior treatment with pemetrexed * Pregnant (confirmed by beta-human chorionic gonadotropin \[β-HCG\]) or lactating female * Weight loss \>10% within 12 weeks prior to the start of study treatment * Documented or symptomatic brain metastases or leptomeningeal disease * Myocardial infarction within 6 months prior to the start of study treatment, uncontrolled congestive heart failure, or any current New York Heart Association Grade III or IV cardiovascular disorder despite treatment * Presence of a Grade ≥2 preexisting skin disorder (except for alopecia) * Previous diagnosis of autoimmune disease with significant organ involvement * Concurrent malignancies or invasive carcinomas diagnosed within the past 5 years, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix * Any significant disease that, in the Investigator's opinion, should exclude the participant from the study * History of significant neurologic or psychiatric disorder (for example, dementia, seizures, or bipolar disorder) * History of drug abuse within 6 months prior to the start of study treatment * Known conditions that require concurrent treatment with a nonpermitted drug * Presence of a contraindication to the study treatment(s) according to the current Investigator's Brochure (IB) for matuzumab and the labeling for pemetrexed * Known hypersensitivity to the study treatment or any of its components * Participation in another clinical study within 30 days prior to the start of study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response Assessed by Independent Review Committee | Baseline up to PD or death due to any cause (up to approximately 2 years) | Objective response was defined as having a complete response (CR) or a partial response (PR). Response assessment was performed using modified World Health Organization (WHO) criteria. Complete response: disappearance of all index and non-index lesions, without appearance of any new lesion. PR: greater than (\>) 50 percent (%) decrease from baseline in sum of product of diameters of index lesions, without appearance of any new lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Baseline up to PD or death due to any cause (up to approximately 3.5 years) | OS was defined as the duration from randomization to death (due to any cause). OS was estimated using Kaplan-Meier analysis. |
| Progression-Free Survival (PFS) | Baseline up to PD or death due to any cause (up to approximately 3.5 years) | PFS was defined as the time from randomization to the first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. PD: \>25% increase in one or more lesions, or appearance new lesions. PFS was estimated using Kaplan-Meier analysis. |
| Duration of Objective Response Assessed by Independent Review Committee | From first documented objective response to PD or death due to any cause (up to approximately 3.5 years) | Objective response was defined as having a CR or a PR. Response assessment was performed using modified WHO criteria. CR: disappearance of all index and non-index lesions, without appearance of any new lesion. PR: \>50% decrease from baseline in sum of product of diameters of index lesions, without appearance of any new lesion. Duration of objective response was defined as time from first appearance of CR or PR to time of PD (\>25% increase in one or more lesions, or appearance new lesions) or death. Duration of objective response was to be assessed using Kaplan-Meier analysis. |
| Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS) | Baseline, Cycle 2 (Cycle length = 3 weeks) | The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain\] and 3 items were global items (symptom distress, interference with activity level, and global QoL). The global QoL item scores are reported here. The total global QoL item score ranged from 0 (worse QoL) to 100 (best QoL). |
Countries
Austria, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed Alone Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks until PD or the occurrence of unacceptable toxicity. | 50 |
| Pemetrexed Plus Matuzumab 800 mg Per Week Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 800 mg IV infusion once every week. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity. | 51 |
| Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks Participants received pemetrexed 50 mg/m\^2 IV infusion every 3 weeks in combination with matuzumab 1600 mg IV infusion every 3 weeks. An observation period of at least 1 hour was specified between the end of the matuzumab infusion and the start of pemetrexed administration when these treatments were given on the same day. Treatment was continued until PD or the occurrence of unacceptable toxicity. | 47 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 | 1 |
| Overall Study | Death | 1 | 1 | 6 |
| Overall Study | Disease Progression | 30 | 33 | 33 |
| Overall Study | Logistical Constraint | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Other | 6 | 3 | 3 |
| Overall Study | Protocol Violation | 2 | 4 | 2 |
| Overall Study | Randomized but Not Treated | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Pemetrexed Alone | Pemetrexed Plus Matuzumab 800 mg Per Week | Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks | Total |
|---|---|---|---|---|
| Age, Continuous | 61 years | 62 years | 63 years | 62 years |
| Sex: Female, Male Female | 17 Participants | 16 Participants | 20 Participants | 53 Participants |
| Sex: Female, Male Male | 33 Participants | 35 Participants | 27 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 50 | 20 / 51 | 18 / 47 |
| serious Total, serious adverse events | 9 / 50 | 5 / 51 | 11 / 47 |
Outcome results
Primary
Number of Participants With Objective Response Assessed by Independent Review Committee
Objective response was defined as having a complete response (CR) or a partial response (PR). Response assessment was performed using modified World Health Organization (WHO) criteria. Complete response: disappearance of all index and non-index lesions, without appearance of any new lesion. PR: greater than (\>) 50 percent (%) decrease from baseline in sum of product of diameters of index lesions, without appearance of any new lesion.
Time frame: Baseline up to PD or death due to any cause (up to approximately 2 years)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pemetrexed Alone | Number of Participants With Objective Response Assessed by Independent Review Committee | 2 participants |
| Pemetrexed Plus Matuzumab 800 mg Per Week | Number of Participants With Objective Response Assessed by Independent Review Committee | 8 participants |
| Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks | Number of Participants With Objective Response Assessed by Independent Review Committee | 1 participants |
Secondary
Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS)
The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain\] and 3 items were global items (symptom distress, interference with activity level, and global QoL). The global QoL item scores are reported here. The total global QoL item score ranged from 0 (worse QoL) to 100 (best QoL).
Time frame: Baseline, Cycle 2 (Cycle length = 3 weeks)
Population: ITT population. Here, overall number of participants analyzed = participants with available data for this outcome; number analyzed = participants with available data at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pemetrexed Alone | Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS) | Baseline | 35.9 units on a scale | Standard Deviation 26 |
| Pemetrexed Alone | Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS) | Change at Cycle 2 | 3.5 units on a scale | Standard Deviation 17.2 |
| Pemetrexed Plus Matuzumab 800 mg Per Week | Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS) | Baseline | 31.1 units on a scale | Standard Deviation 25.8 |
| Pemetrexed Plus Matuzumab 800 mg Per Week | Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS) | Change at Cycle 2 | 0.8 units on a scale | Standard Deviation 19.9 |
| Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks | Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS) | Baseline | 35.8 units on a scale | Standard Deviation 27.5 |
| Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks | Change From Baseline to Cycle 2 in Global Quality of Life (QoL), as Assessed Using Lung Cancer Symptom Scale (LCSS) | Change at Cycle 2 | 15.7 units on a scale | Standard Deviation 30.7 |
Secondary
Duration of Objective Response Assessed by Independent Review Committee
Objective response was defined as having a CR or a PR. Response assessment was performed using modified WHO criteria. CR: disappearance of all index and non-index lesions, without appearance of any new lesion. PR: \>50% decrease from baseline in sum of product of diameters of index lesions, without appearance of any new lesion. Duration of objective response was defined as time from first appearance of CR or PR to time of PD (\>25% increase in one or more lesions, or appearance new lesions) or death. Duration of objective response was to be assessed using Kaplan-Meier analysis.
Time frame: From first documented objective response to PD or death due to any cause (up to approximately 3.5 years)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed Alone | Duration of Objective Response Assessed by Independent Review Committee | NA months |
| Pemetrexed Plus Matuzumab 800 mg Per Week | Duration of Objective Response Assessed by Independent Review Committee | NA months |
| Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks | Duration of Objective Response Assessed by Independent Review Committee | NA months |
Secondary
Overall Survival (OS)
OS was defined as the duration from randomization to death (due to any cause). OS was estimated using Kaplan-Meier analysis.
Time frame: Baseline up to PD or death due to any cause (up to approximately 3.5 years)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed Alone | Overall Survival (OS) | 7.9 months |
| Pemetrexed Plus Matuzumab 800 mg Per Week | Overall Survival (OS) | 12.4 months |
| Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks | Overall Survival (OS) | 5.9 months |
Secondary
Progression-Free Survival (PFS)
PFS was defined as the time from randomization to the first documentation of disease progression (PD) or to death due to any cause, whichever occurred first. PD: \>25% increase in one or more lesions, or appearance new lesions. PFS was estimated using Kaplan-Meier analysis.
Time frame: Baseline up to PD or death due to any cause (up to approximately 3.5 years)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pemetrexed Alone | Progression-Free Survival (PFS) | 2.7 months |
| Pemetrexed Plus Matuzumab 800 mg Per Week | Progression-Free Survival (PFS) | 2.3 months |
| Pemetrexed Plus Matuzumab 1600 mg Every 3 Weeks | Progression-Free Survival (PFS) | 2.5 months |