Non-Small-Cell Lung Cancer
Conditions
Keywords
Non-Small-Cell Lung Cancer, NSCLC, Panitumumab, Vectibix, Pemetrexed, Alimta, Carboplatin
Brief summary
The purpose of this multicenter, Phase II trial is to examine the role of a well-tolerated novel agent, panitumumab, in combination with a modern platinum doublet regimen using carboplatin and pemetrexed, in patients with advanced non-squamous wild type K-ras non-small-cell lung cancer (NSCLC). If this treatment proves to be well tolerated and associated with efficacy, this would provide rationale for further randomized studies.
Interventions
DRUGCarboplatin
Carboplatin AUC=6IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length)
DRUGPemetrexed
Pemetrexed 500mg/m² IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length)
DRUGPanitumumab
Panitumumab 9mg/kg IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length)
Sponsors
Amgen
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Histologically confirmed non-squamous NSCLC (squamous cell histology is ineligible). Cytologic specimens obtained by brushings, washings or needle aspiration of the defined lesion are acceptable. Sputum cytology alone is not acceptable. Mixed tumors with small cell elements are not eligible. 3. Newly diagnosed unresectable stage IIIB or stage IV disease. Patients with stage IIIB disease should be ineligible for combined modality therapy (i.e., pleural effusions, pericardial effusions, etc.). 4. At least one unidimensionally measurable lesion definable by magnetic resonance imaging (MRI) or computed tomography (CT) scan. Measurable disease is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. 5. Demonstration of K-ras wild type in archived tumor tissue. Tissue must be available for testing or results from previous K-ras testing must be available at the time of registration. 6. No prior antineoplastic chemotherapy for metastatic lung cancer. Patients may have received adjuvant treatment for stage I, II or III disease. 7. For patients who have had previous radiotherapy as definitive therapy for locally advanced NSCLC, recurrence must be outside of the original radiation therapy port. Radiation therapy must have been completed more than four weeks prior to study entry. Previous radiation must have covered \< 30% of marrow bearing area. 8. Full recovery from surgery for patients who have undergone thoracotomy. Patients cannot start protocol treatment until at least three weeks after an operative procedure. 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 10. Life expectancy ≥ 12 weeks. 11. Normal bone marrow function within 7 days prior to initial treatment as defined by: * absolute neutrophil count (ANC) ≥1500/µL * platelets ≥100,000/µL * hemoglobin ≥8.0 g/dL. Patients may receive transfusions or erythropoietin to maintain or exceed this level. 12. Normal hepatic function as defined by: * bilirubin ≤1.5 x institutional upper limit of normal (ULN). * transaminases ≤2.5 x institutional ULN. In the presence of known hepatic metastases, transaminases may be ≤5 x institutional ULN. 13. Normal renal function within 7 days prior to initial treatment as defined by: * serum creatinine \<2.0 mg/dL * estimated creatinine clearance (CrCl) ≥ 45 mL/min calculated by the Cockcroft-Gault method. 14. Normal metabolic function as follows: • Magnesium ≥ institutional lower limit of normal (LLN) 15. The ability to take folic acid, vitamin B12, and dexamethasone according to the protocol. 16. The ability to interrupt non-steroidal anti-inflammatory drugs (NSAIDs) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed. 17. Negative serum or urine pregnancy test within 7 days prior to initial study treatment. 18. Agreement of women of child-bearing potential (WOCBP) and men to use adequate contraception (hormonal or barrier method of birth control; abstinence) to prevent contraception during treatment and for a minimum of 6 months after the last study treatment. 19. Willingness and ability to comply with study and follow-up procedures. 20. Ability to understand the nature of this study and give written informed consent.
Exclusion criteria
1. NSCLC with squamous cell histology. 2. History of any invasive cancer treated within the previous 5 years with the exception of the disease under study, curatively treated non melanoma skin cancer or carcinoma in situ of the cervix. 3. Prior therapy which specifically and directly targets the EGFR pathway (e.g., cetuximab, gefitinib, erlotinib, lapatinib). 4. Active brain or meningeal metastases. Patients must have completed any previous radiotherapy at least four weeks prior to study entry and recovered from any toxicity associated with radiotherapy. Patients must have no on-going requirement for and must have discontinued corticosteroids. 5. Pregnancy or breast-feeding. 6. A serious active infection at the time of treatment or other serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. 7. Acute hepatitis or known human immunodeficiency virus (HIV) infection. 8. Presence of third space fluid which is clinically significant and cannot be controlled by drainage. 9. History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan). 10. History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results. 11. Prior severe infusion reaction to a monoclonal antibody or history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study (e.g., carboplatin, pemetrexed).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Progression (TTP) | 18 months | Defined as the time between Day 1-Cycle 1 and date of first documented disease progression assessed using Response Evaluation Criteria in Solid Tumors (RECISTS) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-free Survival (PFS) | Assessments by clinical evaluation, radiographic status, and date of disease progression, estimated 18 months | Defined as the time between Day 1-Cycle 1 and date of first documented disease progression or death. |
| Median Overall Survival (OS) | 18 months | Defined as the time between Day 1-Cycle 1 to the date of death from any cause. |
| Objective Response Rate | Projected 18 months | — |
| Frequency of Adverse Events and Severity as a Measure of Toxicity | Every 3 weeks (1 cycle) for 6 cycles, then every 7 weeks thereafter | Assessed using NCI CTCAE v4.0 |
Countries
United States
Participant flow
Pre-assignment details
One patient signed the consent but had a stroke prior to the pre-treatment and Cycle 1-Day 1 visits.
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin/Pemetrexed/Panitumumab Systemic Therapy
Carboplatin: Carboplatin AUC=6IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length)
Pemetrexed: Pemetrexed 500mg/m² IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length)
Panitumumab: Panitumumab 9mg/kg IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length) | 69 |
| Total | 69 |
Baseline characteristics
| Characteristic | Carboplatin/Pemetrexed/Panitumumab |
|---|---|
| Age, Continuous | 65 years |
| Region of Enrollment United States | 69 participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 67 / 69 |
| serious Total, serious adverse events | 24 / 69 |
Outcome results
Primary
Median Time to Progression (TTP)
Defined as the time between Day 1-Cycle 1 and date of first documented disease progression assessed using Response Evaluation Criteria in Solid Tumors (RECISTS) v1.1.
Time frame: 18 months
Population: All enrolled and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Pemetrexed/Panitumumab | Median Time to Progression (TTP) | 6.11 months |
Secondary
Frequency of Adverse Events and Severity as a Measure of Toxicity
Assessed using NCI CTCAE v4.0
Time frame: Every 3 weeks (1 cycle) for 6 cycles, then every 7 weeks thereafter
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Rash | 55 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Nausea | 39 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Fatigue | 33 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Hypomagnesemia | 30 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Neutrophil Count Decreased | 30 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Platelet Count Decreased | 29 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Anemia | 28 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Mucositis | 23 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Dry Skin | 22 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Anorexia | 19 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Diarrhea | 19 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Constipation | 17 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | White Blood Cell Decreased | 16 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Pruritus | 15 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Vomiting | 15 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Dehydration | 13 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Dysgeusia | 12 participants |
| Carboplatin/Pemetrexed/Panitumumab | Frequency of Adverse Events and Severity as a Measure of Toxicity | Alopecia | 11 participants |
Secondary
Median Overall Survival (OS)
Defined as the time between Day 1-Cycle 1 to the date of death from any cause.
Time frame: 18 months
Population: All enrolled and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Pemetrexed/Panitumumab | Median Overall Survival (OS) | 17.02 months |
Secondary
Median Progression-free Survival (PFS)
Defined as the time between Day 1-Cycle 1 and date of first documented disease progression or death.
Time frame: Assessments by clinical evaluation, radiographic status, and date of disease progression, estimated 18 months
Population: All enrolled and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Pemetrexed/Panitumumab | Median Progression-free Survival (PFS) | 5.75 months |
Secondary
Objective Response Rate
Time frame: Projected 18 months
Population: All patients evaluated for response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Carboplatin/Pemetrexed/Panitumumab | Objective Response Rate | 53 percentage of evaluated participants |