Non-small Cell Lung Cancer
Conditions
Keywords
Induction chemotherapy, Non-small cell lung cancer, Randomized phase II study, Navelbine Oral (R), 3D-conformal radiotherapy, Chemo-radiotherapy, Local-regionally advanced non-small cell lung cancer
Brief summary
This study is an open label randomized multi-centre phase II trial in patients with inoperable locally advanced stage IIB-IIIB Non Small Cell Lung Cancer who fulfils the general criteria for curatively intended irradiation. The treatment plan consists of two courses of inductions chemotherapy followed of concomitant therapy chemo-radiotherapy 3 weeks after day 1 of the last induction chemotherapy has been given. The patients will be included in the study after completing the induction chemotherapy. Randomization will take place only if an acceptable dose plan can be obtained.
Detailed description
This study was an open label randomized multi-centre phase II trial in patients with inoperable locally advanced stage IIB-IIIB Non Small Cell Lung Cancer who fulfils the general criteria for curatively intended irradiation. The treatment plan consisted of two courses of inductions chemotherapy followed of concomitant therapy chemo-radiotherapy 3 weeks after day 1 of the last induction chemotherapy has been given. The patients was included in the study after completing the induction chemotherapy. Randomization took place only if an acceptable dose plan could be obtained. Primary endpoint: local recurrence free interval
Interventions
DRUGNavelbine
Navelbine oral 150 mg of Vinorelbine administered in 3 weekly doses a week for 6-6½ weeks
RADIATION66 Gy/33F
irradiation to 66 Gy (2 Gy x 30, 5 F á weeks)
RADIATION60 Gy/30F
irradiation to 60 Gy (2 Gy x 30, 5 F á weeks)
Sponsors
Aarhus University Hospital
Vejle Hospital
Rigshospitalet, Denmark
Aalborg University Hospital
Copenhagen University Hospital at Herlev
Odense University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
No blinding after randomization
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Patients with histologically or cytologically documented diagnosis of locally advanced NSCLC stage IIB to IIIB without pleural effusion * Performance status 0-1 on the ECOG scale * Weight loss ≤10% during the last 6 months * Adequate lung function measured as FEV1 ≥1.0 * Neutrophile count ≥1.5 x 109/L and platelet count ≥100 x 109/L * Serum bilirubin ≤1.5 upper limit of normal (ULN) * ALAT ≤2 x ULN * Able to comply with study and follow-up procedures * Patients with reproductive potential must use effective contraception * Written (signed) informed consent to participate in the study
Exclusion criteria
* Any unstable systemic disease (including active infection, unstable angina, congestive heart failure, severe hepatic, renal, or metabolic disease) * Any other active malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer) * Prior chemotherapy for lung cancer, including neo- and adjuvant chemotherapy * Inability to take oral medication, or requirement of intravenous alimentation * Active peptic ulcer disease * Nursing mothers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Failure Free Survival | 9 months | Local failure free survival 9 month after first RT treatment measured by CT/FDG-CT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy | 9 months | — |
| Local Tumour Control | 9 months | Loco-regional control |
| Overall Survival | 72 months | Overall survival, death of any cause |
| Late Toxicity | 48 months | Late toxicity related to concurrent Vinorelbine and radiotherapy |
| Disease Free Survival | 72 months | Disease free survival, death of any cause |
Countries
Denmark
Participant flow
Recruitment details
117 included July 2009 to August 2013
Participants by arm
| Arm | Count |
|---|---|
| B: 66Gy/33F+Navelbine Oral 150 mg q3w Navelbine oral 150 mg of Vinorelbine administered in 3 weekly doses a week for 6-6½ weeks concomitant with curatively intended irradiation to 66 Gy (2 Gy x 30, 5 F á weeks).
Radiation technique: 3D, 4D og VMAT techniques. The patients all had 2 cycles of carboplatin and vinorelbine before randomization
Navelbine: Navelbine oral 150 mg of Vinorelbine administered in 3 weekly doses a week for 6-6½ weeks
66 Gy/33F: irradiation to 66 Gy (2 Gy x 30, 5 F á weeks) | 58 |
| A: 60Gy/30F+Navelbine Oral 150 mg q3w Navelbine oral 150 mg of Vinorelbine administered in 3 weekly doses a week for 6-6½ weeks concomitant with curatively intended irradiation to 60 Gy (2 Gy x 30, 5 F á weeks) Radiation technique: 3D, 4D og VMAT techniques. The patients all had 2 cycles of carboplatin and vinorelbine before randomization
Navelbine: Navelbine oral 150 mg of Vinorelbine administered in 3 weekly doses a week for 6-6½ weeks
60 Gy/30F: irradiation to 60 Gy (2 Gy x 30, 5 F á weeks) | 59 |
| Total | 117 |
Baseline characteristics
| Characteristic | A: 60Gy/30F+Navelbine Oral 150 mg q3w | Total | B: 66Gy/33F+Navelbine Oral 150 mg q3w |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 37 Participants | 63 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 54 Participants | 32 Participants |
| Age, Continuous | 66.63 years | 65.53 years | 64.56 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Denmark | 59 Participants | 117 Participants | 58 Participants |
| Sex: Female, Male Female | 36 Participants | 62 Participants | 26 Participants |
| Sex: Female, Male Male | 23 Participants | 55 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 41 / 58 | 44 / 59 |
| other Total, other adverse events | 25 / 58 | 20 / 59 |
| serious Total, serious adverse events | 18 / 58 | 15 / 59 |
Outcome results
Primary
Local Failure Free Survival
Local failure free survival 9 month after first RT treatment measured by CT/FDG-CT
Time frame: 9 months
Population: Analyzed as intention to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| B: 66Gy/33F+Navelbine Oral 150 mg q3w | Local Failure Free Survival | 9.4 months |
| A: 60Gy/30F+Navelbine Oral 150 mg q3w | Local Failure Free Survival | 9.9 months |
Secondary
Disease Free Survival
Disease free survival, death of any cause
Time frame: 72 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| B: 66Gy/33F+Navelbine Oral 150 mg q3w | Disease Free Survival | 8.4 Months |
| A: 60Gy/30F+Navelbine Oral 150 mg q3w | Disease Free Survival | 8.8 Months |
Secondary
Late Toxicity
Late toxicity related to concurrent Vinorelbine and radiotherapy
Time frame: 48 months
Secondary
Local Tumour Control
Loco-regional control
Time frame: 9 months
Secondary
Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy
Time frame: 9 months
Population: Dysphagia, weight loss ≥20%, pulmonary toxicity grade 3, leucopenia grade 3 or higher
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| B: 66Gy/33F+Navelbine Oral 150 mg q3w | Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy | Pulmonary tox | 14 participants |
| B: 66Gy/33F+Navelbine Oral 150 mg q3w | Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy | Dysphagia g3+ | 7 participants |
| B: 66Gy/33F+Navelbine Oral 150 mg q3w | Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy | Leucopenia g3+ | 4 participants |
| A: 60Gy/30F+Navelbine Oral 150 mg q3w | Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy | Pulmonary tox | 11 participants |
| A: 60Gy/30F+Navelbine Oral 150 mg q3w | Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy | Dysphagia g3+ | 6 participants |
| A: 60Gy/30F+Navelbine Oral 150 mg q3w | Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy | Leucopenia g3+ | 3 participants |
Secondary
Overall Survival
Overall survival, death of any cause
Time frame: 72 months
Population: Overall survival, intention to treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| B: 66Gy/33F+Navelbine Oral 150 mg q3w | Overall Survival | 25.3 Months |
| A: 60Gy/30F+Navelbine Oral 150 mg q3w | Overall Survival | 23.3 Months |