NARLAL: Navelbine And Radiotherapy in Locally Advanced Lung Cancer

• Sponsor: Odense University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00887783
• Collaborator: Aarhus University Hospital (Other), Vejle Hospital (Other), Rigshospitalet, Denmark (Other), Aalborg University Hospital (Other), Copenhagen University Hospital at Herlev (Other)
• Enrollment: 117
• Locations: 6
• Arms: 2
• Actual Duration (Months): 88
• Patients Per Site: 19.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Navelbine; Radiation: 66 Gy/33F; Radiation: 60 Gy/30F	Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: No blinding after randomization
• Primary Purpose: Treatment
• Official Title: Induction Chemotherapy With Carboplatin and Navelbine Oral(R) Followed by Concomitant Navelbine Oral(R) and Irradiation in Local-regionally Advanced Non-small Cell Lung Cancer. A Randomized Phase II Study.
• Actual Study Start Date: May 1, 2009
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Navelbine; Navelbine oral 150 mg of Vinorelbine administered in 3 weekly doses a week for 6-6½ weeks; Other Names: Vinorelbine ; Radiation: 66 Gy/33F; irradiation to 66 Gy (2 Gy x 30, 5 F á weeks)
Active Comparator: 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	Drug: Navelbine; Navelbine oral 150 mg of Vinorelbine administered in 3 weekly doses a week for 6-6½ weeks; Other Names: Vinorelbine ; Radiation: 60 Gy/30F; irradiation to 60 Gy (2 Gy x 30, 5 F á weeks)

Outcome Measures

Primary Outcome Measures

1. Local Failure Free Survival [9 months]

   Local failure free survival 9 month after first RT treatment measured by CT/FDG-CT

Secondary Outcome Measures

1. Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy [9 months]

2. Local Tumour Control [9 months]

   Loco-regional control

3. Overall Survival [72 months]

   Overall survival, death of any cause

4. Late Toxicity [48 months]

   Late toxicity related to concurrent Vinorelbine and radiotherapy

5. Disease Free Survival [72 months]

   Disease free survival, death of any cause

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Oncology, Aalborg University Hospital	Aalborg		Denmark	9100
2	Department of Oncology, Aarhus University Hospital	Aarhus		Denmark	8000
3	Department of Oncology, Copenhagen University Hospital Herlev	Herlev		Denmark	2730
4	Department of Oncology, Odense University Hospital	Odense		Denmark	5000
5	Laboratory of Radiation Physics	Odense		Denmark	5000
6	Department of Oncology, Vejle Hospital	Vejle		Denmark	7100

Sponsors and Collaborators

• Odense University Hospital
• Aarhus University Hospital
• Vejle Hospital
• Rigshospitalet, Denmark
• Aalborg University Hospital
• Copenhagen University Hospital at Herlev

Investigators

• Principal Investigator: Olfred Hansen, MD, Odense University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Olfred Hansen, MD, Professor, Odense University Hospital
• ClinicalTrials.gov Identifier: NCT00887783
• Other Study ID Numbers: 09.01
• First Posted: Apr 24, 2009
• Last Update Posted: May 17, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Olfred Hansen, MD, Professor, Odense University Hospital: 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
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Vinorelbine

Study Results

Participant Flow

Recruitment Details	117 included July 2009 to August 2013

Arm/Group Title	B: 66Gy/33F+Navelbine Oral 150 mg q3w	A: 60Gy/30F+Navelbine Oral 150 mg q3w
Arm/Group Description	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)	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)
Period Title: Overall Study
STARTED	58	59
COMPLETED	58	59
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	B: 66Gy/33F+Navelbine Oral 150 mg q3w	A: 60Gy/30F+Navelbine Oral 150 mg q3w	Total
Arm/Group Description	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)	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)	Total of all reporting groups
Overall Participants	58	59	117
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	32 55.2%	22 37.3%	54 46.2%
>=65 years	26 44.8%	37 62.7%	63 53.8%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64.56	66.63	65.53
Sex: Female, Male (Count of Participants)
Female	26 44.8%	36 61%	62 53%
Male	32 55.2%	23 39%	55 47%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
Denmark	58 100%	59 100%	117 100%

Outcome Measures

1. Primary Outcome

Title	Local Failure Free Survival
Description	Local failure free survival 9 month after first RT treatment measured by CT/FDG-CT
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

Analyzed as intention to treat

Arm/Group Title	B: 66Gy/33F+Navelbine Oral 150 mg q3w	A: 60Gy/30F+Navelbine Oral 150 mg q3w
Arm/Group Description	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)	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)
Measure Participants	58	59
Median (Full Range) [months]	9.4	9.9

2. Secondary Outcome

Title	Number of Participants Who Experienced Early Toxicity to Concurrent Vinorelbine and Radiotherapy
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

Dysphagia, weight loss ≥20%, pulmonary toxicity grade 3, leucopenia grade 3 or higher

Arm/Group Title	B: 66Gy/33F+Navelbine Oral 150 mg q3w	A: 60Gy/30F+Navelbine Oral 150 mg q3w
Arm/Group Description	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)	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)
Measure Participants	58	59
Dysphagia g3+	7 12.1%	6 10.2%
Pulmonary tox	14 24.1%	11 18.6%
Leucopenia g3+	4 6.9%	3 5.1%

3. Secondary Outcome

Title	Local Tumour Control
Description	Loco-regional control
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival, death of any cause
Time Frame	72 months

Outcome Measure Data

Analysis Population Description

Overall survival, intention to treat

Arm/Group Title	B: 66Gy/33F+Navelbine Oral 150 mg q3w	A: 60Gy/30F+Navelbine Oral 150 mg q3w
Arm/Group Description	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)	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)
Measure Participants	58	59
Median (Full Range) [Months]	25.3	23.3

5. Secondary Outcome

Title	Late Toxicity
Description	Late toxicity related to concurrent Vinorelbine and radiotherapy
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Disease Free Survival
Description	Disease free survival, death of any cause
Time Frame	72 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	B: 66Gy/33F+Navelbine Oral 150 mg q3w	A: 60Gy/30F+Navelbine Oral 150 mg q3w
Arm/Group Description	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)	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)
Measure Participants	58	59
Median (Full Range) [Months]	8.4	8.8

Adverse Events

Time Frame	5 years, death or recurrence
Arm/Group Title	B: 66Gy/33F+Navelbine Oral 150 mg q3w		A: 60Gy/30F+Navelbine Oral 150 mg q3w
Arm/Group Description	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)		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)
All Cause Mortality
	B: 66Gy/33F+Navelbine Oral 150 mg q3w		A: 60Gy/30F+Navelbine Oral 150 mg q3w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/58 (70.7%)		44/59 (74.6%)
Serious Adverse Events
	B: 66Gy/33F+Navelbine Oral 150 mg q3w		A: 60Gy/30F+Navelbine Oral 150 mg q3w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/58 (31%)		15/59 (25.4%)
Blood and lymphatic system disorders
Atrial fibrilation	0/58 (0%)	0	2/59 (3.4%)	2
Gastrointestinal disorders
Dysphagia	8/58 (13.8%)	8	8/59 (13.6%)	8
Respiratory, thoracic and mediastinal disorders
Dyspnoea	15/58 (25.9%)	17	7/59 (11.9%)	7
Skin and subcutaneous tissue disorders
Herpes zoster	0/58 (0%)	0	1/59 (1.7%)	1
Other (Not Including Serious) Adverse Events
	B: 66Gy/33F+Navelbine Oral 150 mg q3w		A: 60Gy/30F+Navelbine Oral 150 mg q3w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/58 (43.1%)		20/59 (33.9%)
Blood and lymphatic system disorders
Leucopenia	4/58 (6.9%)	4	3/59 (5.1%)	3
Gastrointestinal disorders
Dysphagia	7/58 (12.1%)	7	6/59 (10.2%)	6
Respiratory, thoracic and mediastinal disorders
Pulmonary toxicity	14/58 (24.1%)	14	11/59 (18.6%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.