Chemoradiotherapy in Stage III Non-small Cell Lung Cancer (NSCLC)

• Sponsor: Intergroupe Francophone de Cancerologie Thoracique (Other)
• Overall Status: Completed
• CT.gov ID: NCT01102231
• Collaborator: (none)
• Enrollment: 106
• Locations: 38
• Arm: 1
• Actual Duration (Months): 69
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Radiochemotherapy is a standard for the treatment of unresectable stage III non-small cell lung cancer. The investigators goal is to study the efficacy and the toxicity for a promising association of new agents (cetuximab and pemetrexed) with concurrent radiotherapy.

Condition or Disease	Intervention/Treatment	Phase
Stage III Non-small Cell Lung Cancer	Drug: Chemotherapy; Drug: ERBITUX; Radiation: Radiotherapy	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Pemetrexed + Cetuximab + Cisplatin With Concurrent Chemoradiotherapy in Stage III Non-small Cell Lung Cancer (NSCLC)
• Actual Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Chemoradiotherapy	Drug: Chemotherapy; Pemetrexed 500 mg/m², D1 (D1=D22, 4 cycles) Cisplatin 75 mg/m², D1 (D1=D22, 4 cycles); Drug: ERBITUX; The initial dose of cetuximab (ERBITUX) is 400 mg/m² intravenously administered over 120 minutes, followed by 11 weekly infusions at 250 mg/m² IV over 60 minutes; Radiation: Radiotherapy; 66 Gy (2 Gy by fraction, 5 fractions by week)

Outcome Measures

Primary Outcome Measures

1. Disease-Control Rate [16 weeks after inclusion]

   percentage of patients with disease control (complete response + partial response + stable disease) according to RECIST 1.1 criteria Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for Progressive Disease (at least a 20% increase in the sum of diameters of target lesions).

Secondary Outcome Measures

1. 18-month Overall Survival Rate [18 months]

   Percentage of patient alive 18 months after registration

2. Progression Free Survival [52.3 months (median duration of follow-up)]

   Progression-free survival is defined as time between date of inclusion and progression or all-cause death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• non-squamous stage III non-small cell lung cancer

• measurable disease (RECIST 1.1)

• ECOG performance status 0-1

• normal organ and marrow function

Exclusion Criteria:

• prior chest radiation therapy

• history of any cancer other than NSCLC (except non-melanoma skin cancer or carcinoma in situ of the cervix) within the last five years.

• Prior therapy with known specific inhibitors of the EGFR.

• history of severe allergic reaction to prior therapy with monoclonal antibodies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinique de l'Europe	Amiens		France
2	Centre Hospitalier	Annemasse		France
3	CHU Besancon - Pneumologie	Besancon		France	25000
4	Bordeaux - Polyclinique Nord	Bordeaux		France	33300
5	Caen - Centre François Baclesse	Caen		France	14000
6	Caen - CHU Côte de Nacre	Caen		France	14000
7	CH	Chartres		France
8	CH	Cholet		France
9	CHU	Clermont-Ferrand		France
10	CH	Colmar		France
11	Clinique des Cèdres	Cornebarrieu		France
12	Dijon - CAC	Dijon		France	21000
13	CHU Grenoble	Grenoble		France	38000
14	Institut d'Oncologie Hartmann	Levallois		France
15	CHU (Hôpital Calmette) - Pneumologie	Lille		France	59000
16	CH	Longjumeau		France
17	Clinique des 4 Pavillons	Lormont		France
18	Hôpital Louis Pradel	Lyon		France
19	Hôpital Nord	Marseille		France
20	Centre Hospitalier	Montélimar		France
21	CHU	Nancy		France
22	CH	Nevers		France
23	Centre Hospitalier	Niort		France
24	APHP - Hopital Tenon - Pneumologie	Paris		France	75020
25	Hôpital du Val de Grâce	Paris		France
26	Hôpital Saint-Joseph	Paris		France
27	Perpignan - Centre Catalan d'Oncologie	Perpignan		France	66000
28	HCL - Lyon Sud	Pierre Bénite		France	69495
29	CHU	Poitiers		France
30	Centre Hospitalier	Rambouillet		France
31	Reims - CHU	Reims		France	51092
32	Institut Jean Godinot	Reims		France
33	Centre Frederic Joliot	Rouen		France
34	Centre Etienne Dolet	Saint-Nazaire		France
35	Hôpitaux Universitaires - Nouvel Hôpital Civil	Strasbourg		France	63000
36	Suresnes - Hopital Foch	Suresnes		France	92151
37	Tours - CHU	Tours		France	37000
38	Institut Gustave Roussy	Villejuif		France	94800

Sponsors and Collaborators

• Intergroupe Francophone de Cancerologie Thoracique

Investigators

• Principal Investigator: Jean Trédaniel, MD, PhD, IFCT, GH Paris Saint-Joseph
• Principal Investigator: Françoise Mornex, MD, PhD, IFCT, HCL Lyon-Sud

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• IFCT official website

Publications

• Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignon JP. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010 May 1;28(13):2181-90. doi: 10.1200/JCO.2009.26.2543. Epub 2010 Mar 29. Review.
• Tredaniel J, Mornex F, Barillot I, Diaz O, Hennequin C, Le Pechoux C, Lavole A, Giraud P, Souquet PJ, Teixeira L, Vaylet F, Zalcman G, Baudrin L, Morin F, Milleron B. [A phase II study of cetuximab, pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non squamous, non-small cell lung cancer (NSCLC)]. Rev Mal Respir. 2011 Jan;28(1):51-7. doi: 10.1016/j.rmr.2010.06.027. Epub 2011 Jan 11. French.

• Responsible Party: Intergroupe Francophone de Cancerologie Thoracique
• ClinicalTrials.gov Identifier: NCT01102231
• Other Study ID Numbers: IFCT-0803
• First Posted: Apr 13, 2010
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Cetuximab

Study Results

Participant Flow

Arm/Group Title	Chemoradiotherapy + Cetuximab
Arm/Group Description	Chemotherapy + cetuximab + radiotherapy Chemotherapy: Pemetrexed 500 mg/m², D1 (D1=D22, 4 cycles) Cisplatin 75 mg/m², D1 (D1=D22, 4 cycles) ERBITUX: The initial dose of cetuximab (ERBITUX) is 400 mg/m² intravenously administered over 120 minutes, followed by 11 weekly infusions at 250 mg/m² IV over 60 minutes Radiotherapy: 66 Gy (2 Gy by fraction, 5 fractions by week)
Period Title: Overall Study
STARTED	106
COMPLETED	91
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Chemoradiotherapy + Cetuximab
Arm/Group Description	Chemoradiotherapy Chemotherapy: Pemetrexed 500 mg/m², D1 (D1=D22, 4 cycles) Cisplatin 75 mg/m², D1 (D1=D22, 4 cycles) ERBITUX: The initial dose of cetuximab (ERBITUX) is 400 mg/m² intravenously administered over 120 minutes, followed by 11 weekly infusions at 250 mg/m² IV over 60 minutes Radiotherapy: 66 Gy (2 Gy by fraction, 5 fractions by week)
Overall Participants	106
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57.32
Sex: Female, Male (Count of Participants)
Female	39 36.8%
Male	67 63.2%
Region of Enrollment (participants) [Number]
France	106 100%
Smoker (Count of Participants)
Count of Participants [Participants]	100 94.3%
Stage (Count of Participants)
IIIA	53 50%
IIIB	51 48.1%
IV	2 1.9%
Histological subtype (Count of Participants)
Sarcomatoid	2 1.9%
Adenosquamous	1 0.9%
Adenocarcinoma without bronchoalveolar component	82 77.4%
Non Small Cell	14 13.2%
Neuroendocrine carcinoma	1 0.9%
Non Squamous Non Small Cell	6 5.7%
ECOG Performance status (Count of Participants)
PS = 0	63 59.4%
PS = 1	43 40.6%
Unresectability cause (Count of Participants)
Anatomical	100 94.3%
Functional	6 5.7%

Outcome Measures

1. Primary Outcome

Title	Disease-Control Rate
Description	percentage of patients with disease control (complete response + partial response + stable disease) according to RECIST 1.1 criteria Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for Progressive Disease (at least a 20% increase in the sum of diameters of target lesions).
Time Frame	16 weeks after inclusion

Outcome Measure Data

Analysis Population Description

Eligible population

Arm/Group Title	Chemoradiotherapy + Cetuximab
Arm/Group Description	Chemoradiotherapy Chemotherapy: Pemetrexed 500 mg/m², D1 (D1=D22, 4 cycles) Cisplatin 75 mg/m², D1 (D1=D22, 4 cycles) ERBITUX: The initial dose of cetuximab (ERBITUX) is 400 mg/m² intravenously administered over 120 minutes, followed by 11 weekly infusions at 250 mg/m² IV over 60 minutes Radiotherapy: 66 Gy (2 Gy by fraction, 5 fractions by week)
Measure Participants	99
Count of Participants [Participants]	89 84%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemoradiotherapy + Cetuximab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion difference
	Estimated Value	0.905
	Confidence Interval	(2-Sided) 95%; 0.846 to 0.964
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	18-month Overall Survival Rate
Description	Percentage of patient alive 18 months after registration
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Eligible population

Arm/Group Title	Chemoradiotherapy + Cetuximab
Arm/Group Description	Chemoradiotherapy Chemotherapy: Pemetrexed 500 mg/m², D1 (D1=D22, 4 cycles) Cisplatin 75 mg/m², D1 (D1=D22, 4 cycles) ERBITUX: The initial dose of cetuximab (ERBITUX) is 400 mg/m² intravenously administered over 120 minutes, followed by 11 weekly infusions at 250 mg/m² IV over 60 minutes Radiotherapy: 66 Gy (2 Gy by fraction, 5 fractions by week)
Measure Participants	99
Number (95% Confidence Interval) [percentage of participant]	42.4

3. Secondary Outcome

Title	Progression Free Survival
Description	Progression-free survival is defined as time between date of inclusion and progression or all-cause death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	52.3 months (median duration of follow-up)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemoradiotherapy + Cetuximab
Arm/Group Description	Chemotherapy + cetuximab + radiotherapy Chemotherapy: Pemetrexed 500 mg/m², D1 (D1=D22, 4 cycles) Cisplatin 75 mg/m², D1 (D1=D22, 4 cycles) ERBITUX: The initial dose of cetuximab (ERBITUX) is 400 mg/m² intravenously administered over 120 minutes, followed by 11 weekly infusions at 250 mg/m² IV over 60 minutes Radiotherapy: 66 Gy (2 Gy by fraction, 5 fractions by week)
Measure Participants	99
Median (95% Confidence Interval) [Months]	14.4

Adverse Events

Time Frame	Adverse event were collected for a patient from the date of signature of his inform consent form until 30 days after the end of his study treatment. Deaths were collected through study completion.
Arm/Group Title	Chemoradiotherapy + Cetuximab
Arm/Group Description	Chemotherapy + cetuximab + radiotherapy Chemotherapy: Pemetrexed 500 mg/m², D1 (D1=D22, 4 cycles) Cisplatin 75 mg/m², D1 (D1=D22, 4 cycles) ERBITUX: The initial dose of cetuximab (ERBITUX) is 400 mg/m² intravenously administered over 120 minutes, followed by 11 weekly infusions at 250 mg/m² IV over 60 minutes Radiotherapy: 66 Gy (2 Gy by fraction, 5 fractions by week)
All Cause Mortality
	Chemoradiotherapy + Cetuximab
	Affected / at Risk (%)	# Events
Total	51/102 (50%)
Serious Adverse Events
	Chemoradiotherapy + Cetuximab
	Affected / at Risk (%)	# Events
Total	26/102 (25.5%)
Blood and lymphatic system disorders
Bone marrow failure	1/102 (1%)	1
Febrile bone marrow aplasia	1/102 (1%)	1
Febrile neutropenia	5/102 (4.9%)	5
Anemia	1/102 (1%)	1
Cardiac disorders
Atrial fibrillation	1/102 (1%)	1
Myocardial infarction	1/102 (1%)	1
Pericardial effusion	2/102 (2%)	2
Tachycardia	1/102 (1%)	1
Eye disorders
Eye pain	1/102 (1%)	1
Gastrointestinal disorders
Colitis	1/102 (1%)	1
Constipation	1/102 (1%)	1
Dysphagia	3/102 (2.9%)	4
Abdominal pain	1/102 (1%)	1
Faecaloma	1/102 (1%)	1
Nausea	3/102 (2.9%)	3
Oesophagitis	4/102 (3.9%)	4
Vomiting	4/102 (3.9%)	5
Aphasia	1/102 (1%)	1
General disorders
Asthenia	2/102 (2%)	2
Fatigue	1/102 (1%)	1
General physical health deterioration	7/102 (6.9%)	7
Death	1/102 (1%)	1
Hyperthermia	1/102 (1%)	1
Malaise	1/102 (1%)	1
Pyrexia	1/102 (1%)	1
Hepatobiliary disorders
Cholecystitis	2/102 (2%)	2
Immune system disorders
Hypersensitivity	1/102 (1%)	1
Infections and infestations
device related infection	3/102 (2.9%)	3
Sepsis	2/102 (2%)	2
Urinary tract infection	1/102 (1%)	1
Infection	1/102 (1%)	1
Infective exacerbation of chronic obstructive airways disease	1/102 (1%)	1
Investigations
Hemoglobin decreased	2/102 (2%)	2
Neutrophil count decreased	2/102 (2%)	2
Platelet count decreased	2/102 (2%)	2
Metabolism and nutrition disorders
decreased appetite	2/102 (2%)	2
Dehydratation	1/102 (1%)	1
Hypocalcemia	1/102 (1%)	1
Hypokalemia	3/102 (2.9%)	3
Musculoskeletal and connective tissue disorders
Back pain	1/102 (1%)	1
Nervous system disorders
Carotid artery aneurysm	1/102 (1%)	1
Renal and urinary disorders
Acute kidney injury	1/102 (1%)	1
Hematuria	1/102 (1%)	1
Renal failure	2/102 (2%)	3
Respiratory, thoracic and mediastinal disorders
Hemoptysis	1/102 (1%)	1
Lung disorder	3/102 (2.9%)	3
Respiratory failure	1/102 (1%)	1
Respiratory tract infection	1/102 (1%)	3
Asthma	1/102 (1%)	1
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	1/102 (1%)	1
Vascular disorders
Phlebitis superficial	1/102 (1%)	1
Pulmonary embolism	4/102 (3.9%)	4
Other (Not Including Serious) Adverse Events
	Chemoradiotherapy + Cetuximab
	Affected / at Risk (%)	# Events
Total	100/102 (98%)
Blood and lymphatic system disorders
Neutrophil count decreased	80/102 (78.4%)	234
Platelet count decreased	62/102 (60.8%)	178
Ear and labyrinth disorders
Tinnitus	10/102 (9.8%)	28
Eye disorders
Conjunctivitis	9/102 (8.8%)	13
Gastrointestinal disorders
Anorexia	45/102 (44.1%)	106
Constipation	39/102 (38.2%)	83
Diarrhea	23/102 (22.5%)	34
dysgueusia	6/102 (5.9%)	8
dysphagia	65/102 (63.7%)	181
Gastralgia	8/102 (7.8%)	12
Nausea	76/102 (74.5%)	217
Oral mucosal irritation	44/102 (43.1%)	92
Pyrosis	6/102 (5.9%)	10
Vomiting	37/102 (36.3%)	69
General disorders
Alopecia	14/102 (13.7%)	28
Asthenia	78/102 (76.5%)	250
Chest pain	19/102 (18.6%)	47
Edema limb	7/102 (6.9%)	10
Fever	14/102 (13.7%)	23
Vertigo	6/102 (5.9%)	10
Weight loss	19/102 (18.6%)	50
Infections and infestations
Mycosis	6/102 (5.9%)	7
Investigations
Hemoglobin decreased	63/102 (61.8%)	217
Metabolism and nutrition disorders
Hypokalemia	7/102 (6.9%)	14
Nervous system disorders
Neuropathy	7/102 (6.9%)	8
Paresthesia	7/102 (6.9%)	12
Renal and urinary disorders
Renal failure	8/102 (7.8%)	21
Respiratory, thoracic and mediastinal disorders
Cough	38/102 (37.3%)	94
Dysphonia	10/102 (9.8%)	28
Dyspnea	39/102 (38.2%)	94
Epistaxis	13/102 (12.7%)	16
Hemoptysis	6/102 (5.9%)	9
Skin and subcutaneous tissue disorders
Acne	23/102 (22.5%)	80
Dermatitis	27/102 (26.5%)	58
Dry skin	30/102 (29.4%)	92
Erythema	21/102 (20.6%)	46
Folliculitis	36/102 (35.3%)	124
Paronychia	7/102 (6.9%)	10
Pruritus	7/102 (6.9%)	10
Rash	32/102 (31.4%)	114
Skin disorder	16/102 (15.7%)	46

Limitations/Caveats

Non randomized study

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.