Clinical trial NCT01118676: Cilengitide Together With Radiochemotherapy in Patients With Locally Advanced Non Small Cell Lung Cancer
Official title: Phase I Trial Evaluating Continuous Infusion of Cilengitide Together With Radiochemotherapy in Patients With Locally Advanced Non Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Non Small Cell Lung Cancer (NSCLC)
Keywords: locally advanced non small cell lung cancer (NSCLC), locally advanced, Phase I, Cilengitide, concomitant radiochemotherapy
Lead sponsor: Institut Claudius Regaud
Sponsor class: OTHER
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2010-05-07
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a two-center study which includes 24 patients maximum on 36 months : 24 months accrual - 12 months follow up.

Eligible patients are included according to a standard 3+3 design.

Patients included in the trial will be treated with a combination of radiochemotherapy (standard radiotherapy of 66 Gy, 2 Gy per daily fraction, and cisplatin and vinorelbine based chemotherapy).

Cilengitide will be administered alone as continuous infusion two weeks before the radiochemotherapy and will then be continued during radiochemotherapy as continuous infusion.

The dose levels investigated will be applied to the continuous administration (a maximum of 4 dose levels).

After the end of concomitant radiochemotherapy, cilengitide will be administered i.v. at a dose of 2000 mg twice weekly until the end of chemotherapy.

The dose of Cilengitide administered after radiotherapy will not be increased. 4 dose levels are defined:12, 18, 27 et 40 mg /hour.


Eligibility criteria: Inclusion Criteria:

1. Histologically proven non small cell lung cancer
2. Inoperable tage IIIA or IIIB non small cell lung cancer
3. Age ≥ 18 years
4. PerfLife expectancy ≥6 months
5. Hematological function : neutrophils ≥1500/mm3 and platelets ≥ 100000/mm3
6. Hepatic function: Bilirubin within normal limits et AST and ALT ≤ 2 times the upper limit of normal (ULN).
7. Renal function: Creatinine ≤ 1.5 times ULN.
8. Absence of cardiac insufficiency, absence of unstable angina, absence of arrythmia
9. Patient has health insurance coverage.
10. Signed informed consent.

Exclusion Criteria:

1. Patients previously treated for a malignancy by means of chemotherapy, radiotherapy or surgery.
2. Uncontrolled hypertension
3. Uncontrolled bleeding within the last 3 months.
4. Patients under anti-coagulation with anti-vitamin K or therapeutic dose heparin ; low-molecular heparins for prophylaxis are permitted and are not considered an exclusion criterion.
5. Presence of cerebral metastases.
6. Participation in a clinical trial within the last 8 weeks.
7. Any other specific concomitant anti-tumor treatment (such as chemotherapy, radiotherapy ...).
8. Patients with a history of myocardial infarction or a cerebral vascular accident within the last 12 months.
9. Continued use of aspirin (\>325mg/day)
10. Major surgery whiting the last 28 days or planned.
11. Major non-healing wound, ulcer
12. Pregnant or breastfeeding women cannot participate in this trial. Women of reproductive potential must have a negative pregnancy test (blood) within 72 hours before the start of treatment.
13. Men and women of reproductive potential must use an efficient contraceptive method when entering the trial and until one months after the end of treatment.
14. History of a thrombo-embolic or hemorrhagic event.
15. Patients put under tutelage.
16. Patients not able to follow the procedures visits, exams foreseen by the trial.
17. Any other severe medical or psychiatric condition or biological anomaly - acute or chronic - that, in the investigator's opinion - may render the inclusion of the patient inappropriate.

Primary outcomes:
measure: To determine the Maximum Tolerated dose (MTD) of Cilengitide administered as continuous infusion during standard radiochemotherapy
timeFrame: at the end of the trial
Secondary outcomes:
measure: To determine the rate of objective response according to RECIST and pathological response.
timeFrame: at the end of the trial
measure: To determine the survival free of metastases and the survival without local relapse at one year.
timeFrame: at the end of the trial
measure: To determine the overall survival
timeFrame: at the end of the trial
measure: To determine the toxicity of the combination of radiochemotherapy and continuous infusion cilengitide as well as the toxicity of the combination of chemotherapy and twice weekly cilengitide.
timeFrame: at the end of the trial
measure: Ancillary studies will be undertaken to determine factors predictive of response to treatment and to characterize the anti-angiogenic effect of Cilengitide.
timeFrame: at the end of the trial
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU Toulouse Larrey
city: Toulouse
country: France
facility: Institut Claudius Regaud
Study officials:
affiliation: Institut Claudius Regaud
name: Elizabeth COHEN-JONATHAN MOYAL, Pr
role: PRINCIPAL_INVESTIGATOR
References: