Clinical trial NCT01124812: 131I-L19SIP Radioimmunotherapy Combined With Radiochemotherapy in Patients With Locally-advanced Non Small Cell Lung Cancer (NSCLC)
Official title: A Prospective Non-randomized Study of 131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiotherapy (EBRT) and Concurrent Chemotherapy in Patients With Inoperable, Locally-advanced (Stage III) NSCLC
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Keywords: I131
L19
antibody
monoclonal
NSCLC
lung
tumor targeting
radioimmunotherapy
Patients with newly diagnosed inoperable, locally-advanced (stage III) NSCLC
Lead sponsor: Philogen S.p.A.
Sponsor class: INDUSTRY
First posted: 2010-05-17
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this feasibility study is to determine the therapeutic potential of the L19SIP antibody, labeled with the radionuclide 131I in combination with radiochemotherapy, for the treatment of patients with newly diagnosed, unresectable, locally-advanced NSCLC following the promising results with this agent in previous clinical studies.

The L19SIP antibody is a fully human antibody, capable of preferential localization around tumor blood vessels while sparing normal tissues. The formation of new blood vessels is a rare event in the adult (with the exception of the female reproductive tract), but it is a characteristic pathological feature for most types of aggressive cancer.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed unresectable stage III NSCLC
* Males or females, age ≥ 18 years
* Measurable lung lesion defined as at least one lesion that can be accurately and serially measured per the modified RECIST criteria.
* ECOG performance status \< 3
* Life expectancy of at least 12 weeks
* Patients eligible for concurrent radiochemotherapy (cisplatin/vinorelbine; 60-66 Gy EBRT) at the discretion of the clinical investigator
* Absolute neutrophil count \> 1.5 x 109/L, hemoglobin \> 9.0 g/dL and platelets \> 100 x 109/L
* Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/Dl)
* ALT and AST ≤ 2.5 x the upper limit of normal (5.0 x ULN for patients with hepatic involvement with tumor
* Serum creatinine \< 1.5 x ULN
* All toxic effects of prior therapy must have resolved to ≤ Grade 1 unless otherwise specified above
* Negative serum pregnancy test (for women of child-bearing potential only) at screening

Exclusion Criteria:

* Patients with metastatic disease
* Patients amenable for surgical resection of lung tumor lesions
* Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis \& Ti) or any cancer curatively treated \< 5 years prior to study entry
* History of HIV infection or infectious hepatitis B or C
* Presence of active infections (e.g. requiring antibimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
* Inadequately controlled cardiac arrhythmias including atrial fibrillation
* Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria)
* Uncontrolled hypertension
* Ischemic peripheral vascular disease (Grade IIb-IV)
* History of an acute cardiac event such as myocardial infarction, instable angina pectoris during the last 12 months
* Severe diabetic retinopathy
* Active autoimmune disease
* History of organ allograft or stem cell transplantation
* Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment
* Breast feeding female
* Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment
* Growth factors or immunomodulatory agents within 7 days of the administration of study treatment (131I-L19SIP application).
* Hyperthyroidism or autonomous thyroid nodule

Primary outcomes:
measure: Uptake of 131I-L19SIP or 124I-L19SIP
timeFrame: 2 days
measure: Safety and tolerability of 131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiotherapy (EBRT) and Concurrent Chemotherapy
timeFrame: 13 months
measure: Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose/Recommended Dose (MTD/RD) for the combination treatment
timeFrame: 4 weeks
Secondary outcomes:
measure: Overall response rate
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: University Hospital Pisa
state: Tuscany
city: Meldola
country: Italy
facility: Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)
Study officials:
affiliation: IRST - ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI - MELDOLA (FC)
name: Giovanni Paganelli, Dr
role: PRINCIPAL_INVESTIGATOR
References: