131I-L19SIP Radioimmunotherapy Combined With Radiochemotherapy in Patients With Locally-advanced Non Small Cell Lung Cancer (NSCLC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01124812
Recruitment Status : Terminated
First Posted : May 17, 2010
Last Update Posted : October 26, 2012
Information provided by (Responsible Party):
Philogen S.p.A.

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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Other: 131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiotherapy (EBRT) and Concurrent Chemotherapy Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2010
Actual Primary Completion Date : August 2011
Actual Study Completion Date : October 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 131I-L19SIP
131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiotherapy (EBRT) and Concurrent Chemotherapy: Treatment dose of 131I-L19SIP RIT is titrated in cohorts of 3 patients.
Other: 131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiotherapy (EBRT) and Concurrent Chemotherapy

Lung tumor irradiation with a total dosage of between 60-66 Gy, fractionated in combination with the following concurrent chemotherapy options:

  1. Cohorts 1, 2 & 3a is composed of cisplatin i.v. 80 mg/m2 on day 1, and vinorelbine i.v. 25 mg/m2 on day 1, 8, 15 for cycle 1 & 4. For patients with significant comorbidities, the dose of vinorelbine is reduced to 12.5 mg/m2 during cycles 2 & 3. Treatment cycles will be repeated every 28 days.
  2. Protocol A (suggested for patients with comorbidities: Carboplatin 70 mg/m2, over 30 min iv, (Day 1-5 ) + Vinorelbine 12.5 mg/m2 as a 5-min bolus iv or short iv-infusion (Day 1, 8, 22), repeated on Day 28.
  3. Protocol B (suggested for patients in good clinical condition): Paclitaxel 50 mg/m2 1 hour iv (Day 1, 15, 22, 29, 36, 43, 50) + Carboplatin AUC 2, 30 min iv on (Day 1, 15, 22, 29, 36, 43, 50).

    • Total treatment duration is 8-16 weeks

Primary Outcome Measures :
  1. Uptake of 131I-L19SIP or 124I-L19SIP [ Time Frame: 2 days ]
    The selective uptake of 131I-L19SIP or 124I-L19SIP in lung lesions and dosimetric analysis

  2. Safety and tolerability of 131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiotherapy (EBRT) and Concurrent Chemotherapy [ Time Frame: 13 months ]
    Safety will be assessed through physical examinations, vital signs, laboratory tests (including serum chemistries, hematology parameters) and the recording of adverse events. All results from these assessments will be coded using CTCAE v.3 and presented descriptively, indicating frequency and percentage of patients with adverse events, and abnormal laboratory tests. These results will be presented by related/unrelated and overall for the study.

  3. Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose/Recommended Dose (MTD/RD) for the combination treatment [ Time Frame: 4 weeks ]
    Dose limiting toxicities and maximum tolerated dose/recommended dose for the combination treatment

Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: 1 year ]
    Intrapulmonal, extra pulmonal and overall response rate

  2. Overall survival [ Time Frame: 1 year ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01124812

University Hospital Pisa
Pisa, Tuscany, Italy, 56126
Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)
Meldola, Italy
Sponsors and Collaborators
Philogen S.p.A.

Responsible Party: Philogen S.p.A. Identifier: NCT01124812     History of Changes
Other Study ID Numbers: PH-L19SIPI131-04/09
2009-017072-24 ( EudraCT Number )
First Posted: May 17, 2010    Key Record Dates
Last Update Posted: October 26, 2012
Last Verified: June 2012

Keywords provided by Philogen S.p.A.:
tumor targeting
Patients with newly diagnosed inoperable, locally-advanced (stage III) NSCLC

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms