Radioimmunotherapy With 131I-L19SIP in Patients With Cancer

NCT01242943 | Terminated Phase 1

• 1 other identifier: PH-L19SIPI131-07/07
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 4

Brief Summary

The aim of this Study Protocol is to provide a basis for the clinical development of 131I-L19SIP as an anti-cancer therapeutic agent, following the promising results of a Phase I study.

Conditions

Patients With Cancer

Keywords

I131; L19; antibody; monoclonal; tumour targeting; radioimmunotherapy; cancer

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum tolerated dose (MTD)

  Establishment of the maximum tolerated dose (MTD) and the recommended dose (RD) for the radiolabelled L19SIP monoclonal antibody.

  4 weeks

• Phase II: Antitumour activity

  Investigation of the antitumour activity of 131I-L19SIP at the RD, in patients with advanced cancer.

  1- 14 months

Secondary Outcomes (5)

• Phase I: Study of the variation of radioactivity of 131I in whole blood, at several time intervals (Pharmacokinetics)

  2 days

• Phase II: Safety profile

  30 days/ administration

• Phase II: Overall Response Rate (ORR)

  6 and 12 months

• Phase II: Progression free survival (PFS)

  6 and 12 months

• Phase II: Survival rate

  6 and 12 months

Study Arms (1)

L19SIP I131

EXPERIMENTAL

Phase I: Multicentre, open-label, two-step single-arm dose escalation study in sequential cohorts of patients with cancer. Phase II: Prospective, open-label, single-arm, multicentre study of 131I-L19SIP, given at the RD as determined in phase I.

Drug: 131I-L19SIP Radioimmunotherapy (RIT)

Interventions

131I-L19SIP Radioimmunotherapy (RIT) DRUG

Dosimetric evaluation with 131I-L19SIP will be performed to assess eligibility for Radioimmunotherapy. Phase I: Patients eligible for Radioimmunotherapy will receive escalating doses of therapeutic 131I-L19SIP administration (intravenously) at the following dosages (expressed in mCi/m2): 111, 139 and 167.

L19SIP I131

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with cancer, with progressive disease in pre-study period, refractory to conventional standard treatments.
• Histologically/cytologically confirmed diagnosis of cancer, preferably lung cancer, prostate cancer and colorectal cancer (CRC). At least one measurable (minimum 2.0 cm), non irradiated lesion defined according to modified RECIST criteria, i.e. whenever the measurable disease is restricted to a solitary lesion, its neoplastic nature need not to be confirmed by cytology/histology.
• ECOG performance status grade 0 or 1.
• Age ≥18 and ≤ 75 years.
• Adequate haematological, liver and renal function (haemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1.50 x 10\^9/L; platelets ≥ 100 x 10\^9/L, bilirubin within UNL; alkaline phosphatase≤ 2.5 x UNL; ALT, AST ≤ UNL or ≤ 2.5 x UNL in case of liver metastases; albumin ≥ 2.5 g/dL; creatinine ≤ UNL.
• All acute toxic effects (excluding alopecia) of any prior therapy (including surgery radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v.3.0) Grade ≤ 1.
• Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment.
• If of childbearing potential, agreement to use adequate contraceptive methods (e.g. oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug.
• Evidence of a personally signed and dated IEC-approved Informed Consent indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study.
• Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
• Life expectancy of at least 3 months.
• Signed and dated informed consent.

You may not qualify if:

• Chemotherapy, radiation, hormonotherapy (with the exception of a gradual titration of LHRH agonists) or immunotherapy or participation in any investigational drug study within 4 weeks of study entry (6 weeks in case of prior nitroureas chemotherapy).
• Prior radiation dose \> 30% of bone marrow volume.
• Presence of cirrhosis or active hepatitis.
• Presence of serious cardiac (congestive heart failure, heart insufficiency \> grade II NYHA, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorders.
• Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
• Recovery from major trauma including surgery within 4 weeks of administration of study treatment.
• Pregnancy or lactation or unwillingness to use adequate method of birth control.
• Active infection or incomplete wound healing.
• Known history of allergy to intravenously administered proteins / peptides / antibodies.
• Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (4)

University Hospital Pisa

Pisa, Tuscany, 56126, Italy

Location

Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)

Meldola, Italy

Location

Irccs Ospedale Casa Sollievo Della Sofferenza - San Giovanni Rotondo

San Giovanni Rotondo (FG), Italy

Location

University College London, UCL Cancer Institute

London, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Giuliano Mariani, Prof

  University Hospital Pisa, Italy

  PRINCIPAL INVESTIGATOR

• Tim Meyer, Dr

  University College London (UCL) Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2010
• First Posted: November 17, 2010
• Study Start: November 1, 2008
• Primary Completion: February 1, 2011
• Study Completion: May 1, 2011
• Last Updated: November 22, 2011

Record last verified: 2011-11

Locations

IT (3); GB (1)