Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Phase I: Prospective, open-label, dose escalation study.

Phase II: Prospective, single-arm, open-label study, equivalent to the stage 1 of the Simon two-stage phase II design.

Phase I: Sequential assignment of Patient cohorts to one of six dose levels of L19TNFa: 1.3, 2.6, 5.2, 7.8, 10.4, 13.0 µg/kg.

Phase II: The Recommended Dose (RD) of 13.0 µg/kg of L19TNFα determined in Phase I.

Schedule: Infusions of L19TNFα on days 1, 3 and 5 of each 21-day cycle. Patients may remain on treatment for a maximum of six 21-day cycles.

L19TNFa

Filippo De Braud, Dr.

The recombinant human fusion protein L19TNFα was created with the intention to overcome the systemic toxicity of TNFα by directly targeting it to tumor tissues. Tumor-targeted L19TNFα would result in high and sustained intralesional bioactive TNFα concentrations.

The primary purpose of this Phase I/II study is to define a safe and potentially active treatment regimen of L19TNFα as a monotherapy and to evaluate the antitumor activity of this regimen in relapsed metastatic colorectal cancer subjects, for whom standard treatment options are exhausted. L19TNFα is an investigational drug that specifically and effectively binds to ED-B, which is abundantly expressed in cancer tissue. Accordingly, treatment should result in a high and long-lasting intratumoral accumulation of biologically active rh-TNFα. Although combined therapies of TNFα with cytotoxic drugs (e.g. melphalan) seem to be strikingly more active against sarcoma and melanoma than with TNFα alone - at least for the ILP setting it seems possible that the repeated intratumoral delivery of TNFα via L19TNFα might produce additional biologic effects, such as the induction of an immunologic antitumor response or the sustained inhibition of tumor-associated angiogenesis (Lejeune, 2006), that potentially could benefit advanced cancer subjects.

L19TNFα in Patients With Advanced Solid Tumors

Phase I/II Study of the Tumor-targeting Human L19TNFα Monoclonal Antibody-cytokine Fusion Protein in Patients With Advanced Solid Tumors

Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of L19TNFα.

Investigation of the anti-cancer activity of L19TNFα as monotherapy as measured by the Objective Response Rate (ORR) at the end of cycle 2 in subjects with relapsed or refractory locally advanced or metastatic colorectal cancer not amenable to standard systemic therapy.

Investigation of early signs of anti-tumor activity of L19TNFα as measured by Objective Response Rate (ORR) at the end of cycle 2, median Progression-Free Survival (PFS) and median Overall Survival (OS).

InnoPharma Inc.

Eudax S.r.l.

Philogen S.p.A.

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Analgesics

Dacarbazine

Interleukin-2

Analgesics, Non-Narcotic

Cohorts of 3-6 patients will receive escalating doses of L19-IL2 until MTD is reached.

L19-IL2 will be administered on days 1, 8 \& 15 of each 21-day-cycle. Dacarbazine will be given at a fixed dose on day 1 of each 21-day cycle, 30 minutes after the end of the L19-IL2 infusion.

During the phase II part of this study, 60 patients with Stage IV M1a and M1b melanoma will be randomized in a 1:1 ratio: 30 patients assigned to Arm 1 will receive L19IL2 at the RD + DTIC at a fixed dose.

During the phase II part of this study, 60 patients with Stage IV M1a and M1b melanoma will be randomized in a 1:1 ratio: 30 patients assigned to Arm 2 will receive DTIC at a fixed dose as monotherapy.

During phase I part of the study, increasing dose of L19IL2 from one cohort to the next will be performed in steps of 160,000 IU/kg starting at 480,000 IU/kg (i.e., 0.48; 0.64; 0.80 MioIU/kg until MTD is reached).

L19IL2 - Ph I

L19IL2 at RD will be administered to Arm 1 patients during phase II part of the study.

L19IL2 at RD - Ph II

Dacarbazine: 1 hour intravenous infusion on day 1 of each 21-cycle at a dosage of 1000 mg/m2 (fixed dose).

DTIC

Claus Garbe, Prof. M.D.

Michele Maio, Dr.med.

A prospective, open-label, multi-center, Phase I/II study of L19IL2 in combination with Dacarbazine in patients with metastatic melanoma.

A prospective, open-label, multi-center, Phase I/II dose escalation study in which cohorts of 3-6 patients with metastatic melanoma will be assigned to receive escalating doses of L19-IL2 in combination with a fixed dose of Dacarbazine.

After definition of MTD and RD during the phase II part of this study, 60 patients with Stage IV M1a and M1b melanoma will be randomized in a 1:1 ratio to receive open label the combination treatment at the RD (Arm 1) or DTIC monotherapy (Arm 2).

A Phase I/II Dose Escalation Study of the Tumor-targeting Human L19-IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Dacarbazine for Patients With Metastatic Melanoma

Establish the MTD and the RD of L19IL2 (in combination with dacarbazine) to be used for phase II study

Safety evaluation including AEs, SAE and standard laboratory assessment

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Vinorelbine

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Cisplatin

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.

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

131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiotherapy (EBRT) and Concurrent Chemotherapy

Giovanni Paganelli, Dr

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.

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

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

The selective uptake of 131I-L19SIP or 124I-L19SIP in lung lesions and dosimetric analysis

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.

Dose limiting toxicities and maximum tolerated dose/recommended dose for the combination treatment

Intrapulmonal, extra pulmonal and overall response rate

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphosarcoma

Phase I: Multicentre, open-label, two-step singlearm dose escalation study in sequential cohorts of patients with cancer.

Phase II: Prospective, open-label, single-arm, multicentre study of 131I-F16SIP, given at the RD of 55.5 mCi/m2, as determined in phase I.

* Dosimetric evaluation with 131I-F16SIP or 124I-F16SIP will be performed to assess eligibility for Radioimmunotherapy.
* Patients eligible for Radioimmunotherapy will receive 55.5 mCi/m2 as established in the Phase I part of the study. A single dose of 5 to 10 mg of 131I-F16SIP will be administered intravenously (I.V).

131I-F16SIP Radioimmunotherapy (RIT)

Maddalena Sansovini, Dr

The aim of this Study Protocol is to provide a basis for the clinical development of 131I-F16SIP as an anti-cancer therapeutic agent.

The study follows and is greatly motivated by the promising results of a Phase I/II study with a similar investigational drug developed by our Company, 131I-L19SIP, in several Italian centers.

The F16SIP antibody is a fully human antibody, capable of preferential localization around tumour blood vessels while sparing normal tissues. The formation of new blood vessels is a rare event in the adult (exception made for the female reproductive cycle), but is a pathological feature of most aggressive types of cancer. The study aims at determining the therapeutic potential of the F16 antibody in SIP format,labelled with the radionuclide 131I, for the treatment of patients with different cancer types.

A Dose Finding and Efficacy Study of the Tumour Targeting Human 131I-F16SIP Monoclonal Antibody in Patients With Cancer

A Phase I/II Dose Finding and Efficacy Study of the Tumour Targeting Human 131I-F16SIP Monoclonal Antibody in Patients With Cancer

Establishment of the maximum tolerated dose (MTD), a recommended dose (RD) for the phase II part, and the safety of dosimetric and therapeutic administration of escalating dosages of the human radiolabeled antibody 131I-F16SIP.

Investigation of the antitumour activity of 131I-F16SIP at the RD.

Evaluation of the pharmacokinetics of 131I-F16SIP and 124I-F16SIP.

Determination of the overall safety profile of the iodinated antibody characterized by type, frequency, severity, timing and relationship to study therapy of adverse events and laboratory abnormalities in the first and eventual following administrations in all patients receiving a therapeutic dose.

Evaluation of the overall Response Rate (ORR) for all patients having received a therapeutic dose.

Evaluation of the progression free survival (PFS) for all patients having received a therapeutic dose.

Evaluation of the survival rate at 6 and 12 months and overall survival time for all patients having received a therapeutic dose.

Symptoms and General Pathology

Nervous System Diseases

Neoplasm Metastasis

Neoplasms, Second Primary

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT)

* Patients will be treated with WBRT administering a total dosage of 30 Gy in fractions of 3 Gy
* Dosimetric evaluation with 131I-L19SIP or 124I-L19SIP will be performed to assess eligibility for RIT.
* Patients eligible for RIT will receive a therapeutic dose of 131I-L19SIP.
* Total treatment duration is up to 4 weeks

Secondo Lastoria, Dr

Paul Mullholand, Dr

The aim of this Proof of Concept study is to determine the therapeutic potential of the L19SIP antibody, labeled with the radionuclide 131I in combination with external beam radiation, for the treatment of patients with multiple brain metastases 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 (exception made for the female reproductive cycle), but is a pathological feature in most aggressive types of cancer. The presented study follows a Phase I and a subsequent Phase I/II dose finding and efficacy study with the same agent in patients with a variety of cancers where 131I-L19SIP had shown an excellent tolerability and therapeutic benefit for some patients enrolled in the study.

131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiation in Patients With Multiple Brain Metastases From Solid Tumors

A Prospective Non-randomized Study of 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT) in Patients With Multiple Brain Metastases From Solid Tumors

Selective uptake of 131I-L19SIP or 124I-L19SIP in brain lesions

Safety will be assessed through physical examinations, vital signs, laboratory tests (including serum chemistries, hematology parameters) and the recording of adverse events. Treatment emergent adverse events will be summarized by CTCAE version 3 (and if possible by the RTOG/EORTG scale) and worse grade for all treated patients. Laboratory values and change in vital signs will be summarized.

Intracranial, extra cranial and overall response

GPA score will be assessed at the screening visit, during treatment and follow-up.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
L19TNFα in Patients With Advanced Solid Tumors	NCT01253837	Solid Tumors Colorectal Canc...	L19TNFa	18 Years -	Philogen S.p.A.
A Phase I/II Dose Escalation Study of the Tumor-targeting Human L19-IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Dacarbazine for Patients With Metastatic Melanoma	NCT02076646	Metastatic Mela...	L19IL2 - Ph I L19IL2 at RD - ... DTIC	18 Years - 70 Years	Philogen S.p.A.
131I-L19SIP Radioimmunotherapy Combined With Radiochemotherapy in Patients With Locally-advanced Non Small Cell Lung Cancer (NSCLC)	NCT01124812	Non Small Cell ...	131I-L19SIP Rad...	18 Years -	Philogen S.p.A.
A Phase I/II Dose Escalation Study of the Tumor-targeting Human L19-IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Dacarbazine for Patients With Metastatic Melanoma	NCT02076646	Metastatic Mela...	L19IL2 - Ph I L19IL2 at RD - ... DTIC	18 Years - 70 Years	Philogen S.p.A.
A Dose Finding and Efficacy Study of the Tumour Targeting Human 131I-F16SIP Monoclonal Antibody in Patients With Cancer	NCT01240720	Cancer	131I-F16SIP Rad...	18 Years -	Philogen S.p.A.
131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiation in Patients With Multiple Brain Metastases From Solid Tumors	NCT01125085	Brain Metastase...	131I-L19SIP Rad...	18 Years -	Philogen S.p.A.

Spots Global Cancer Trial Database for tumor targeting