Dose Finding Study of AVE1642 in Patients With Advanced or Metastatic Liver Carcinoma - Full Text View

Purpose

The primary objective of the study is to select the dose of AVE1642 to be administered in patients with liver carcinoma not eligible for local treatment.

The secondary objectives of the study are:

To evaluate the safety profile of AVE1642 as single agent and the safety profile of combinations with other anti-cancer therapies of interest in liver carcinoma , including detection of immunogenicity.
To evaluate pharmacokinetics and pharmacodynamics profiles of AVE1642 as single agent or any PK interactions when given in combination with other anti-cancer therapies.
To assess the preliminary clinical activity in terms of response rate (Complete response + Partial response), duration of responses, stabilisation rate and duration of stabilisation, according to RECIST criteria.
To assess the biological activity at the tumor level.

Condition	Intervention	Phase
Liver Carcinoma	Drug: AVE1642 Drug: sorafenib Drug: erlotinib	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Dose-finding, Safety, Pharmacokinetic and Pharmacodynamic Study of AVE1642, an Anti-Insulin-like Growth Factor-1 Receptor (IGF-1R/CD221) Monoclonal Antibody, Administered as Single Agent and in Combination With Other Anti Cancer Therapies (Sorafenib or Erlotinib) in Patients With Advanced Liver Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Diabetes Medicines

Drug Information available for: Insulin-like growth factor I Erlotinib hydrochloride Erlotinib Sorafenib Sorafenib tosylate Mecasermin rinfabate

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:

Dose-limiting toxicities (DLT) based on grade = or > 3 hematological or non-hematological toxicity and on fasting hyperglycemia [ Time Frame: Cycle 1 and cycle 2 (6 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Anti tumoral activity [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]

Enrollment:	13
Study Start Date:	November 2008
Study Completion Date:	November 2009
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dose Level -1 0.5 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2	Drug: AVE1642 intravenous infusion Drug: sorafenib oral intake Other Name: Nevaxar
Experimental: Dose Level 1 1 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2	Drug: AVE1642 intravenous infusion Drug: sorafenib oral intake Other Name: Nevaxar
Experimental: Dose Level 2 3 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2	Drug: AVE1642 intravenous infusion Drug: sorafenib oral intake Other Name: Nevaxar
Experimental: Dose Level 3 6 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2	Drug: AVE1642 intravenous infusion Drug: sorafenib oral intake Other Name: Nevaxar
Experimental: Dose Level 4 12 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2	Drug: AVE1642 intravenous infusion Drug: sorafenib oral intake Other Name: Nevaxar
Experimental: Dose Level 5 18 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2	Drug: AVE1642 intravenous infusion Drug: sorafenib oral intake Other Name: Nevaxar
Experimental: Combination cohort 1 AVE1642 selected dose in combination with sorafenib	Drug: AVE1642 intravenous infusion Drug: sorafenib oral intake Other Name: Nevaxar
Experimental: Combination cohort 2 AVE1642 selected dose in combination with erlotinib	Drug: AVE1642 intravenous infusion Drug: erlotinib oral intake Other Name: Tarceva

Detailed Description:

AVE1642 will be administered as an IV infusion on day 1 and then every 3 weeks for at least 2 infusions for evaluability requirements. Curative and / or prophylactic management of allergic reactions during infusion will be implemented when needed. The duration of the study for one patient will include a period for inclusion of up to 2 weeks, at least 2 cycles of treatment in dose escalation step (one cycle of AVE1642 alone and at least one cycle of AVE1642 in combination) and at least one cycle of the combination in the extension cohort, followed, when possible, by a minimum of 30-day follow-up after the last drug administration, in order to detect any potential immunogenicity. In the second step, the patients will continue treatment until disease progression, unacceptable toxicity or willingness to stop.

The expected enrolment period is 15 months with at least 30 day follow-up after the last patient treated.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients not eligible for surgical resection, liver transplantation, local ablation techniques or chemoembolisation and with histologically proven liver carcinoma whenever possible or combination of radiologically documented hypervascular liver tumour and α foeto protein level ≥ 400 ng/ml
Signed and dated approved patient informed consent form prior to enrollment into the study

Exclusion Criteria:

ECOG performance status > 2
Inadequate organ function:
- Neutrophils (ANC) < 1,500/mm3
- Hemoglobin < 10g/dl
- Platelets < 100,000/mm3
- Total bilirubin > 1.5 x ULN
- ASAT, ALAT > 3 x ULN
- Creatininemia > 1.5 x ULN (or ≥ 2.0 mg/dl)
- INR > 1.6
- Liver cirrhosis Child Pugh B or C (score > 6)
- HbA1C > 8%
No measurable or evaluable tumoral lesion
Patients not eligible for sorafenib therapy and for whom this therapy cannot be postponed by 3 weeks (during AVE1642 single treatment period) in dose escalation part
Prior exposure to an anti-IGF-1R class compound

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00791544

Locations

France
Sanofi-Aventis Administrative Office
Paris, France

Sponsors and Collaborators

Sanofi

Investigators

Principal Investigator:

Olivier Rosmorduc, Professor

Hôpital St Antoine, 184 rue du Faubourg St Antoine, 75012 Paris - France

More Information

No publications provided

Responsible Party:	ICD Study Director, sanofi-aventis
ClinicalTrials.gov Identifier:	NCT00791544 History of Changes
Other Study ID Numbers:	TED10630, EudraCT 2008-000809-10
Study First Received:	November 13, 2008
Last Updated:	August 3, 2010
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Sanofi:

monoclonal antibody, anti IGF1R

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

Antibodies, Monoclonal
Erlotinib
Sorafenib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013