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

Sponsored by:	Sanofi-Aventis
Information provided by:	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT00791544

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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
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

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

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

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 ]

Estimated Enrollment:	54
Study Start Date:	November 2008
Estimated Study Completion Date:	April 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

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

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

Contacts

Contact: Public Registry ICD

GV-Contact-us@sanofi-aventis.com

Locations

France
Sanofi-aventis Administrative Office	Recruiting
Paris, France

Sponsors and Collaborators

Sanofi-Aventis

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:	sanofi-aventis ( ICD Study Director )
Study ID Numbers:	TED10630, EudraCT 2008-000809-10
Study First Received:	November 13, 2008
Last Updated:	May 29, 2009
ClinicalTrials.gov Identifier:	NCT00791544 History of Changes
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Sanofi-Aventis:

monoclonal antibody, anti IGF1R

Study placed in the following topic categories:

Erlotinib
Liver Diseases
Digestive System Neoplasms
Immunologic Factors
Carcinoma, Hepatocellular
Protein Kinase Inhibitors
Insulin
Carcinoma
Antibodies, Monoclonal
Liver Neoplasms

Signs and Symptoms
Antibodies
Digestive System Diseases
Gastrointestinal Neoplasms
Mitogens
Adenocarcinoma
Hepatocellular Carcinoma
Sorafenib
Immunoglobulins
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Erlotinib
Liver Diseases
Neoplasms by Histologic Type
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Carcinoma, Hepatocellular
Physiological Effects of Drugs
Enzyme Inhibitors
Protein Kinase Inhibitors

Pharmacologic Actions
Carcinoma
Liver Neoplasms
Antibodies, Monoclonal
Neoplasms
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Adenocarcinoma
Sorafenib
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 10, 2009