Dose Finding Study of AVE1642 in Patients With Advanced or Metastatic Liver Carcinoma

Liver Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00791544
• Other study ID #: TED10630
• Secondary ID: EudraCT 2008-000
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: November 13, 2008
• Last updated: August 3, 2010
• Start date: November 2008
• Est. completion date: November 2009

Study information

• Verified date: August 2010
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 a 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Liver Carcinoma

Intervention

Drug:
• AVE1642
intravenous infusion
• sorafenib
oral intake
• erlotinib
oral intake

Locations

Country	Name	City	State
France	Sanofi-Aventis Administrative Office	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicities (DLT) based on grade = or > 3 hematological or non-hematological toxicity and on fasting hyperglycemia		Cycle 1 and cycle 2 (6 weeks)	Yes
Secondary	Anti tumoral activity		Every 2 cycles	No