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

NCT00791544 | Terminated Phase 1 DMC

• 2 other identifiers: TED10630EudraCT 2008-000809-10
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Liver Carcinoma

Keywords

monoclonal antibody, anti IGF1R

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (1)

• Anti tumoral activity

  Every 2 cycles

Study Arms (8)

Dose Level -1

EXPERIMENTAL

0.5 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2

Drug: AVE1642; Drug: sorafenib

Dose Level 1

EXPERIMENTAL

1 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2

Drug: AVE1642; Drug: sorafenib

Dose Level 2

EXPERIMENTAL

3 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2

Drug: AVE1642; Drug: sorafenib

Dose Level 3

EXPERIMENTAL

6 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2

Drug: AVE1642; Drug: sorafenib

Dose Level 4

EXPERIMENTAL

12 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2

Drug: AVE1642; Drug: sorafenib

Dose Level 5

EXPERIMENTAL

18 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2

Drug: AVE1642; Drug: sorafenib

Combination cohort 1

EXPERIMENTAL

AVE1642 selected dose in combination with sorafenib

Drug: AVE1642; Drug: sorafenib

Combination cohort 2

EXPERIMENTAL

AVE1642 selected dose in combination with erlotinib

Drug: AVE1642; Drug: erlotinib

Interventions

AVE1642 DRUG

intravenous infusion

Combination cohort 1; Combination cohort 2; Dose Level -1; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4; Dose Level 5

sorafenib DRUG

oral intake

Also known as: Nevaxar

Combination cohort 1; Dose Level -1; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4; Dose Level 5

erlotinib DRUG

oral intake

Also known as: Tarceva

Combination cohort 2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Sanofi-Aventis Administrative Office

Paris, France

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

AVE1642; Sorafenib; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Olivier Rosmorduc, Professor

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 13, 2008
• First Posted: November 14, 2008
• Study Start: November 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: August 4, 2010

Record last verified: 2010-08

Locations

FR (1)