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

Primary Purpose

Liver Carcinoma

Status

Terminated

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

AVE1642

sorafenib

erlotinib

About this trial

This is an interventional treatment trial for Liver Carcinoma focused on measuring monoclonal antibody, anti IGF1R

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Sanofi-Aventis Administrative Office

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

Dose Level -1

Dose Level 1

Dose Level 2

Dose Level 3

Dose Level 4

Dose Level 5

Combination cohort 1

Combination cohort 2

Arm Description

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

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

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

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

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

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

AVE1642 selected dose in combination with sorafenib

AVE1642 selected dose in combination with erlotinib

Outcomes

Primary Outcome Measures

Dose-limiting toxicities (DLT) based on grade = or > 3 hematological or non-hematological toxicity and on fasting hyperglycemia

Secondary Outcome Measures

Anti tumoral activity

Full Information

NCT ID

NCT00791544

First Posted

November 13, 2008

Last Updated

August 3, 2010

Sponsor

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT00791544

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2010

Overall Recruitment Status

Terminated

Why Stopped

Company decision to discontinue the AVE1642 development program, not due to any safety or efficacy concerns

Study Start Date

November 2008 (undefined)

Primary Completion Date

November 2009 (Actual)

Study Completion Date

November 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Sanofi

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Carcinoma

Keywords

monoclonal antibody, anti IGF1R

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Level -1

Arm Type

Experimental

Arm Description

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

Arm Title

Dose Level 1

Arm Type

Experimental

Arm Description

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

Arm Title

Dose Level 2

Arm Type

Experimental

Arm Description

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

Arm Title

Dose Level 3

Arm Type

Experimental

Arm Description

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

Arm Title

Dose Level 4

Arm Type

Experimental

Arm Description

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

Arm Title

Dose Level 5

Arm Type

Experimental

Arm Description

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

Arm Title

Combination cohort 1

Arm Type

Experimental

Arm Description

AVE1642 selected dose in combination with sorafenib

Arm Title

Combination cohort 2

Arm Type

Experimental

Arm Description

AVE1642 selected dose in combination with erlotinib

Intervention Type

Drug

Intervention Name(s)

AVE1642

Intervention Description

intravenous infusion

Intervention Type

Drug

Intervention Name(s)

sorafenib

Other Intervention Name(s)

Nevaxar

Intervention Description

oral intake

Intervention Type

Drug

Intervention Name(s)

erlotinib

Other Intervention Name(s)

Tarceva

Intervention Description

oral intake

Primary Outcome Measure Information:

Title

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)

Secondary Outcome Measure Information:

Title

Anti tumoral activity

Time Frame

Every 2 cycles

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Olivier Rosmorduc, Professor

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sanofi-Aventis Administrative Office

City

Paris

Country

France

12. IPD Sharing Statement

Learn more about this trial

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

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