Liver CarcinomaPhase 1/2NCT00791544
Dose Finding Study of AVE1642 in Patients With Advanced or Metastatic Liver Carcinoma
A Phase 1/2 study testing AVE1642, sorafenib and erlotinib in people with Liver Carcinoma, run by Sanofi at 1 site in France.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Carcinoma
- What is being tested?
- AVE1642, sorafenib and erlotinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2008to Nov 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this 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
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.
Read the 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.
- Conditions
- Liver Carcinoma
- Keywords
- monoclonal antibody, anti IGF1R
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVE1642Drug
intravenous infusion
sorafenibDrug
Also called Nevaxar
oral intake
erlotinibDrug
Also called Tarceva
oral intake
| Study group | Role | What they receive |
|---|---|---|
| Dose Level -1 | Experimental | 0.5 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 Receives: Drug: AVE1642; Drug: sorafenib |
| Dose Level 1 | Experimental | 1 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 Receives: Drug: AVE1642; Drug: sorafenib |
| Dose Level 2 | Experimental | 3 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 Receives: Drug: AVE1642; Drug: sorafenib |
| Dose Level 3 | Experimental | 6 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 Receives: Drug: AVE1642; Drug: sorafenib |
| Dose Level 4 | Experimental | 12 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 Receives: Drug: AVE1642; Drug: sorafenib |
| Dose Level 5 | Experimental | 18 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 Receives: Drug: AVE1642; Drug: sorafenib |
| Combination cohort 1 | Experimental | AVE1642 selected dose in combination with sorafenib Receives: Drug: AVE1642; Drug: sorafenib |
| Combination cohort 2 | Experimental | AVE1642 selected dose in combination with erlotinib Receives: Drug: AVE1642; Drug: erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicities (DLT) based on grade = or > 3 hematological or non-hematological toxicity and on fasting hyperglycemia
Measured: Cycle 1 and cycle 2 (6 weeks)
Secondary outcomes (1)
Anti tumoral activity
Measured: Every 2 cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionNov 2009
- Study completionNov 2009
Why it stopped: Company decision to discontinue the AVE1642 development program, not due to any safety or efficacy concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CarcinomaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Olivier Rosmorduc, Professor, Principal investigator, Hôpital St Antoine, 184 rue du Faubourg St Antoine, 75012 Paris - France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00791544
- Sponsor's protocol ID
- TED10630
- Other IDs
- EudraCT 2008-000809-10
- Status last verified
- Aug 2010
- First submitted
- 13 Nov 2008
- Last updated
- 4 Aug 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00791544
- Acronym / sponsor ID
- TED10630
- Conditions
- Liver Carcinoma
- Keywords
- monoclonal antibody, anti IGF1R
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision to discontinue the AVE1642 development program, not due to any safety or efficacy concerns
- Enrolment
- 13 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Nov 2008
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 14 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Dose Level -1 | Experimental | Drug: AVE1642, Drug: sorafenib0.5 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 |
| Dose Level 1 | Experimental | Drug: AVE1642, Drug: sorafenib1 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 |
| Dose Level 2 | Experimental | Drug: AVE1642, Drug: sorafenib3 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 |
| Dose Level 3 | Experimental | Drug: AVE1642, Drug: sorafenib6 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 |
| Dose Level 4 | Experimental | Drug: AVE1642, Drug: sorafenib12 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 |
| Dose Level 5 | Experimental | Drug: AVE1642, Drug: sorafenib18 mg/kg AVE1642 single agent at cycle 1 with sorafenib at cycle 2 |
| Combination cohort 1 | Experimental | Drug: AVE1642, Drug: sorafenibAVE1642 selected dose in combination with sorafenib |
| Combination cohort 2 | Experimental | Drug: AVE1642, Drug: erlotinibAVE1642 selected dose in combination with erlotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (15 listed)
- ECOG performance status > 2
- Inadequate organ function:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AVE1642intravenous infusion | Drug | Combination cohort 1, Combination cohort 2, Dose Level -1, Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4, Dose Level 5 |
| sorafenibAlso: Nevaxaroral intake | Drug | Combination cohort 1, Dose Level -1, Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4, Dose Level 5 |
| erlotinibAlso: Tarcevaoral intake | Drug | Combination cohort 2 |
Primary outcome
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)
1 secondary outcome
Anti tumoral activity
Time frame: Every 2 cycles
Results and safety
The study was stopped early (reason given: Company decision to discontinue the AVE1642 development program, not due to any safety or efficacy concerns). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier Rosmorduc, Professor principal investigator
Hôpital St Antoine, 184 rue du Faubourg St Antoine, 75012 Paris - France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AVE1642, sorafenib and erlotinib in people with Liver Carcinoma, run by Sanofi at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Company decision to discontinue the AVE1642 development program, not due to any safety or efficacy concerns). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2010.