Adult Primary Hepatocellular CarcinomaPhase 2NCT00639509
IMC-A12 in Treating Patients With Advanced Liver Cancer
A Phase 2 study testing cixutumumab, computed tomography and contrast-enhanced magnetic resonance imaging in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well IMC-A12 works in treating patients with advanced liver cancer. Monoclonal antibodies, such as IMC-A12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer
- What is being tested?
- cixutumumab, computed tomography and contrast-enhanced magnetic resonance imaging
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Feb 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically or cytologically confirmed hepatocellular carcinoma
- Unresectable, locally advanced, or metastatic disease
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- Child's Pugh score A5, A6, B7, or B8
- No known brain metastases
- No history of primary CNS tumors
Show all 42Show fewer
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Life expectancy > 3 months
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 75,000/mcL
- Total bilirubin ≤ 2 times upper limit of normal (ULN)
- AST/ALT ≤ 2.5 times ULN
- PT/INR ≤ 1.7 times ULN
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
- Fasting serum glucose ≤ 125 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No clinical encephalopathy
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12
- No poorly controlled diabetes mellitus
- Patients with a history of diabetes mellitus are eligible provided their blood glucose is within normal range (fasting blood glucose < 120 mg/dL OR below ULN) and patient is on a stable dietary or therapeutic regimen for this condition
- No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would preclude compliance with study requirements
- No history of seizures not well controlled with standard medical therapy
- No history of stroke
- No history of another primary cancer except for the following:
- Curatively resected nonmelanoma skin cancer
- Curatively treated carcinoma in situ of the cervix
- Other primary solid tumor with no known active disease present that in the opinion of the investigator would not affect treatment outcome
- Prior local therapy (i.e., surgery, radiotherapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) allowed provided the target lesion has not been treated with local therapy and/or the target lesion within the field of local therapy has shown an increase of ≥ 25% in size
- At least 4 weeks since prior local therapy
- No prior systemic therapy except for sorafenib tosylate
- No prior agents targeting the IGF or IGF-1R pathway
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No concurrent anticancer therapy
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase 2 Study of IMC-A12 (NSC742460) in Hepatocellular Carcinoma
This phase II trial is studying how well IMC-A12 works in treating patients with advanced liver cancer. Monoclonal antibodies, such as IMC-A12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the progression-free survival (PFS) at 4 months in patients with advanced hepatocellular carcinoma (HCC) treated with anti-IGF-1R recombinant monoclonal antibody IMC-A12.
II. To determine the best overall response rate in patients treated with this drug.
SECONDARY OBJECTIVES:
- To determine the median overall survival of patients treated with this drug. II. To evaluate the safety, tolerability, and adverse events profile of this drug in these patients.
III. To perform a subgroup analysis to compare PFS of patients with advanced HCC who are hepatitis B positive/hepatitis C negative versus patients who are hepatitis B negative/hepatitis C positive treated with this drug.
IV. To store pre-therapy paraffin embedded tumor tissue for future tissue-based correlative studies.
- To evaluate tumor necrotic areas using a new volumetric method of assessing non-viable tumor as a correlate for response.
VI. To prospectively validate and compare the CLIP and the GDETCH staging systems and additional prognostic factors.
OUTLINE: Patients receive anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients undergo serum sample collection at baseline for future tissue-based correlative studies. Previously collected paraffin embedded tumor tissue samples are also stored for future correlative studies.
After completion of study treatment, patients are followed every 3 months for at least 1 year.
- Conditions
- Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer
- Being tested
- cixutumumab, computed tomography, contrast-enhanced magnetic resonance imaging
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cixutumumabBiological
Also called anti-IGF-1R recombinant monoclonal antibody IMC-A12, IMC-A12
Given IV
computed tomographyProcedure or surgery
Also called tomography, computed
Undergo contrast-enhanced computed tomography
contrast-enhanced magnetic resonance imagingProcedure or surgery
Also called Contrast-enhanced MRI
Undergo contrast-enhanced magnetic resonance imaging
| Study group | Role | What they receive |
|---|---|---|
| Treatment (monoclonal antibody therapy) | Experimental | Patients receive anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity. Receives: Biological: cixutumumab; Procedure: computed tomography; Procedure: contrast-enhanced magnetic resonance imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS Rate
PFS defined as the time from first date of first treatment on the study until such time as progressive disease is confirmed or upon patient death if disease progression has not been evident at that time. A Simon's optimal two stage design will be used with the following assumption: a 4 months PFS of 62% is considered acceptable while a 4 months PFS of 42% is not acceptable.
Measured: At 4 months
Best Overall Response Rate (ORR)
Best overall ORR will be defined as the proportion of patients achieving either confirmed partial response (PR) or confirmed complete response (CR). A Simon's optimal two stage design will be used with the following assumption: ORR of more than 20% is acceptable and an ORR less than 5% is not acceptable.
Measured: From the start of the treatment until disease progression/recurrence
Secondary outcomes (1)
Median Overall Survival
Median Overall Survival
Measured: Post-Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2008 (estimated)
- Study startMar 2008
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Primary Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ghassan Abou-Alfa, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00639509
- Sponsor's protocol ID
- NCI-2009-00283
- Other IDs
- NCI-2009-00283, MSKCC-08015, CDR0000589633, 08-015, 8124, P30CA008748, N01CM62206
- Status last verified
- Mar 2012
- First submitted
- 19 Mar 2008
- Last updated
- 23 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of IMC-A12 (NSC742460) in Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT00639509
- Acronym / sponsor ID
- NCI-2009-00283
- Conditions
- Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Mar 2008
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 20 Mar 2008 (estimated)
- Results
- Posted 3 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well IMC-A12 works in treating patients with advanced liver cancer. Monoclonal antibodies, such as IMC-A12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
Detailed description
PRIMARY OBJECTIVES:
- To determine the progression-free survival (PFS) at 4 months in patients with advanced hepatocellular carcinoma (HCC) treated with anti-IGF-1R recombinant monoclonal antibody IMC-A12.
II. To determine the best overall response rate in patients treated with this drug.
SECONDARY OBJECTIVES:
- To determine the median overall survival of patients treated with this drug. II. To evaluate the safety, tolerability, and adverse events profile of this drug in these patients.
III. To perform a subgroup analysis to compare PFS of patients with advanced HCC who are hepatitis B positive/hepatitis C negative versus patients who are hepatitis B negative/hepatitis C positive treated with this drug.
IV. To store pre-therapy paraffin embedded tumor tissue for future tissue-based correlative studies.
- To evaluate tumor necrotic areas using a new volumetric method of assessing non-viable tumor as a correlate for response.
VI. To prospectively validate and compare the CLIP and the GDETCH staging systems and additional prognostic factors.
OUTLINE: Patients receive anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients undergo serum sample collection at baseline for future tissue-based correlative studies. Previously collected paraffin embedded tumor tissue samples are also stored for future correlative studies.
After completion of study treatment, patients are followed every 3 months for at least 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (monoclonal antibody therapy) | Experimental | Biological: cixutumumab, Procedure: computed tomography, Procedure: contrast-enhanced magnetic resonance imagingPatients receive anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (42 listed)
- Histologically or cytologically confirmed hepatocellular carcinoma
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- Child's Pugh score A5, A6, B7, or B8
- No known brain metastases
- No history of primary CNS tumors
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| cixutumumabAlso: anti-IGF-1R recombinant monoclonal antibody IMC-A12, IMC-A12Given IV | Biological | Treatment (monoclonal antibody therapy) |
| computed tomographyAlso: tomography, computedUndergo contrast-enhanced computed tomography | Procedure or surgery | Treatment (monoclonal antibody therapy) |
| contrast-enhanced magnetic resonance imagingAlso: Contrast-enhanced MRIUndergo contrast-enhanced magnetic resonance imaging | Procedure or surgery | Treatment (monoclonal antibody therapy) |
Primary outcome
PFS Rate
Time frame: At 4 months
PFS defined as the time from first date of first treatment on the study until such time as progressive disease is confirmed or upon patient death if disease progression has not been evident at that time. A Simon's optimal two stage design will be used with the following assumption: a 4 months PFS of 62% is considered acceptable while a 4 months PFS of 42% is not acceptable.
Best Overall Response Rate (ORR)
Time frame: From the start of the treatment until disease progression/recurrence
Best overall ORR will be defined as the proportion of patients achieving either confirmed partial response (PR) or confirmed complete response (CR). A Simon's optimal two stage design will be used with the following assumption: ORR of more than 20% is acceptable and an ORR less than 5% is not acceptable.
1 secondary outcome
Median Overall Survival
Time frame: Post-Treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ghassan Abou-Alfa principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cixutumumab, computed tomography and contrast-enhanced magnetic resonance imaging in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
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 42 inclusion and 0 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: finished, as of the sponsor's last update on 23 May 2014. 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 United States. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 3 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
PFS Rate (time frame: At 4 months). The study lists 2 primary outcomes in all. 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 23 May 2014.