Pleural MesotheliomaPhase 2NCT01160458
Phase II Study of IMC-A12 in Patients With Mesothelioma Who Have Been Previously Treated With Chemotherapy
A Phase 2 study testing IMC-A12 in people with Pleural Mesothelioma and Peritoneal Mesothelioma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Background: IMC-A12, a new cancer treatment that has not yet been approved by the U.S. Food and Drug Administration, is an antibody that is designed to block the effects of a protein called Type I Insulin-Like Growth Factor (IGF-1R). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pleural Mesothelioma, Peritoneal Mesothelioma
- What is being tested?
- IMC-A12
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2010to 24 Feb 2017
- 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
- Both men and women and members of all races and ethnic groups are eligible for this trial. Every effort will be made to recruit women and minorities in this study.
Who cannot join
- Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the principal investigator.
- Patients with poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided their blood glucose is below 160 mg/dL when fasting and if they are on a stable dietary or therapeutic regimen for this condition with their HbA1C of less than 7%.
- Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Human immunodeficiency virus (HIV) positive patients with poorly controlled viral loads (viral load > 50 copies HIV/ml), and/or acquired immune deficiency syndrome (AIDS)-defining illnesses will be excluded due to the possibility that IMC-A12 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to IMC-A12. HIV positive patients with mesothelioma not meeting the above criteria can be considered for inclusion in the study.
- Patients may not be receiving any other investigational agents.
- History of another invasive malignancy in the last five years. Adequately treated non-invasive, non-melanoma skin cancers as well as in situ carcinoma of the cervix will be allowed.
Show all 11Show fewer
- Prior treatment with drugs of the IGF-1R inhibitor class.
- Patients with tumor amenable to potentially curative therapy as assessed by the investigator. In patients with peritoneal mesothelioma who have had no prior surgery, a surgical consultation will be obtained to see if the patient is a candidate for debulking surgery.
- Pregnant women are excluded from this study because IMC-A12 is a monoclonal antibody to IGF-1R with the potential for teratogenic or abortifacient effects. Immunoglobulin G (IgG) antibody may also potentially be secreted in milk and therefore breastfeeding women should be excluded. Because of the potential of teratogenic or abortifacient effects women of childbearing potential and men must agree to use adequate contraception (barrier methods) before, during the study and for a period of 3 months after the last dose of the investigational agent.
- Patients must not be on hormonal forms of birth control or hormone replacement therapy, as this may affect the study drug. Patients must be off hormonal forms of birth control or hormone replacement therapy for at least 4 weeks prior to initiating the study.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to IMC-A12.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
Background:
Read more
- IMC-A12, a new cancer treatment that has not yet been approved by the U.S. Food and Drug Administration, is an antibody that is designed to block the effects of a protein called Type I Insulin-Like Growth Factor (IGF-1R). IMC-A12 blocks the receptors in cells that respond to IGF-1R, which are thought to play an important role in helping cancer cells to grow and divide. Researchers are interested in determining whether IMC-A12 is an effective treatment for individuals who have mesothelioma that has not responded to standard chemotherapy.
Objectives:
- To evaluate the safety and effectiveness of IMC-A12 treatment in individuals with mesothelioma who have previously had chemotherapy.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with mesothelioma that has not responded to chemotherapy.
Design:
- Eligible participants will be screened with a full physical examination and medical history, blood and urine samples, and imaging studies.
- Participants will receive IMC-A12 once every 3 weeks (21-day cycle), and will be evaluated before the start of each new cycle with blood tests and imaging studies if needed.
- Treatment cycles will continue for as long as needed, unless severe side effects develop or the disease progresses.
Read the detailed description
Background:
Platinum-based chemotherapy is the standard of care for advanced unresectable malignant mesothelioma. New options for treatment are necessary in patients with advanced disease that have progressed on platinum-based therapy. The insulin-like growth factor (IGF) pathway is being studies in various malignancies including mesothelioma. IMC-A12 is an anti-IGF-1R monoclonal antibody that has shown activity in patients with various malignancies.
Objectives:
Primary Objective:
- To determine the clinical response rate (partial response (PR)+complete response (CR)) to IMC-A12 monotherapy in patients with advanced mesothelioma.
Secondary Objectives:
- To determine response duration, progression free survival (PFS) and overall survival (OS).
- To assess safety of IMC-A12 in patients with mesothelioma
Exploratory Objectives:
- To evaluate tumor IGF-1R expression and correlation with response
- To correlate response to therapy with changes in fludeoxyglucose 18F-positron emission tomography (FDG-PET) imaging.
- To monitor serum mesothelin and cancer antigen 125 or carbohydrate antigen 125 (CA-125) levels prior to and during therapy.
Eligibility:
- Patients with histologically confirmed malignant pleural or peritoneal mesothelioma who have previously been treated on at least one platinum-containing chemotherapy regimen with progressive disease documented prior to study entry, or have refused cytotoxic chemotherapy.
- Measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for pleural mesothelioma or by RECIST criteria for peritoneal mesothelioma.
- Adequate renal, hepatic and hematopoietic function.
- No major surgery, radiotherapy, chemotherapy or biologic therapy within 28 days of IMC-A12 therapy
Design:
- Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks.
- Treatment with IMC-A12 alone will continue until disease progression.
- Toxicity will be assessed every cycle by the Cancer Therapy Evaluation Program (CTEP) Version 4.0 of Common Terminology Criteria for Adverse Events (CTCAE).
- Tumor response assessments will be performed every 2 cycles.
- Conditions
- Pleural Mesothelioma, Peritoneal Mesothelioma
- Being tested
- IMC-A12
- Keywords
- Monoclonal Antibody, Pleural Mesothelioma, Peritoneal Mesothelioma
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMC-A12Drug
Also called A12 Cixutumumab
20 mg/kg intravenous over 60 minutes or not to exceed 25 mg/minute once every 3 weeks (+ or -1 day cycle 3 and beyond)
| Study group | Role | What they receive |
|---|---|---|
| IMC-A12 Monotherapy in Patients | Experimental | 20 mg/kg intravenous over 60 minutes or not to exceed 25 mg/minute once every 3 weeks (+ or -1 day cycle 3 and beyond) Receives: Drug: IMC-A12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response Rate (PR+CR)
Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is complete disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Measured: 36 months
Secondary outcomes (4)
Safety of IMC-A12 in Patients With Mesothelioma
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Measured: Date treatment consent signed to date off study, approximately 36 months
Duration of Overall Response
Duration of Overall Response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Complete response is complete disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease is at least a 20% increase in the sum of the longest diameter of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progression).
Measured: 36 months
Progression Free Survival (PFS)
Progression Free Survival is defined as the time interval from the start of treatment to documented evidence of disease progression. Progressive disease is at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study longest diameter (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progression).
Measured: To study completion, an average of 3 years
Overall Survival (OS)
Overall survival is the time interval from the start of treatment to the date of death.
Measured: To study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2010 (estimated)
- Study start2 Jun 2010
- Primary completion13 Aug 2016
- Study completion24 Feb 2017
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pleural MesotheliomaStudies 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Raffit Hassan, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Raffit Hassan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01160458
- Sponsor's protocol ID
- 100146
- Other IDs
- 10-C-0146
- Status last verified
- Mar 2018
- First submitted
- 9 Jul 2010
- Last updated
- 10 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bridda A, Padoan I, Mencarelli R, Frego M. Peritoneal mesothelioma: a review. MedGenMed. 2007 May 10;9(2):32.
PubMed 17955087Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/JCO.2003.11.136.
PubMed 12860938O'Byrne KJ, Edwards JG, Waller DA. Clinico-pathological and biological prognostic factors in pleural malignant mesothelioma. Lung Cancer. 2004 Aug;45 Suppl 1:S45-8. doi: 10.1016/j.lungcan.2004.04.025.
PubMed 15261433
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of IMC-A12 in Patients With Mesothelioma Who Have Been Previously Treated With Chemotherapy
- ClinicalTrials.gov ID
- NCT01160458
- Acronym / sponsor ID
- 100146
- Conditions
- Pleural Mesothelioma, Peritoneal Mesothelioma
- Keywords
- Monoclonal Antibody, Pleural Mesothelioma, Peritoneal Mesothelioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 2 Jun 2010 (actual)
- Primary completion
- 13 Aug 2016 (actual)
- Study completion
- 24 Feb 2017 (actual)
- First posted
- 12 Jul 2010 (estimated)
- Results
- Posted 14 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Background:
- IMC-A12, a new cancer treatment that has not yet been approved by the U.S. Food and Drug Administration, is an antibody that is designed to block the effects of a protein called Type I Insulin-Like Growth Factor (IGF-1R). IMC-A12 blocks the receptors in cells that respond to IGF-1R, which are thought to play an important role in helping cancer cells to grow and divide. Researchers are interested in determining whether IMC-A12 is an effective treatment for individuals who have mesothelioma that has not responded to standard chemotherapy.
Objectives:
- To evaluate the safety and effectiveness of IMC-A12 treatment in individuals with mesothelioma who have previously had chemotherapy.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with mesothelioma that has not responded to chemotherapy.
Design:
- Eligible participants will be screened with a full physical examination and medical history, blood and urine samples, and imaging studies.
- Participants will receive IMC-A12 once every 3 weeks (21-day cycle), and will be evaluated before the start of each new cycle with blood tests and imaging studies if needed.
- Treatment cycles will continue for as long as needed, unless severe side effects develop or the disease progresses.
Detailed description
Background:
Platinum-based chemotherapy is the standard of care for advanced unresectable malignant mesothelioma. New options for treatment are necessary in patients with advanced disease that have progressed on platinum-based therapy. The insulin-like growth factor (IGF) pathway is being studies in various malignancies including mesothelioma. IMC-A12 is an anti-IGF-1R monoclonal antibody that has shown activity in patients with various malignancies.
Objectives:
Primary Objective:
- To determine the clinical response rate (partial response (PR)+complete response (CR)) to IMC-A12 monotherapy in patients with advanced mesothelioma.
Secondary Objectives:
- To determine response duration, progression free survival (PFS) and overall survival (OS).
- To assess safety of IMC-A12 in patients with mesothelioma
Exploratory Objectives:
- To evaluate tumor IGF-1R expression and correlation with response
- To correlate response to therapy with changes in fludeoxyglucose 18F-positron emission tomography (FDG-PET) imaging.
- To monitor serum mesothelin and cancer antigen 125 or carbohydrate antigen 125 (CA-125) levels prior to and during therapy.
Eligibility:
- Patients with histologically confirmed malignant pleural or peritoneal mesothelioma who have previously been treated on at least one platinum-containing chemotherapy regimen with progressive disease documented prior to study entry, or have refused cytotoxic chemotherapy.
- Measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for pleural mesothelioma or by RECIST criteria for peritoneal mesothelioma.
- Adequate renal, hepatic and hematopoietic function.
- No major surgery, radiotherapy, chemotherapy or biologic therapy within 28 days of IMC-A12 therapy
Design:
- Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks.
- Treatment with IMC-A12 alone will continue until disease progression.
- Toxicity will be assessed every cycle by the Cancer Therapy Evaluation Program (CTEP) Version 4.0 of Common Terminology Criteria for Adverse Events (CTCAE).
- Tumor response assessments will be performed every 2 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IMC-A12 Monotherapy in Patients | Experimental | Drug: IMC-A1220 mg/kg intravenous over 60 minutes or not to exceed 25 mg/minute once every 3 weeks (+ or -1 day cycle 3 and beyond) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Both men and women and members of all races and ethnic groups are eligible for this trial. Every effort will be made to recruit women and minorities in this study.
Key exclusion criteria (11 listed)
- Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the principal investigator.
- Patients with poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided their blood glucose is below 160 mg/dL when fasting and if they are on a stable dietary or therapeutic regimen for this condition with their HbA1C of less than 7%.
- Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Human immunodeficiency virus (HIV) positive patients with poorly controlled viral loads (viral load > 50 copies HIV/ml), and/or acquired immune deficiency syndrome (AIDS)-defining illnesses will be excluded due to the possibility that IMC-A12 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to IMC-A12. HIV positive patients with mesothelioma not meeting the above criteria can be considered for inclusion in the study.
- Patients may not be receiving any other investigational agents.
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 |
|---|---|---|
| IMC-A12Also: A12 Cixutumumab20 mg/kg intravenous over 60 minutes or not to exceed 25 mg/minute once every 3 weeks (+ or -1 day cycle 3 and beyond) | Drug | IMC-A12 Monotherapy in Patients |
Primary outcome
Clinical Response Rate (PR+CR)
Time frame: 36 months
Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is complete disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
4 secondary outcomes
Safety of IMC-A12 in Patients With Mesothelioma
Time frame: Date treatment consent signed to date off study, approximately 36 months
Duration of Overall Response
Time frame: 36 months
Progression Free Survival (PFS)
Time frame: To study completion, an average of 3 years
Overall Survival (OS)
Time frame: To study completion, an average of 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17955087Bridda A, Padoan I, Mencarelli R, Frego M. Peritoneal mesothelioma: a review. MedGenMed. 2007 May 10;9(2):32.
- Background: PubMed 12860938Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/JCO.2003.11.136.
- Background: PubMed 15261433O'Byrne KJ, Edwards JG, Waller DA. Clinico-pathological and biological prognostic factors in pleural malignant mesothelioma. Lung Cancer. 2004 Aug;45 Suppl 1:S45-8. doi: 10.1016/j.lungcan.2004.04.025.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Raffit Hassan, M.D. principal investigator
National Cancer Institute (NCI)
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 IMC-A12 in people with Pleural Mesothelioma and Peritoneal Mesothelioma, 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 1 inclusion and 11 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 10 Apr 2018. 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 14 May 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?
Clinical Response Rate (PR+CR) (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01160458, which also lists 3 linked publications.
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 10 Apr 2018; AzTrials last refreshed its copy on 7 Nov 2026.