Epithelioid MesotheliomaPhase 2NCT01861301
Tivantinib in Treating Patients With Previously Treated Malignant Mesothelioma
A Phase 2 study testing Laboratory Biomarker Analysis and Tivantinib in people with Epithelioid Mesothelioma and Recurrent Malignant Mesothelioma, run by National Cancer Institute (NCI) at 18 sites in United States.
Trial summary
This phase II trial studies how well tivantinib works in treating patients with previously treated malignant mesothelioma. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epithelioid Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatoid Mesothelioma
- What is being tested?
- Laboratory Biomarker Analysis and Tivantinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 18 sitesUnited States
- Study dates
- Jan 2013to Mar 2015
- 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
- Patients must have histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma, epithelial, sarcomatoid, or mixed subtype; the patient's disease must be metastatic, recurrent, or unresectable
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; pleural effusions and ascites are not considered measurable lesions
- No more than two prior cytotoxic chemotherapy regimens; prior chemotherapy with pemetrexed is required; prior intrapleural cytotoxic agents (including bleomycin) are allowed, and are not counted as a cytotoxic chemotherapy; chemotherapy must have been completed at least 4 weeks prior; patients who have previously received radiation therapy are eligible provided that the only site of measurable disease is not located within the radiation therapy port; at least 4 weeks must have elapsed from completion of the radiation therapy and all signs of toxicity must have resolved
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- Life expectancy of greater than 3 months
- Hemoglobin >= 9.0 g/dL
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- White blood cells (WBC) >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 X institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Serum creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- The effects of ARQ 197 on the developing human fetus are unknown; for this reason and because tyrosine kinase inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ARQ 197 administration
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (to grade =< 1) due to agents administered more than 4 weeks earlier
- Patients who are receiving any other investigational agents
- Patients with known 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
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197
- ARQ 197 is metabolized by cytochrome P450 (CYP)2C19, and to a lesser extent CYP3A4; the metabolism and consequently overall pharmacokinetics of ARQ 197 could be altered by inhibitors and/or inducers or other substrates of CYP2C19 and CYP3A4; while inhibitors/inducers of these cytochrome P450 isoenzymes are not specifically excluded, investigators should be aware that ARQ 197 exposure may be altered by the concomitant administration of these drugs; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as >= grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring > 6 months prior to study entry is permitted)
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because ARQ 197 is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ARQ 197, breastfeeding should be discontinued if the mother is treated with ARQ 197
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ARQ197; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- No prior treatment with a c-MET inhibitor
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Northwestern University
Chicago, Illinois, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Decatur Memorial Hospital
Decatur, Illinois, 62526
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, 46845
Ingalls Memorial Hospital
Harvey, Illinois, 60426
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
City of Hope South Pasadena
South Pasadena, California, 91030
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
About this study
Official title: A Phase 2 Study of ARQ 197 in Patients With Previously-Treated Malignant Mesothelioma
This phase II trial studies how well tivantinib works in treating patients with previously treated malignant mesothelioma. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the objective response rate of patients with malignant mesothelioma who are treated with ARQ 197 (tivantinib).
SECONDARY OBJECTIVES:
- To determine the progression-free survival of patients with malignant mesothelioma who are treated with ARQ 197.
II. To determine the toxicity experienced by patients with malignant mesothelioma who are treated with ARQ 197.
III. To determine median and overall survival of patients with malignant mesothelioma who are treated with ARQ 197.
TERTIARY OBJECTIVES:
- To determine the frequency of mesenchymal-epithelial transition (MET) gene amplification in malignant mesothelioma patient tumor samples, and to correlate the results with MET immunohistochemistry (IHC).
II. To determine whether MET gene amplification results in increased sensitivity to ARQ 197 as observed by improved clinical outcomes (response rate [RR] and progression free survival [PFS]) compared to those without MET gene over-expression/amplification.
III. To determine whether high baseline serum hepatocyte growth factor (HGF), as well as changes in serum HGF during treatment at pre-defined early time points, correlate with treatment efficacy and clinical outcome, as measured by response rate and progression-free survival.
IV. To identify mutations by sequencing of specific areas of the MET gene in tumor samples (semaphorin [SEMA], jumonji [JM] and tyrosine kinase domains).
- To perform immunohistochemistry (IHC) of mesothelioma tumors for HGF, MET and phosphorylated (p)-MET (pY1003 and pY1230/34/35).
VI. To assess serum HGF and serum soluble MET levels by enzyme linked immunosorbent assay (ELISA) (R\&D systems) pre-treatment, after 2 cycles and at disease progression.
OUTLINE:
Patients receive tivantinib orally (PO) twice daily (BID). Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
- Conditions
- Epithelioid Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatoid Mesothelioma, Stage II Pleural Mesothelioma, Stage III Pleural Mesothelioma, Stage IV Pleural Mesothelioma
- Being tested
- Laboratory Biomarker Analysis, Tivantinib
- Medical subject headings
- Mesothelioma, Malignant, Solitary Fibrous Tumor, Pleural
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
TivantinibDrug
Also called ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tivantinib) | Experimental | Patients receive tivantinib 360 PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Tivantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Radiologic Response Rate (Complete or Partial Response) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 1 year
Secondary outcomes (3)
Incidence of Adverse Events, Graded Per NCI CTCAE Version 4
Grade 3 or higher AE of any type, regardless of attribution.
Measured: Up to 2 years
Overall Survival
Analyzed using the Kaplan-Meier method.
Measured: Up to 2 years
Progression-free Survival
Time to disease progression or death from any cause. Analyzed using the Kaplan-Meier method.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2013 (estimated)
- Study startJan 2013
- Primary completionMar 2015
- Study completionMar 2015
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 Epithelioid 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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Hedy Kindler, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01861301
- Sponsor's protocol ID
- NCI-2013-00937
- Other IDs
- NCI-2013-00937, 12-2158, 12-2158, 9267, N01CM00071, P30CA014599
- Status last verified
- Aug 2016
- First submitted
- 20 May 2013
- Last updated
- 24 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of ARQ 197 in Patients With Previously-Treated Malignant Mesothelioma
- ClinicalTrials.gov ID
- NCT01861301
- Acronym / sponsor ID
- NCI-2013-00937
- Conditions
- Epithelioid Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatoid Mesothelioma, Stage II Pleural Mesothelioma, Stage III Pleural Mesothelioma, Stage IV Pleural Mesothelioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 23 May 2013 (estimated)
- Results
- Posted 24 Oct 2016
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 studies how well tivantinib works in treating patients with previously treated malignant mesothelioma. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the objective response rate of patients with malignant mesothelioma who are treated with ARQ 197 (tivantinib).
SECONDARY OBJECTIVES:
- To determine the progression-free survival of patients with malignant mesothelioma who are treated with ARQ 197.
II. To determine the toxicity experienced by patients with malignant mesothelioma who are treated with ARQ 197.
III. To determine median and overall survival of patients with malignant mesothelioma who are treated with ARQ 197.
TERTIARY OBJECTIVES:
- To determine the frequency of mesenchymal-epithelial transition (MET) gene amplification in malignant mesothelioma patient tumor samples, and to correlate the results with MET immunohistochemistry (IHC).
II. To determine whether MET gene amplification results in increased sensitivity to ARQ 197 as observed by improved clinical outcomes (response rate [RR] and progression free survival [PFS]) compared to those without MET gene over-expression/amplification.
III. To determine whether high baseline serum hepatocyte growth factor (HGF), as well as changes in serum HGF during treatment at pre-defined early time points, correlate with treatment efficacy and clinical outcome, as measured by response rate and progression-free survival.
IV. To identify mutations by sequencing of specific areas of the MET gene in tumor samples (semaphorin [SEMA], jumonji [JM] and tyrosine kinase domains).
- To perform immunohistochemistry (IHC) of mesothelioma tumors for HGF, MET and phosphorylated (p)-MET (pY1003 and pY1230/34/35).
VI. To assess serum HGF and serum soluble MET levels by enzyme linked immunosorbent assay (ELISA) (R\&D systems) pre-treatment, after 2 cycles and at disease progression.
OUTLINE:
Patients receive tivantinib orally (PO) twice daily (BID). Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 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 (tivantinib) | Experimental | Other: Laboratory Biomarker Analysis, Drug: TivantinibPatients receive tivantinib 360 PO BID. 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 (14 listed)
- Patients must have histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma, epithelial, sarcomatoid, or mixed subtype; the patient's disease must be metastatic, recurrent, or unresectable
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; pleural effusions and ascites are not considered measurable lesions
- No more than two prior cytotoxic chemotherapy regimens; prior chemotherapy with pemetrexed is required; prior intrapleural cytotoxic agents (including bleomycin) are allowed, and are not counted as a cytotoxic chemotherapy; chemotherapy must have been completed at least 4 weeks prior; patients who have previously received radiation therapy are eligible provided that the only site of measurable disease is not located within the radiation therapy port; at least 4 weeks must have elapsed from completion of the radiation therapy and all signs of toxicity must have resolved
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- Life expectancy of greater than 3 months
Key exclusion criteria (10 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (to grade =< 1) due to agents administered more than 4 weeks earlier
- Patients who are receiving any other investigational agents
- Patients with known 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
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197
- ARQ 197 is metabolized by cytochrome P450 (CYP)2C19, and to a lesser extent CYP3A4; the metabolism and consequently overall pharmacokinetics of ARQ 197 could be altered by inhibitors and/or inducers or other substrates of CYP2C19 and CYP3A4; while inhibitors/inducers of these cytochrome P450 isoenzymes are not specifically excluded, investigators should be aware that ARQ 197 exposure may be altered by the concomitant administration of these drugs; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (tivantinib) |
| TivantinibAlso: ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197Given PO | Drug | Treatment (tivantinib) |
Primary outcome
Objective Radiologic Response Rate (Complete or Partial Response) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Up to 1 year
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
3 secondary outcomes
Incidence of Adverse Events, Graded Per NCI CTCAE Version 4
Time frame: Up to 2 years
Overall Survival
Time frame: Up to 2 years
Progression-free Survival
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Atezolizumab, Pemetrexed Disodium, Cisplatin, and Surgery With or Without Radiation Therapy in Treating Patients With Stage I-III Pleural Malignant Mesothelioma
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Induction Chemo+Immunotherapy in Resectable Epithelioid and Biphasic Pleural Mesothelioma (CHIMERA Study)
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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.
Hedy Kindler principal investigator
University of Chicago Comprehensive Cancer Center
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis and Tivantinib in people with Epithelioid Mesothelioma and Recurrent Malignant Mesothelioma, run by National Cancer Institute (NCI) at 18 sites 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 14 inclusion and 10 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 24 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites 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 24 Oct 2016). 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?
Objective Radiologic Response Rate (Complete or Partial Response) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (time frame: Up to 1 year). 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 24 Oct 2016.