Childhood Solid NeoplasmPhase 1NCT01725191
Tivantinib in Treating Younger Patients With Relapsed or Refractory Solid Tumors
A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Tivantinib in people with Childhood Solid Neoplasm, run by National Cancer Institute (NCI) at 20 sites in 2 countries.
Trial summary
This phase I trial studies the side effects and best dose of tivantinib in treating younger patients with solid tumors that have returned after a period of improvement or have not responded to treatment. 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 13 months to 21 years
- Conditions the study is for
- Childhood Solid Neoplasm
- What is being tested?
- Laboratory Biomarker Analysis, Pharmacological Study and Tivantinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 20 sitesin 2 countries
- Study dates
- Oct 2012to May 2015
- Phase
- Phase 1
- 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 13 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- PART A: Patients on dose levels -1 or 1 must have a body surface area (BSA) >= 0.65 m^2 at the time of study enrollment; patients on dose levels 2 or 3 must have a BSA >= 0.45 m^2 at the time of study enrollment
- PART B: There is no minimum body surface area requirement for patients in part B
- Patients with relapsed or refractory solid tumors including central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
- Patients must have either measurable or evaluable disease
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; note: neurologic deficits in patients with CNS tumors must have been stable or improving for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
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- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy:
- Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
- Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
- Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
- Radiation therapy (XRT): At least 14 days after local palliative XRT (small port); at least 150 days must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
- Stem cell infusion without TBI: No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant or stem cell infusion
- Patients may not have received prior therapy with tivantinib
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- Patients with known bone marrow involvement will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity; at least 5 of every cohort of 6 patients with a solid tumor must be evaluable for hematologic toxicity for the dose escalation part of the study; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- 1 to < 2 years: 0.6 mg/dL
- 2 to < 6 years: 0.8 mg/dL
- 6 to < 10 years: 1.0 mg/dL
- 10 to < 13 years: 1.2 mg/dL
- 13 to < 16 years: 1.5 mg/dL (males); 1.4 mg/dL (females)
- >= 16 years: 1.7 mg/dL (males); 1.4 mg/dL (females)
- Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
- Serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
- Serum albumin >= 2 g/dL
- All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
- Tissue blocks or slides must be sent; if tissue blocks or slides are unavailable, the study chair must be notified prior to enrollment
Who cannot join
- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are currently receiving other anti-cancer agents are not eligible
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
- Patients must not be receiving any of the following for at least 24 hours prior to enrollment: omeprazole, esoprazole, lansoprazole, pantoprazole, rifampin, omeprazole, fluvoxamine, or moclobemide
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- Patients must not be receiving any of the following for at least 24 hours prior to enrollment: atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John's Wort
- Nasogastric or G tube administration is not allowed; patients in part A must be able to swallow capsules
- Patients who have an uncontrolled infection are not eligible
- Patients who have received a prior solid organ transplantation are not eligible
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
- Patients with >= grade 2 bradycardia or with a known history >= grade 2 cardiac arrhythmia are not eligible
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
United States19 sites
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Baylor College of Medicine
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455
Columbia University Medical Center
New York, New York, 10032
Childrens Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Oregon Health and Science University
Portland, Oregon, 97239
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase 1 Study of the c-Met Inhibitor, Tivantinib (ARQ 197) in Children With Relapsed or Refractory Solid Tumors
This phase I trial studies the side effects and best dose of tivantinib in treating younger patients with solid tumors that have returned after a period of improvement or have not responded to treatment. 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 estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of tivantinib administered orally twice daily to children with refractory solid tumors.
II. To define and describe the toxicities of tivantinib administered on this schedule.
III. To characterize the pharmacokinetics of tivantinib (capsule as well as powder formulation) in children with refractory cancer.
SECONDARY OBJECTIVES:
- To preliminarily define the antitumor activity of tivantinib within the confines of a phase 1 study.
II. To preliminarily investigate whether cytochrome P450 (CYP450) polymorphisms impact pharmacokinetics or toxicity of tivantinib.
III. To preliminarily investigate whether tumor c-Met and/or hepatocyte growth factor (HGF) expression or downstream c-Met signaling correlate with clinical response to tivantinib.
OUTLINE: This is a dose-escalation study.
Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
- Conditions
- Childhood Solid Neoplasm
- Being tested
- Laboratory Biomarker Analysis, Pharmacological Study, Tivantinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
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 PO BID on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Tivantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: 28 days
Pharmacokinetic (PK) parameters of tivantinib
The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
Measured: Pre-dose, 1, 2, 4, 6 and 8-12 hours day 1 of course 1; pre-dose day 1 of course 2
Secondary outcomes (1)
Disease response assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Will be reported descriptively.
Measured: Up to 30 days after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2012 (estimated)
- Study startOct 2012
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood Solid NeoplasmStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- James Geller, Principal investigator, COG Phase I Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01725191
- Sponsor's protocol ID
- NCI-2012-02163
- Other IDs
- NCI-2012-02163, COG-ADVL1111, ADVL1111, ADVL1111, U01CA097452
- Status last verified
- May 2015
- First submitted
- 8 Nov 2012
- Last updated
- 2 Jul 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of the c-Met Inhibitor, Tivantinib (ARQ 197) in Children With Relapsed or Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT01725191
- Acronym / sponsor ID
- NCI-2012-02163
- Conditions
- Childhood Solid Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2012
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 12 Nov 2012 (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.
This phase I trial studies the side effects and best dose of tivantinib in treating younger patients with solid tumors that have returned after a period of improvement or have not responded to treatment. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of tivantinib administered orally twice daily to children with refractory solid tumors.
II. To define and describe the toxicities of tivantinib administered on this schedule.
III. To characterize the pharmacokinetics of tivantinib (capsule as well as powder formulation) in children with refractory cancer.
SECONDARY OBJECTIVES:
- To preliminarily define the antitumor activity of tivantinib within the confines of a phase 1 study.
II. To preliminarily investigate whether cytochrome P450 (CYP450) polymorphisms impact pharmacokinetics or toxicity of tivantinib.
III. To preliminarily investigate whether tumor c-Met and/or hepatocyte growth factor (HGF) expression or downstream c-Met signaling correlate with clinical response to tivantinib.
OUTLINE: This is a dose-escalation study.
Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
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, Other: Pharmacological Study, Drug: TivantinibPatients receive tivantinib PO BID on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 13 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (30 listed)
- PART A: Patients on dose levels -1 or 1 must have a body surface area (BSA) >= 0.65 m^2 at the time of study enrollment; patients on dose levels 2 or 3 must have a BSA >= 0.45 m^2 at the time of study enrollment
- PART B: There is no minimum body surface area requirement for patients in part B
- Patients with relapsed or refractory solid tumors including central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
- Patients must have either measurable or evaluable disease
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
Key exclusion criteria (12 listed)
- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are currently receiving other anti-cancer agents are not eligible
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
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) |
| Pharmacological StudyCorrelative studies | Other | Treatment (tivantinib) |
| TivantinibAlso: ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197Given PO | Drug | Treatment (tivantinib) |
Primary outcome
MTD defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: 28 days
Pharmacokinetic (PK) parameters of tivantinib
Time frame: Pre-dose, 1, 2, 4, 6 and 8-12 hours day 1 of course 1; pre-dose day 1 of course 2
The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
1 secondary outcome
Disease response assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Time frame: Up to 30 days after completion of study treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2015.
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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.
James Geller principal investigator
COG Phase I Consortium
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Tivantinib in people with Childhood Solid Neoplasm, run by National Cancer Institute (NCI) at 20 sites in 2 countries.
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 30 inclusion and 12 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 2 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
MTD defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: 28 days). 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 2 Jul 2015.