Adult Solid NeoplasmPhase 1NCT01654965
Tivantinib and Topotecan Hydrochloride in Treating Patients With Advanced or Metastatic Solid Tumors
A Phase 1 study testing Laboratory Biomarker Analysis, Pegfilgrastim and Pharmacological Study in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 7 sites in United States.
Trial summary
This phase I trial studies the side effects and best dose of tivantinib and topotecan hydrochloride in treating patients with advanced or metastatic solid tumors. Tivantinib and topotecan hydrochloride 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
- Adult Solid Neoplasm
- What is being tested?
- Laboratory Biomarker Analysis, Pegfilgrastim and Pharmacological Study
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 7 sitesUnited States
- Study dates
- 24 Jul 2012to 29 Mar 2018
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; for the expansion group, patients must have histologically or cytologically confirmed small cell lung cancer previously treated with one or more chemotherapy or chemoradiotherapy regimens, at least one of which must have been platinum-based
- As of amendment dated 01/24/2014 the study will not be pursuing an expansion cohort in small cell lung cancer
- Karnofsky >= 60%
- Life expectancy of greater than 12 weeks
- Hemoglobin >= 9.0 g/dL
- Leukocytes >= 3,000/mcL
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- 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 (=< 5 X institutional upper limit of normal if the rise can be attributed to liver metastases)
- 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
- 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 due to agents administered more than 4 weeks earlier
- Patients who are receiving any other investigational agents
- Patients with untreated brain metastases should be excluded from this clinical trial; however patients with stable brain disease (off corticosteroids) at least 2 weeks after completion of appropriate therapy for their brain metastases are eligible; patients who require enzyme-inducing anti-convulsants (EIAC) should be switched to non-EIAC and be on a stable dose of the new agent for at least 2 weeks prior to treatment on this protocol
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197 or topotecan
- The metabolism and consequently overall pharmacokinetics of ARQ 197 could be altered by inhibitors and/or inducers or other substrates of cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (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; caution should be applied when CYP2C19 inhibitors such as omeprazole, fluvoxamine, fluconazole, ticlopidine, rabeprazole, fluoxetine, and moclobemide, or strong CYP3A4 inhibitors such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, ciprofloxacin, telithromycin, troleandomycin (TAO), or voriconazole, are used as concomitant therapy; because the lists of these agents are changing, it is important to consult an 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; breastfeeding should be discontinued if the mother is treated with ARQ 197
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patients previously treated with topotecan are ineligible
- Patients previously treated with ARQ 197 are ineligible
- Patients unable to swallow ARQ 197 pills are ineligible
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
City of Hope South Pasadena
South Pasadena, California, 91030
About this study
Official title: A Phase I Study of ARQ 197 in Combination With IV Topotecan in Advanced Solid Tumors With an Expansion Cohort in Small Cell Lung Cancer
This phase I trial studies the side effects and best dose of tivantinib and topotecan hydrochloride in treating patients with advanced or metastatic solid tumors. Tivantinib and topotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To establish the recommended phase 2 dose (RP2D) for the combination of ARQ 197 (tivantinib) and intravenous (IV) topotecan (topotecan hydrochloride).
II. To describe the toxicities of ARQ 197 and IV topotecan at each dose studied.
III. To characterize the pharmacokinetic behavior of ARQ 197 given concurrent use of IV topotecan.
IV. To document all clinical responses to ARQ 197 with IV topotecan.
OUTLINE: This is a dose-escalation study of tivantinib and topotecan hydrochloride.
Patients receive tivantinib orally (PO) twice daily (BID) on days 1-21, topotecan hydrochloride IV over 30 minutes on days 1-5, and pegfilgrastim subcutaneously (SC) on day 6. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
- Conditions
- Adult Solid Neoplasm
- Being tested
- Laboratory Biomarker Analysis, Pegfilgrastim, Pharmacological Study, Tivantinib, Topotecan Hydrochloride
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
PegfilgrastimBiological
Also called Filgrastim SD-01, filgrastim-SD/01, HSP-130, Neulasta
Given SC
Correlative studies
TivantinibDrug
Also called ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197
Given PO
Topotecan HydrochlorideDrug
Also called Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tivantinib, topotecan hydrochloride, pegfilgrastim) | Experimental | Patients receive tivantinib PO BID on days 1-21, topotecan hydrochloride IV over 30 minutes on days 1-5, and pegfilgrastim SC on day 6. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Biological: Pegfilgrastim; Other: Pharmacological Study; Drug: Tivantinib; Drug: Topotecan Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events graded according to the NCI CTCAE version 4.0
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTCAE), attribution, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
Measured: Up to 4 weeks
Secondary outcomes (3)
Tumor response as evaluated by Response Evaluation Criteria in Solid Tumors version 1.1
All responses will be reported; because of the potential heterogeneity of the patients, no attempt will be made to summarize these for the patients included in the dose escalation phase.
Measured: Up to 4 weeks
Progression-free survival (PFS)
PFS will be reported; because of the potential heterogeneity of the patients, no attempt will be made to summarize these for the patients included in the dose escalation phase.
Measured: The time from start of treatment until first evidence of disease progression or death due to any cause, assessed up to 4 weeks
Overall survival (OS)
OS will be reported; because of the potential heterogeneity of the patients, no attempt will be made to summarize these for the patients included in the dose escalation phase.
Measured: The time from start of treatment until death due to any cause, assessed up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2012 (estimated)
- Study start24 Jul 2012
- Primary completion29 Mar 2018
- Study completion29 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult 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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Barbara Gitlitz, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01654965
- Sponsor's protocol ID
- NCI-2012-01220
- Other IDs
- NCI-2012-01220, CDR0000738072, PHI-68, PHI-68, 9152, P30CA033572, U01CA062505, UM1CA186717
- Status last verified
- Mar 2018
- First submitted
- 30 Jul 2012
- Last updated
- 3 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of ARQ 197 in Combination With IV Topotecan in Advanced Solid Tumors With an Expansion Cohort in Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01654965
- Acronym / sponsor ID
- NCI-2012-01220
- Conditions
- Adult Solid Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 24 Jul 2012 (actual)
- Primary completion
- 29 Mar 2018 (actual)
- Study completion
- 29 Mar 2018 (actual)
- First posted
- 1 Aug 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 and topotecan hydrochloride in treating patients with advanced or metastatic solid tumors. Tivantinib and topotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To establish the recommended phase 2 dose (RP2D) for the combination of ARQ 197 (tivantinib) and intravenous (IV) topotecan (topotecan hydrochloride).
II. To describe the toxicities of ARQ 197 and IV topotecan at each dose studied.
III. To characterize the pharmacokinetic behavior of ARQ 197 given concurrent use of IV topotecan.
IV. To document all clinical responses to ARQ 197 with IV topotecan.
OUTLINE: This is a dose-escalation study of tivantinib and topotecan hydrochloride.
Patients receive tivantinib orally (PO) twice daily (BID) on days 1-21, topotecan hydrochloride IV over 30 minutes on days 1-5, and pegfilgrastim subcutaneously (SC) on day 6. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
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, topotecan hydrochloride, pegfilgrastim) | Experimental | Other: Laboratory Biomarker Analysis, Biological: Pegfilgrastim, Other: Pharmacological Study, Drug: Tivantinib, Drug: Topotecan HydrochloridePatients receive tivantinib PO BID on days 1-21, topotecan hydrochloride IV over 30 minutes on days 1-5, and pegfilgrastim SC on day 6. Courses repeat every 21 days 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 (13 listed)
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; for the expansion group, patients must have histologically or cytologically confirmed small cell lung cancer previously treated with one or more chemotherapy or chemoradiotherapy regimens, at least one of which must have been platinum-based
- Karnofsky >= 60%
- Life expectancy of greater than 12 weeks
- Hemoglobin >= 9.0 g/dL
- Leukocytes >= 3,000/mcL
Key exclusion criteria (12 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 due to agents administered more than 4 weeks earlier
- Patients who are receiving any other investigational agents
- Patients with untreated brain metastases should be excluded from this clinical trial; however patients with stable brain disease (off corticosteroids) at least 2 weeks after completion of appropriate therapy for their brain metastases are eligible; patients who require enzyme-inducing anti-convulsants (EIAC) should be switched to non-EIAC and be on a stable dose of the new agent for at least 2 weeks prior to treatment on this protocol
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197 or topotecan
- The metabolism and consequently overall pharmacokinetics of ARQ 197 could be altered by inhibitors and/or inducers or other substrates of cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (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; caution should be applied when CYP2C19 inhibitors such as omeprazole, fluvoxamine, fluconazole, ticlopidine, rabeprazole, fluoxetine, and moclobemide, or strong CYP3A4 inhibitors such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, ciprofloxacin, telithromycin, troleandomycin (TAO), or voriconazole, are used as concomitant therapy; because the lists of these agents are changing, it is important to consult an 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, topotecan hydrochloride, pegfilgrastim) |
| PegfilgrastimAlso: Filgrastim SD-01, filgrastim-SD/01, HSP-130, NeulastaGiven SC | Biological | Treatment (tivantinib, topotecan hydrochloride, pegfilgrastim) |
| Pharmacological StudyCorrelative studies | Other | Treatment (tivantinib, topotecan hydrochloride, pegfilgrastim) |
| TivantinibAlso: ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197Given PO | Drug | Treatment (tivantinib, topotecan hydrochloride, pegfilgrastim) |
| Topotecan HydrochlorideAlso: Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HClGiven IV | Drug | Treatment (tivantinib, topotecan hydrochloride, pegfilgrastim) |
Primary outcome
Incidence of adverse events graded according to the NCI CTCAE version 4.0
Time frame: Up to 4 weeks
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTCAE), attribution, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
3 secondary outcomes
Tumor response as evaluated by Response Evaluation Criteria in Solid Tumors version 1.1
Time frame: Up to 4 weeks
Progression-free survival (PFS)
Time frame: The time from start of treatment until first evidence of disease progression or death due to any cause, assessed up to 4 weeks
Overall survival (OS)
Time frame: The time from start of treatment until death due to any cause, assessed up to 4 weeks
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 3 Apr 2018.
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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.
Barbara Gitlitz principal investigator
City of Hope Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Laboratory Biomarker Analysis, Pegfilgrastim and Pharmacological Study in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 7 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 13 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 3 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 7 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 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?
Incidence of adverse events graded according to the NCI CTCAE version 4.0 (time frame: Up to 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2018.