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Adult Solid NeoplasmPhase 1NCT01625156

Tivantinib and Temsirolimus in Treating Patients With Solid Tumors That is Metastatic or Cannot be Removed by Surgery

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Temsirolimus in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of tivantinib when given in combination with temsirolimus in treating patients with solid tumors that have spread to other parts of the body or cannot be removed by surgery. 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, Pharmacological Study and Temsirolimus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
2 sitesUnited States
Study dates
May 2012to Oct 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which standard curative or palliative systemic therapies (such as chemotherapy, targeted therapies or immunotherapy) do not exist or are no longer effective
  • Patients must have measurable or evaluable disease, as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • No prior treatment with temsirolimus or an agent specifically targeting met proto-oncogene (c-Met)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Hemoglobin >= 9.0 g/dL
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  • Leukocytes >= 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]) =< institutional upper limit of normal
  • Serum creatinine =< institutional upper limit of normal or creatinine clearance (either estimated or calculated) >= 60 mL/min/1.73 m for patients with creatinine levels above institutional normal
  • Fasting glucose =< 150 mg/dL
  • Fasting cholesterol level < 350 mg/dl
  • Fasting triglycerides =< 300 mg/dl
  • Phosphorus >= institutional lower limit of normal (repletion allowed)
  • Patients with treated, stable brain metastases are allowed to enroll; patients must be at least 4 weeks from radiation and off any medications used to treat brain metastases including steroids; patients are allowed to be on antiepileptic medications that are not metabolized by cytochrome P450 3A4 or 2C19; patients with brain metastases must have stable brain imaging within 4 weeks prior to starting study
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and up to 3 months after discontinuation of study drugs; 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; 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
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Any of the following:
  • Chemotherapy =< 3 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C)
  • Radiotherapy, endocrine therapy or targeted therapy for malignancy =< 2 weeks prior to registration
  • Patients who have not recovered (=< grade 1) from adverse events due to agents administered more than 4 weeks earlier (tolerable grade 2 adverse events may be allowed at the discretion of the investigator; diarrhea must be grade 1 or lower without the scheduled use of antidiarrheal medications)
  • Prior anticancer therapy with an mammalian target of rapamycin (mTOR) inhibitor (everolimus, temsirolimus, desferolimus) or agent specifically targeting c-Met
  • Patients who are receiving any other investigational agents
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  • Patients may not have clinically symptomatic hypothyroidism; testing is not required for eligibility
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197 or temsirolimus
  • ARQ 197 is a sensitive substrate for 2C19 and 3A4, a strong inhibitor for 2C19 and moderate inhibitor by in vitro data only for 3A4; temsirolimus is a sensitive substrate for CYP 3A4 and a weak inhibitor of CYP2D6 and CYP3A4/5; per the UWinRx Drug Interaction Policy, the following medications are contraindicated or must be used with caution
  • Contraindicated:
  • CYP2C19 sensitive substrates (unless close monitoring with labs or drug levels with dose adjustments is feasible), inducers, and moderate/strong inhibitors of CYP2C19; patients taking these concurrent medications are ineligible unless they can be switched to alternative medications prior to initiation of the study
  • CYP3A4/5 inducers and moderate/strong inhibitors of CYP3A4/5; patients taking these concurrent medications are ineligible unless they can be switched to alternative medications prior to initiation of the study
  • Use with caution:
  • CYP2C19 non-sensitive substrates with a narrow therapeutic window and weak inhibitors are permitted if no acceptable alternatives are available as determined by the treating physician; however, caution should be used; consider monitoring with labs or drug levels and dose adjustments of the medication if feasible; other non-sensitive substrates are allowed on study
  • CYP3A4/5 sensitive substrates and any non-sensitive substrates with a narrow therapeutic window and weak inhibitors are permitted if no acceptable alternatives are available as determined by the treating physician; however, caution should be used; consider monitoring with labs or drug levels and dose adjustments of the medication if feasible; other non-sensitive substrates are allowed on study
  • CYP2D6 inducers, moderate/strong inhibitors or sensitive substrates are permitted if no acceptable alternatives are available; however, caution should be used; other non-sensitive substrates or weak inhibitors of CYP2D6 are allowed on study
  • 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 (< 50 beats per minute [bpm]) 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 (as determined by the investigator); myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring > 6 months prior to study entry is permitted)
  • Patients with uncontrolled diabetes (as determined by the investigator); well-controlled diabetic patients with fasting glucose < 150 are eligible if they have been on stable doses of medications for diabetes for at least 4 weeks prior to study entry
  • 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; breastfeeding should be discontinued if the mother is treated on this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption of pills; patients must be able to swallow pills

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Wisconsin Clinical Cancer Center

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: A Phase 1 Study of ARQ 197 in Combination With Temsirolimus in Advanced Solid Tumors

This phase I trial studies the side effects and best dose of tivantinib when given in combination with temsirolimus in treating patients with solid tumors that have spread to other parts of the body or cannot be removed by surgery. Tivantinib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ARQ197 (tivantinib) in combination with temsirolimus in adult subjects with advanced solid tumors who are extensive cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) metabolizers.

SECONDARY OBJECTIVES:

  1. To characterize the tolerability and/or MTD of ARQ 197 and in combination with temsirolimus in adult subjects who are poor CYP2C19 metabolizers (CYP2C19*2/*2, *2/*3 or *3/*3 polymorphisms).

II. To identify the pharmacokinetic parameters of ARQ 197 after a single dose and at steady state in extensive and poor CYP2C19 metabolizers.

III. To assess the steady state pharmacokinetics of ARQ 197 alone and in combination with temsirolimus.

IV. To determine impact of cytochrome P450, family 3, subfamily A, polypeptide 4/cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A4/5) polymorphisms on ARQ 197 pharmacokinetic parameters.

  1. To determine the pharmacokinetics of temsirolimus and its active metabolite sirolimus in combination with ARQ 197 and compare to historical pharmacokinetic data.

VI. To determine impact of CYP3A4/5 polymorphisms on temsirolimus pharmacokinetic parameters.

VII. To describe the dose-limiting toxicities and determine the safety profile of the combination of ARQ 197 and temsirolimus.

VIII. To evaluate the preliminary anti-tumor activity of ARQ197 and temsirolimus in patients with advanced solid tumors.

IX. To correlate archived tumor tissue expression of c-Met with objective response to ARQ 197 and temsirolimus therapy.

OUTLINE: This is a dose-escalation study of tivantinib.

Patients receive tivantinib orally (PO) twice daily (BID) and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22 (days 8, 15, 22, and 29 of course 1). Courses repeat every 28 days (35 days in course 1) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 4 weeks.

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, Temsirolimus, 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

  • Pharmacological StudyOther

    Correlative studies

  • TemsirolimusDrug

    Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog

    Given IV

  • TivantinibDrug

    Also called ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197

    Given PO

Study groups in NCT01625156
Study groupRoleWhat they receive
Treatment (tivantinib, temsirolimus)ExperimentalPatients receive tivantinib PO BID and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 (days 8, 15, 22, and 29 of course 1). Courses repeat every 28 days (35 days in course 1) in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus; Drug: Tivantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD and RP2D of tivantinib in combination with temsirolimus defined as the highest safely tolerated dose where 0/6 or 1/6 patients experience a dose-limiting toxicity (DLT) and two or more patients have experienced a DLT at the next higher dose level

    Categorized according to NCI Common Toxicity Criteria version 4.0.

    Measured: First 35 days

Secondary outcomes (3)

  1. Incidence of adverse events and toxicities of tivantinib in combination with temsirolimus

    Categorized according to NCI Common Toxicity Criteria version 4.0. Summarized in terms of type, severity (grade 1-5), and dose level in tabular format. Wilson score method will be used to construct confidence intervals.

    Measured: Up to 4 weeks after completion of study treatment

  2. Pharmacokinetic analysis

    Plots of individual, mean, and median plasma concentration versus time will be presented where appropriate. The comparison of PK parameters between dose levels will be performed using a two-sample t-test.

    Measured: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours (days 1 and 7), pre-dose and 0.5 hours (day 8), pre-dose (days 15 and 22 of course 1 and day 1 of course 2)

  3. Response rate validated by the RECIST criteria

    Summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. Ninety-five percent confidence intervals will be constructed using the Wilson Score method.

    Measured: Up to 4 weeks 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.

  1. First posted21 Jun 2012 (estimated)
  2. Study startMay 2012
  3. Primary completionSep 2015
  4. Study completionOct 2015

Resources

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
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01625156
Sponsor's protocol ID
NCI-2012-00949
Other IDs
NCI-2012-00949, NCI 9145, 905854-02-06, NCI-2012-00974, CO 11914, 9145, P30CA014520, U01CA062491
Status last verified
May 2015
First submitted
18 Jun 2012
Last updated
20 Oct 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Temsirolimus in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 2 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 19 inclusion and 22 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 20 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

MTD and RP2D of tivantinib in combination with temsirolimus defined as the highest safely tolerated dose where 0/6 or 1/6 patients experience a dose-limiting toxicity (DLT) and two or more patients have experienced a DLT at the next higher dose level (time frame: First 35 days). 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 NCT01625156.

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 20 Oct 2015.

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