Advanced Solid TumorsPhase 1NCT00874042

Dose Escalation Study of ARQ 197 in Combination With Gemcitabine in Adult Patients With Advanced Solid Tumors

A Phase 1 study testing Treatment with ARQ 197 in combination with gemcitabine in people with Advanced Solid Tumors, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 4 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 is an open-label, dose-escalation/de-escalation study of ARQ 197 administered orally in combination with gemcitabine. The study is designed to determine the safety, tolerability and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of ARQ 197 when administered in combination with gemcitabine to… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumors
What is being tested?: Treatment with ARQ 197 in combination with gemcitabine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 74 participants
Where: 4 sitesUnited States
Study dates: Mar 2009to Apr 2011
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

Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
18 year of age or older
Histologically or cytologically confirmed locally advanced, inoperable or metastatic primary solid tumors
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN with metastatic liver disease

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Hemoglobin ≥ 10 g/dl (or ≥ 9 g/dl for expanded cohort)
Total bilirubin ≤ 1.5 x ULN
Serum creatinine ≤ 1.5 x ULN
Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
Platelets ≥ 100 x 10^9/L
Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug
Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received

Who cannot join

Other cancer within the last three years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin
Previous anti-cancer chemotherapy, radiotherapy, major surgery, immunotherapy or investigational agents within 4 weeks prior to the first day of study defined treatment
History of cardiac disease: congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (version 3.0), or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred > 6 months prior to study entry is permitted)
Active clinically serious infections defined as ≥ Grade 2 according to NCI CTCAE, version 3.0
Substance abuse, medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results
Any condition that is unstable or which could jeopardize the safety of the patient and his/her protocol compliance

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Known human immunodeficiency virus (HIV) infection
Pregnancy or breast-feeding
Inability to swallow oral medications
Significant gastrointestinal disorder, in the opinion of the Investigator, could interfere with the absorption of ARQ 197 and/or gemcitabine (e.g. significant, uncontrolled inflammatory bowel disease or extensive small bowel resection)
Central nervous system metastases

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Study site
Atlanta, Georgia, 30341
Study site
Houston, Texas, 77024
Study site
Nashville, Tennessee, 37203
Study site
Oklahoma City, Oklahoma, 73104

Other trials in United States

About this study

Official title: A Phase 1 Dose Escalation Study of ARQ 197 Administered in Combination With Gemcitabine in Adult Patients With Advanced Solid Tumors

Read the detailed description

Enrollment of an initial cohort of 3 or 6 patients will follow the traditional "3 + 3" dose escalation scheme. These patients will be treated with ARQ 197 and gemcitabine. ARQ 197 will be administered by mouth BID continuously. Gemcitabine will be administered by intravenous infusion over 30 minutes once weekly for 3 consecutive weeks followed by a week of rest. The dosing schedules of ARQ 197 and gemcitabine will be as described below.

ARQ 197 will be administered per the following cohorts, starting from week 1 of treatment.

Cohort------ARQ 197 (mg BID)

0-----------120, continuously

1-----------240, continuously

A-----------120 (repeated treatments of 2 weeks followed by a 1 week pause)

B-----------240 (repeated treatments of 2 weeks followed by a 1 week pause)

C-----------360 (repeated treatments of 2 weeks followed by a 1 week pause)

D-----------360 (repeated treatments of 3 weeks followed by a 1 week pause)

E-----------360, continuously

In case of DLT, intermediate dosing cohorts will be explored, administering ARQ 197 for 5 days instead of 7 during the weeks of ARQ 197 administration.

For cohorts 0 and 1, gemcitabine is administered at the dose of 1000mg/sqm from week 1 of treatment, 4 weeks in a row for the first month, then for 3 consecutive weeks followed by a week of pause. For all other cohorts, gemcitabine will be administered starting from week 2 of treatment at the dose of 1000mg/sqm, for 3 consecutive weeks followed by a week of pause.

Additional treatment cohorts may be enrolled to explore intermediate, higher or lower doses of ARQ 197, as indicated by the tolerability, safety profile, and pharmacokinetic (PK) profile.

Once a safe and recommended dose level is determined, an Expanded Cohort of up to 60 patients with non-resectable cholangiocarcinoma (10 patients), breast carcinoma (10 patients), ovarian carcinoma (10 patients), endometrial carcinoma and carcinoma of the cervix (10 patients in total, at least five with endometrial carcinoma). Each group of 10 patients may enroll up to three patients who received at least 5-week gemcitabine treatment. The cohort will also include up to 20 patients with pancreatic carcinoma (up to five out of 20 patients may have received at least 5-week gemcitabine treatment).

Conditions: Advanced Solid Tumors
Being tested: Treatment with ARQ 197 in combination with gemcitabine
Keywords: dose escalation, safety, tolerability, tumor, PK
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Treatment with ARQ 197 in combination with gemcitabineDrug
Enrollment of an initial cohort of 3 or 6 patients will follow the traditional "3 + 3" dose escalation scheme. These patients will be treated with ARQ 197 and gemcitabine. ARQ 197 will be administered by mouth BID continuously. Gemcitabine will be administered by intravenous infusion over 30 minutes once weekly for 3 consecutive weeks followed by a week of rest.

Study groups in NCT00874042
Study group	Role	What they receive
ARQ 197 in combination with gemcitabine	Experimental	Not described Receives: Drug: Treatment with ARQ 197 in combination with gemcitabine

What is being measured

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

To determine the safety, tolerability and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of ARQ 197 when administered in combination with gemcitabine.
Measured: Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.

Secondary outcomes (3)

To determine the pharmacokinetic profiles of ARQ 197, gemcitabine and dFdU inactive metabolite of gemcitabine when administered in combination.
To assess the preliminary anti-tumor activity of ARQ 197 when administered in combination with gemcitabine.
Measured: Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.
To evaluate dynamic changes of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and soluble c-Met in patients' peripheral blood that are associated with treatment of ARQ 197 plus gemcitabine.
Measured: Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2009Apr 2011

First posted2 Apr 2009 (estimated)
Study startMar 2009
Primary completionFeb 2011
Study completionApr 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
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: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 74 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00874042
Sponsor's protocol ID: ARQ 197-117
Status last verified: Jul 2012
First submitted: 1 Apr 2009
Last updated: 23 Jul 2012
Results posted: No
Data monitoring committee: No

Publications

Pant S, Saleh M, Bendell J, Infante JR, Jones S, Kurkjian CD, Moore KM, Kazakin J, Abbadessa G, Wang Y, Chen Y, Schwartz B, Camacho LH. A phase I dose escalation study of oral c-MET inhibitor tivantinib (ARQ 197) in combination with gemcitabine in patients with solid tumors. Ann Oncol. 2014 Jul;25(7):1416-1421. doi: 10.1093/annonc/mdu157. Epub 2014 Apr 15.
PubMed 24737778

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Dose Escalation Study of ARQ 197 Administered in Combination With Gemcitabine in Adult Patients With Advanced Solid Tumors
ClinicalTrials.gov ID: NCT00874042
Acronym / sponsor ID: ARQ 197-117
Conditions: Advanced Solid Tumors
Keywords: dose escalation, safety, tolerability, tumor, PK
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 74 participants (actual)
Lead sponsor: ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)Industry (pharma, biotech, devices)
Study start: Mar 2009
Primary completion: Feb 2011 (actual)
Study completion: Apr 2011 (actual)
First posted: 2 Apr 2009 (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.

Detailed description

ARQ 197 will be administered per the following cohorts, starting from week 1 of treatment.

Cohort------ARQ 197 (mg BID)

0-----------120, continuously

1-----------240, continuously

A-----------120 (repeated treatments of 2 weeks followed by a 1 week pause)

B-----------240 (repeated treatments of 2 weeks followed by a 1 week pause)

C-----------360 (repeated treatments of 2 weeks followed by a 1 week pause)

D-----------360 (repeated treatments of 3 weeks followed by a 1 week pause)

E-----------360, continuously

In case of DLT, intermediate dosing cohorts will be explored, administering ARQ 197 for 5 days instead of 7 during the weeks of ARQ 197 administration.

Additional treatment cohorts may be enrolled to explore intermediate, higher or lower doses of ARQ 197, as indicated by the tolerability, safety profile, and pharmacokinetic (PK) profile.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
ARQ 197 in combination with gemcitabine	Experimental	Drug: Treatment with ARQ 197 in combination with gemcitabine

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
18 year of age or older
Histologically or cytologically confirmed locally advanced, inoperable or metastatic primary solid tumors
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1

Key exclusion criteria (11 listed)

Other cancer within the last three years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin
Previous anti-cancer chemotherapy, radiotherapy, major surgery, immunotherapy or investigational agents within 4 weeks prior to the first day of study defined treatment
History of cardiac disease: congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (version 3.0), or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred > 6 months prior to study entry is permitted)
Active clinically serious infections defined as ≥ Grade 2 according to NCI CTCAE, version 3.0
Substance abuse, medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results

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
Treatment with ARQ 197 in combination with gemcitabineEnrollment of an initial cohort of 3 or 6 patients will follow the traditional "3 + 3" dose escalation scheme. These patients will be treated with ARQ 197 and gemcitabine. ARQ 197 will be administered by mouth BID continuously. Gemcitabine will be administered by intravenous infusion over 30 minutes once weekly for 3 consecutive weeks followed by a week of rest.	Drug	ARQ 197 in combination with gemcitabine

Primary outcome

To determine the safety, tolerability and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of ARQ 197 when administered in combination with gemcitabine.
Time frame: Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.

3 secondary outcomes

To determine the pharmacokinetic profiles of ARQ 197, gemcitabine and dFdU inactive metabolite of gemcitabine when administered in combination.
To assess the preliminary anti-tumor activity of ARQ 197 when administered in combination with gemcitabine.
Time frame: Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.
To evaluate dynamic changes of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and soluble c-Met in patients' peripheral blood that are associated with treatment of ARQ 197 plus gemcitabine.
Time frame: Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.

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 23 Jul 2012.
Derived from this study: PubMed 24737778Pant S, Saleh M, Bendell J, Infante JR, Jones S, Kurkjian CD, Moore KM, Kazakin J, Abbadessa G, Wang Y, Chen Y, Schwartz B, Camacho LH. A phase I dose escalation study of oral c-MET inhibitor tivantinib (ARQ 197) in combination with gemcitabine in patients with solid tumors. Ann Oncol. 2014 Jul;25(7):1416-1421. doi: 10.1093/annonc/mdu157. Epub 2014 Apr 15.

Related trials for Advanced Solid Tumors

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
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RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
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Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
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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.

The record lists no contact. Use the official record to reach the sponsor.

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 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 23 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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?

To determine the safety, tolerability and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of ARQ 197 when administered in combination with gemcitabine. (time frame: Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.). 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 NCT00874042, which also lists 1 linked publication.

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 23 Jul 2012.