Cancer, Advanced Solid TumorsPhase 1ARQ 197NCT00612209
A Phase 1 Study of ARQ 197 in Adult Patients With Advanced Solid Tumors
A Phase 1 study testing ARQ 197 in people with Cancer, Advanced Solid Tumors, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 1 site in United Kingdom.
Trial summary
This is an open label, single arm, dose escalation study of ARQ 197 in patients with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Advanced Solid Tumors
- What is being tested?
- ARQ 197
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2007to Feb 2010
- 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
- Signed written informed consent must be obtained and documented according to ICH GCP, the local regulatory requirements, and permission to use private health information in accordance with HIPPA prior to study-specific screening procedures
- A histologically or cytologically confirmed advanced solid tumor, including 10 patients with advanced prostate cancers in the expansion cohort.
- ≥ 18 years of age.
- Patients must have accessible tumor that is safely amenable to tumor biopsies.
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
- Tumor imageable by DCE-MRI preferably > 3cm in abdomen, pelvis, head/neck or peripheral limb (only for 12 patients undergoing MRI studies including DCE-MRI and DW-MRI in the expanded cohort)
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- Karnofsky performance status (KPS) ≥ 70% or Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last ARQ 197 dose
- Females of childbearing potential must have a negative serum pregnancy test
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5.0 × ULN with metastatic liver disease
- Hemoglobin ≥ 10 g/dl
- Total bilirubin ≤ 1.5 × ULN
- Creatinine ≤ 1.5 x ULN
- Absolute neutrophil count ≥ 1.5 x 10^9/L
- Platelets ≥ 100 x 10^9/L
- The following inclusion criteria apply to patients with prostate cancer only:
- Histologically documented adenocarcinoma of the prostate, clinically refractory or resistant to hormone therapy, as documented by progression following castration
- PSA or radiological evidence for progressive prostate cancer
- Ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective LHRH analogue therapy before and during the trial.
- Castrate testosterone level [< 50 ng/dL or < 2.00 nmol/L (nmol/L x 28.8 = ng/dL)]
Who cannot join
- Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks prior to first dose of ARQ 197
- Surgery within 4 weeks prior to first dose
- Known untreated brain metastases
- Pregnant or breastfeeding
- Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
- Unable or unwilling to swallow ARQ 197 capsules twice daily
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- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements
- For patients undergoing magnetic resonance imaging (MRI) studies (including DCE-MRI and DW-MRI) in the expanded cohort:
- Contraindications to MRI, e.g. contraindicated metal implants
- Patients with Creatinine > x1 ULN
- Patients without antecubital fossa venous access
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Dose Escalation Study of ARQ 197 Given Twice Daily Continuously in Adult Patients With Advanced Solid Tumors
This is an open label, single arm, dose escalation study of ARQ 197 in patients with advanced solid tumors.
Read the detailed description
Patients will take ARQ 197 orally twice daily continuously at dose levels specified for their respective dose cohorts. The ARQ 197 starting dose will be a total daily dose of 200 mg (100 mg bid). ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment is permitted. A treatment cycle is designed as four weeks (28 days) and will be repeated without therapy interruption.
- Conditions
- Cancer, Advanced Solid Tumors
- Being tested
- ARQ 197
- Keywords
- ARQ 197, advanced solid tumors, phase 1, dose escalation, pharmacodynamics, safety
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARQ 197Drug
Treatment with ARQ 197
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: ARQ 197 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, tolerability
Measured: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
Secondary outcomes (3)
To evaluate pharmacodynamics of phosphorylated c-Met, total c-Met, apoptosis marker (TUNEL) and phosphorylated FAK in tumor tissue correlated with administration of ARQ 197.
Measured: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
To assess the preliminary anti-tumor activity of ARQ 197.
Measured: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
To determine the pharmacokinetic (PK) profile of ARQ 197 with continuously twice daily oral dosing schedule.
Measured: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, 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.
- First posted11 Feb 2008 (estimated)
- Study startApr 2007
- Primary completionJan 2010
- Study completionFeb 2010
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 Cancer, 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
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Johann DeBono, MBChB, FRCP, Principal investigator, The Royal Marsden Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00612209
- Sponsor's protocol ID
- ARQ 197-103
- Acronym
- ARQ 197
- Status last verified
- Jul 2012
- First submitted
- 29 Jan 2008
- Last updated
- 23 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Yap TA, Olmos D, Brunetto AT, Tunariu N, Barriuso J, Riisnaes R, Pope L, Clark J, Futreal A, Germuska M, Collins D, deSouza NM, Leach MO, Savage RE, Waghorne C, Chai F, Garmey E, Schwartz B, Kaye SB, de Bono JS. Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies. J Clin Oncol. 2011 Apr 1;29(10):1271-9. doi: 10.1200/JCO.2010.31.0367. Epub 2011 Mar 7.
PubMed 21383285
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 Given Twice Daily Continuously in Adult Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00612209
- Acronym / sponsor ID
- ARQ 197 / ARQ 197-103
- Conditions
- Cancer, Advanced Solid Tumors
- Keywords
- ARQ 197, advanced solid tumors, phase 1, dose escalation, pharmacodynamics, safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 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
- Apr 2007
- Primary completion
- Jan 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 11 Feb 2008 (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 is an open label, single arm, dose escalation study of ARQ 197 in patients with advanced solid tumors.
Detailed description
Patients will take ARQ 197 orally twice daily continuously at dose levels specified for their respective dose cohorts. The ARQ 197 starting dose will be a total daily dose of 200 mg (100 mg bid). ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment is permitted. A treatment cycle is designed as four weeks (28 days) and will be repeated without therapy interruption.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: ARQ 197 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Signed written informed consent must be obtained and documented according to ICH GCP, the local regulatory requirements, and permission to use private health information in accordance with HIPPA prior to study-specific screening procedures
- A histologically or cytologically confirmed advanced solid tumor, including 10 patients with advanced prostate cancers in the expansion cohort.
- ≥ 18 years of age.
- Patients must have accessible tumor that is safely amenable to tumor biopsies.
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
Key exclusion criteria (11 listed)
- Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks prior to first dose of ARQ 197
- Surgery within 4 weeks prior to first dose
- Known untreated brain metastases
- Pregnant or breastfeeding
- Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
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 |
|---|---|---|
| ARQ 197Treatment with ARQ 197 | Drug | 1 |
Primary outcome
Safety, tolerability
Time frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
3 secondary outcomes
To evaluate pharmacodynamics of phosphorylated c-Met, total c-Met, apoptosis marker (TUNEL) and phosphorylated FAK in tumor tissue correlated with administration of ARQ 197.
Time frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
To assess the preliminary anti-tumor activity of ARQ 197.
Time frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met
To determine the pharmacokinetic (PK) profile of ARQ 197 with continuously twice daily oral dosing schedule.
Time frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, 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 21383285Yap TA, Olmos D, Brunetto AT, Tunariu N, Barriuso J, Riisnaes R, Pope L, Clark J, Futreal A, Germuska M, Collins D, deSouza NM, Leach MO, Savage RE, Waghorne C, Chai F, Garmey E, Schwartz B, Kaye SB, de Bono JS. Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies. J Clin Oncol. 2011 Apr 1;29(10):1271-9. doi: 10.1200/JCO.2010.31.0367. Epub 2011 Mar 7.
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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.
Johann DeBono, MBChB, FRCP principal investigator
The Royal Marsden Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ARQ 197 in people with Cancer, Advanced Solid Tumors, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 1 site in United Kingdom.
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 20 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 1 site in United Kingdom. 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?
Safety, tolerability (time frame: ARQ 197 treatment will be continued until progression of disease, unacceptable toxicity, 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 NCT00612209, 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.