Solid TumorPhase 1NCT01225536
Dose Escalation Study of ARQ 736 in Adult Subjects With Advanced Solid Tumors Harboring BRAF and/or NRAS Mutations
A Phase 1 study testing ARQ 736 in people with Solid Tumor, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 4 sites in 2 countries.
Trial summary
This is an open-label, Phase 1, dose escalation study of oral ARQ 736 administered to subjects with advanced solid tumors harboring the mutation. The study is designed to explore the safety, tolerability, pharmacokinetics and pharmacodynamics of ARQ 736 and to define a recommended Phase 2 dose of ARQ 736. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- ARQ 736
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Oct 2010to Mar 2013
- 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 granted prior to initiation of any study-specific procedures
- Male or female subjects of ≥ 18 years of age
- All subjects must be positive for a BRAF and/or NRAS mutation
- Histologically or cytologically confirmed locally advanced, inoperable or metastatic solid tumors
- Failure to respond to at least one prior systemic therapy (including previous treatment with BRAF inhibitors) or to whom standard or curative therapy does not exist
- Life expectancy of greater than three months
Show all 18Show fewer
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
- Hemoglobin (Hgb) ≥10 g/dl
- Absolute neutrophil count (ANC) ≥1.5 x 10^9/L
- Platelet count ≥100 x 10^9/L
- Total bilirubin ≤1.5 × upper limit of normal (ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × ULN (≤5 x ULN for subjects with liver metastases)
- Serum creatinine ≤1.5 × ULN or creatinine clearance >60 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal
- Left Ventricular Ejection Fraction (LVEF) ≥ the institutional lower limit normal (ILLN)
- Male or female subjects of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception or avoidance of intercourse during the study and for 30 days after the last dose of ARQ 736
- Females of childbearing potential must have a negative serum pregnancy test within seven days prior to the first dose of ARQ 736
- Must agree to have tumor and/or skin (nevi) biopsy at baseline and on Day 15 or Day 22 of Cycle 1. Tumor biopsy will be done if the subject has a lesion for which in the Investigator's opinion a non- or minimally invasive tumor biopsy may be performed. If tumor biopsy is not available, skin (nevi) biopsy should be performed.
Who cannot join
- Anti-cancer chemotherapy, immunotherapy, or investigational agents within four weeks of the first dose of ARQ 736
- Major surgery or radiotherapy within two weeks of the first dose of ARQ 736
- Brain metastases that are progressing or have been documented to be stable for less than six weeks, or for which systemic corticosteroids are required
- History of allergic reactions attributed to compounds of similar chemical or biologic composition as ARQ 736
- Unable or unwilling to swallow the complete daily dose of ARQ 736
- Significant gastrointestinal disorder(s), in the opinion of the Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
Show all 13Show fewer
- History of myocardial infarction (MI) within 6 months of the administration of the first dose of ARQ 736 (MI occurring > 6 months of the first dose of ARQ 736 will be permitted)
- History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification within 6 months of the administration of the first dose of ARQ 736
- Previous malignancy within 2 years of the first dose of ARQ 736, except carcinoma in-situ of the cervix
- Concurrent uncontrolled illness, including but not limited to:
- Ongoing or active infection, including human immunodeficiency virus (HIV) infection or bleeding
- Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements
- Blood transfusion within five days prior to blood draw being used to confirm eligibility
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
Study site
Los Angeles, California, 90025
Study site
New Brunswick, New Jersey, 08903
Study site
New Haven, Connecticut, 06520
About this study
Official title: A Phase 1 Dose Escalation Study of ARQ 736 in Adult Subjects With Advanced Solid Tumors Harboring BRAF and/or NRAS Mutations
This is an open-label, Phase 1, dose escalation study of oral ARQ 736 administered to subjects with advanced solid tumors harboring the mutation. The study is designed to explore the safety, tolerability, pharmacokinetics and pharmacodynamics of ARQ 736 and to define a recommended Phase 2 dose of ARQ 736.
Read the detailed description
Treatment will be initiated at a dose level of 450 mg twice daily (900 mg/daily). All cycles/cohorts of therapy will consist of the oral administration of ARQ 736 twice or four times a day, one hour prior to or two hours after the meal for 28 days continuously. Tumor assessments (CT scan or MRI) will be performed at Baseline, and every two cycles (every eight weeks) thereafter or as otherwise clinically indicated. For early assessment of evidence of biological activity of the tumor PET scan may be performed at Baseline and four weeks from the administration of the first dose of ARQ 736 (approximately Cycle 2 Day1).
- Conditions
- Solid Tumor
- Being tested
- ARQ 736
- Keywords
- BRAF mutations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARQ 736Drug
Subjects in this study will receive ARQ 736 orally at dose levels specified for their respective dose cohorts. Dosing will begin at 900 mg/day (first cohort) and escalate until the recommended Phase 2 dose or maximum tolerated dose is determined. Cycles will be repeated in four-week (28-day) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted.
| Study group | Role | What they receive |
|---|---|---|
| ARQ 736 | Experimental | Not described Receives: Drug: ARQ 736 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess safety and tolerability of study drug in subjects with advanced solid tumors who have BRAF and/or NRAS mutations
Measured: Up to treatment discontinuation + 30 days with an estimated treatment duration of 24 weeks
Secondary outcomes (4)
Assess pharmacokinetic profile
Measured: During first cycle of treatment (28 days)
Assess pharmacodynamic activity
Measured: During first cycle of treatment (28 days) plus Day 1 of each consecutive cycle with an estimated treatment duration of 24 weeks
Determine preliminary evidence of activity
Measured: Up to treatment discontinuation with an estimated treatment duration of 24 weeks
Determine recommended Phase 2 dose
Measured: Up to treatment discontinuation with an estimated treatment duration of 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionJan 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01225536
- Sponsor's protocol ID
- ARQ 736-101
- Status last verified
- May 2013
- First submitted
- 20 Oct 2010
- Last updated
- 3 May 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation Study of ARQ 736 in Adult Subjects With Advanced Solid Tumors Harboring BRAF and/or NRAS Mutations
- ClinicalTrials.gov ID
- NCT01225536
- Acronym / sponsor ID
- ARQ 736-101
- Conditions
- Solid Tumor
- Keywords
- BRAF mutations
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 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
- Oct 2010
- Primary completion
- Jan 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 21 Oct 2010 (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, Phase 1, dose escalation study of oral ARQ 736 administered to subjects with advanced solid tumors harboring the mutation. The study is designed to explore the safety, tolerability, pharmacokinetics and pharmacodynamics of ARQ 736 and to define a recommended Phase 2 dose of ARQ 736.
Detailed description
Treatment will be initiated at a dose level of 450 mg twice daily (900 mg/daily). All cycles/cohorts of therapy will consist of the oral administration of ARQ 736 twice or four times a day, one hour prior to or two hours after the meal for 28 days continuously. Tumor assessments (CT scan or MRI) will be performed at Baseline, and every two cycles (every eight weeks) thereafter or as otherwise clinically indicated. For early assessment of evidence of biological activity of the tumor PET scan may be performed at Baseline and four weeks from the administration of the first dose of ARQ 736 (approximately Cycle 2 Day1).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ARQ 736 | Experimental | Drug: ARQ 736 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Signed written informed consent granted prior to initiation of any study-specific procedures
- Male or female subjects of ≥ 18 years of age
- All subjects must be positive for a BRAF and/or NRAS mutation
- Histologically or cytologically confirmed locally advanced, inoperable or metastatic solid tumors
- Failure to respond to at least one prior systemic therapy (including previous treatment with BRAF inhibitors) or to whom standard or curative therapy does not exist
Key exclusion criteria (13 listed)
- Anti-cancer chemotherapy, immunotherapy, or investigational agents within four weeks of the first dose of ARQ 736
- Major surgery or radiotherapy within two weeks of the first dose of ARQ 736
- Brain metastases that are progressing or have been documented to be stable for less than six weeks, or for which systemic corticosteroids are required
- History of allergic reactions attributed to compounds of similar chemical or biologic composition as ARQ 736
- Unable or unwilling to swallow the complete daily dose of ARQ 736
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 736Subjects in this study will receive ARQ 736 orally at dose levels specified for their respective dose cohorts. Dosing will begin at 900 mg/day (first cohort) and escalate until the recommended Phase 2 dose or maximum tolerated dose is determined. Cycles will be repeated in four-week (28-day) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted. | Drug | ARQ 736 |
Primary outcome
Assess safety and tolerability of study drug in subjects with advanced solid tumors who have BRAF and/or NRAS mutations
Time frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 24 weeks
4 secondary outcomes
Assess pharmacokinetic profile
Time frame: During first cycle of treatment (28 days)
Assess pharmacodynamic activity
Time frame: During first cycle of treatment (28 days) plus Day 1 of each consecutive cycle with an estimated treatment duration of 24 weeks
Determine preliminary evidence of activity
Time frame: Up to treatment discontinuation with an estimated treatment duration of 24 weeks
Determine recommended Phase 2 dose
Time frame: Up to treatment discontinuation with an estimated treatment duration of 24 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 May 2013.
Related trials for Solid Tumor
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
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ARQ 736 in people with Solid Tumor, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 4 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 18 inclusion and 13 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 May 2013. 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, Italy. 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?
Assess safety and tolerability of study drug in subjects with advanced solid tumors who have BRAF and/or NRAS mutations (time frame: Up to treatment discontinuation + 30 days with an estimated treatment duration of 24 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 May 2013.