Solid TumorsPhase 1NCT00978523
Study of AR-12 (2-Amino-N-[4-[5-(2 Phenanthrenyl)-3-(Trifluoromethyl)-1H-pyrazol-1-yl] Phenyl]-Acetamide) in Adult Patients With Advanced or Recurrent Solid Tumors or Lymphoma
A Phase 1 study testing AR-12: (2-Amino-N-[4-[5-(2 phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] phenyl]-acetamide) in people with Solid Tumors and Lymphoma, run by Arno Therapeutics at 3 sites in 2 countries.
Trial summary
The primary objective of this study in adults with advanced or recurrent solid tumors or lymphoma is to evaluate the safety and tolerability of AR-12 by describing dose-limiting toxicities (DLTs), and thereby establishing the maximum tolerated dose (MTD) or, in the absence of reaching an MTD, a recommended dose (RD)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Lymphoma
- What is being tested?
- AR-12: (2-Amino-N-[4-[5-(2 phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] phenyl]-acetamide)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Aug 2009to Nov 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 must be obtained and documented according to International Conference on Harmonisation (ICH) Good Clinical Practice (GCP), the local regulatory requirements, and the permission to use private health information in accordance with the Health Insurance Portability and Accountability Act (HIPAA) prior to study-specific Screening procedures.
- Both men and women and members of all races and ethnic groups are eligible for this trial.
- Patients must be 18 years of age or greater.
- Patients must have a histologically or cytologically confirmed advanced or recurrent solid tumor or lymphoma for which standard curative or palliative measures do not exist or are no longer effective. Patients who have recurrent disease after previous surgery, radiation therapy, and/or chemotherapy are eligible. No restriction is placed on the number of prior therapies. At least 4 weeks must have elapsed since the completion of prior therapy, including major surgery, and patients must have recovered from all associated toxicities no greater than grade 1 at the time of Screening. Patients with prostate cancer must have discontinued anti-androgens (eg, bicalutamide, nilutamide) for at least 6 weeks; chemical castration with LHRH analogues can be continued.
- Patients must have measurable or evaluable disease or disease that otherwise meets criteria for treatment and can be followed by an acceptable biomarker (eg, PSA or CA-125) documented within 28 days of starting treatment with AR-12. Pleural effusions, ascites, bony metastasis, and laboratory parameters are not acceptable as the only evidence of disease.
- Patients must have acceptable organ and marrow function documented within 7 days of registration, defined as follows:
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- Leukocytes >3,000/mcL
- Absolute neutrophil count >1,500/mcL
- Platelets ≥150,000/mcL
- Fasting blood glucose Within normal institutional limits
- Total bilirubin Within normal institutional limits
- AST/ALT <2.5 X institutional ULN; <5 X ULN in presence of liver metastasis
- Creatinine Within normal institutional limits, OR
- Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Patients must have an ECOG performance status of 0 or 1.
- Patients must have adequate pulmonary function (no more than a grade 2 finding per CTCAE version 3) and oxygen saturation ≥93% on room air, measured within 14 days prior to initiation of treatment with AR-12.
- All patients who are sexually active must use a medically acceptable, as judged by the investigator, and highly effective method of birth control for the duration of the study and to continue for 30 days after the last AR-12 dose. A highly effective method of birth control is defined as any method that results in a low failure rate, including implants, injectables, some intrauterine devices, sexual abstinence, and surgical sterilization (eg, vasectomy, tubal ligation, hysterectomy). Women of childbearing potential must have a negative serum pregnancy test documented within 7 days prior to Day 0. Furthermore, male study patients must also not donate sperm from Study Day 1 until 90 days after the end of treatment.
- Patients must have a life expectancy of greater than 12 weeks.
Who cannot join
- Patients must not have had chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Patients who have received prior chemotherapy must have recovered to no greater than grade 1 from all AEs/toxicities (except alopecia) due to prior agents.
- Patients with a history of insulin- or non-insulin-dependent diabetes requiring antidiabetic medication.
- Patients requiring treatment with anticoagulants.
- Patients requiring chronic corticosteroids (dose equivalent ≥20 mg prednisolone).
- Patients requiring chronic Celebrex® (celecoxib) therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition (eg, celecoxib).
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- Patients who are unable or unwilling to swallow AR-12 capsules daily or who have any concurrent medical condition that may impact drug absorption, including a history suggestive of intermittent tumor-associated bowel obstruction, and partial small bowel resection.
- Patients with known or symptomatic brain metastases (including leptomeningeal disease). Patients with asymptomatic, treated brain metastases are allowed. Patients with primary brain tumors will be allowed in the MTD expansion cohort; however, radiotherapy must have been completed ≥90 days prior to Screening.
- Patients with any other prior malignancy are not allowed except for the following:
- Adequately treated basal cell or squamous cell skin cancer
- In situ cervical cancer
- Adequately treated Stage I or II cancer from which the patient is currently in complete remission or other cancer from which the patient has been disease-free for 2 years
- Patients may have had prior palliative radiation therapy; however, radiation must not have been to more than 15% of marrow-producing locations.
- Pregnant women are excluded from this study because the potential for teratogenic or abortifacient effects of AR-12 are not known. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with AR-12, breastfeeding should be discontinued if the mother is treated with AR-12.
- Patients with known human immunodeficiency virus (HIV) are not eligible for this study.
- 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.
- Patients with QTc > 470 msec on Screening ECG or a clinically relevant ECG abnormality as determined by the investigator or his/her designee.
- Patients with left bundle-branch block.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
The Ohio State University - Comprehensive Cancer Center
Columbus, Ohio, 43210
TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona, 85258
About this study
Official title: A Phase 1 Study of AR-12 (2-Amino-N-[4-[5-(2 Phenanthrenyl)-3-(Trifluoromethyl)-1H-pyrazol-1-yl] Phenyl]-Acetamide) in Adult Patients With Advanced or Recurrent Solid Tumors or Lymphoma, for Which No Standard Therapy Is Available
The primary objective of this study in adults with advanced or recurrent solid tumors or lymphoma is to evaluate the safety and tolerability of AR-12 by describing dose-limiting toxicities (DLTs), and thereby establishing the maximum tolerated dose (MTD) or, in the absence of reaching an MTD, a recommended dose (RD) for additional study of oral AR-12 administered daily in cycles of 28 days (28 consecutive days of once daily treatment with at least a 7-day break between the first and second treatment cycles and recovery of toxicity to grade 1 or less, with no planned off-treatment days between subsequent cycles).
Read the detailed description
This is a single-agent, open-label, Phase 1, dose-escalation study in adult patients with advanced or recurrent solid tumors or lymphoma. Patients will receive orally administered AR-12 once daily for 28 consecutive days. The first dosing cycle will be followed by at least a 7 day off-treatment period; however, no off-treatment period will be scheduled between subsequent treatment cycles. If daily dosing is not tolerated by the study population, alternative dosing schedules may be pursued (eg, 21 consecutive days of dosing followed by 7 days off treatment), as indicated by the safety, pharmacokinetic, and pharmacodynamic data; all changes to the protocol-specified dosing schedule must be agreed upon by the investigators and the medical monitor. If individual patients respond to AR-12 treatment with an objective response or stable disease according to RECIST criteria and meet pre-specified retreatment criteria, they may continue to receive cycles of AR-12 in the absence of untoward or serious toxicity; however, no patient is permitted to start a subsequent cycle after each bi-monthly disease evaluation until it is confirmed that disease progression has not occurred.
- Conditions
- Solid Tumors, Lymphoma
- Being tested
- AR-12: (2-Amino-N-[4-[5-(2 phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] phenyl]-acetamide)
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AR-12: (2-Amino-N-[4-[5-(2 phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] phenyl]-acetamide)Drug
Oral, dose-escalation
| Study group | Role | What they receive |
|---|---|---|
| Treatment with AR-12 | Experimental | This is a single-agent, open-label, Phase 1, dose-escalation study in adult patients with advanced or recurrent solid tumors or lymphoma. Patients will receive orally administered AR-12 once daily for 28 consecutive days. The first dosing cycle will be followed by at least a 7 day off-treatment period; however, no off-treatment period will be scheduled between subsequent treatment cycles Receives: Drug: AR-12: (2-Amino-N-[4-[5-(2 phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] phenyl]-acetamide) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of this study in adults with advanced or recurrent solid tumors or lymphoma is to evaluate the safety and tolerability of AR-12.
Measured: Every 2 Cycles (approximately 28 days per cycle)
Secondary outcomes (1)
Evaluate PK samples during C1, identify and use biomarkers to characterize the PD effects in surrogate and tumor tissue, establish a biologically active dose range, assess preliminary anti-tumor activity in cancer patients.
Measured: C1 only in each dose cohort
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2009 (estimated)
- Study startAug 2009
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arno Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James P Thomas, MD PhD, Principal investigator, The Ohio State University Comprehensive Cancer CenterRaoul Tibes, MD PhD, Principal investigator, TGen Clinical Research Services at Scottsdale HealthcareJohann S de Bono, MD PhD, Principal investigator, Royal Marsden Hospital - Drug Development Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00978523
- Sponsor's protocol ID
- ARN-AR12-CT101
- Status last verified
- Jan 2014
- First submitted
- 15 Sep 2009
- Last updated
- 29 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of AR-12 (2-Amino-N-[4-[5-(2 Phenanthrenyl)-3-(Trifluoromethyl)-1H-pyrazol-1-yl] Phenyl]-Acetamide) in Adult Patients With Advanced or Recurrent Solid Tumors or Lymphoma, for Which No Standard Therapy Is Available
- ClinicalTrials.gov ID
- NCT00978523
- Acronym / sponsor ID
- ARN-AR12-CT101
- Conditions
- Solid Tumors, Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Arno TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Aug 2009
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 17 Sep 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.
The primary objective of this study in adults with advanced or recurrent solid tumors or lymphoma is to evaluate the safety and tolerability of AR-12 by describing dose-limiting toxicities (DLTs), and thereby establishing the maximum tolerated dose (MTD) or, in the absence of reaching an MTD, a recommended dose (RD) for additional study of oral AR-12 administered daily in cycles of 28 days (28 consecutive days of once daily treatment with at least a 7-day break between the first and second treatment cycles and recovery of toxicity to grade 1 or less, with no planned off-treatment days between subsequent cycles).
Detailed description
This is a single-agent, open-label, Phase 1, dose-escalation study in adult patients with advanced or recurrent solid tumors or lymphoma. Patients will receive orally administered AR-12 once daily for 28 consecutive days. The first dosing cycle will be followed by at least a 7 day off-treatment period; however, no off-treatment period will be scheduled between subsequent treatment cycles. If daily dosing is not tolerated by the study population, alternative dosing schedules may be pursued (eg, 21 consecutive days of dosing followed by 7 days off treatment), as indicated by the safety, pharmacokinetic, and pharmacodynamic data; all changes to the protocol-specified dosing schedule must be agreed upon by the investigators and the medical monitor. If individual patients respond to AR-12 treatment with an objective response or stable disease according to RECIST criteria and meet pre-specified retreatment criteria, they may continue to receive cycles of AR-12 in the absence of untoward or serious toxicity; however, no patient is permitted to start a subsequent cycle after each bi-monthly disease evaluation until it is confirmed that disease progression has not occurred.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with AR-12 | Experimental | Drug: AR-12: (2-Amino-N-[4-[5-(2 phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] phenyl]-acetamide)This is a single-agent, open-label, Phase 1, dose-escalation study in adult patients with advanced or recurrent solid tumors or lymphoma. Patients will receive orally administered AR-12 once daily for 28 consecutive days. The first dosing cycle will be followed by at least a 7 day off-treatment period; however, no off-treatment period will be scheduled between subsequent treatment cycles |
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 must be obtained and documented according to International Conference on Harmonisation (ICH) Good Clinical Practice (GCP), the local regulatory requirements, and the permission to use private health information in accordance with the Health Insurance Portability and Accountability Act (HIPAA) prior to study-specific Screening procedures.
- Both men and women and members of all races and ethnic groups are eligible for this trial.
- Patients must be 18 years of age or greater.
- Patients must have a histologically or cytologically confirmed advanced or recurrent solid tumor or lymphoma for which standard curative or palliative measures do not exist or are no longer effective. Patients who have recurrent disease after previous surgery, radiation therapy, and/or chemotherapy are eligible. No restriction is placed on the number of prior therapies. At least 4 weeks must have elapsed since the completion of prior therapy, including major surgery, and patients must have recovered from all associated toxicities no greater than grade 1 at the time of Screening. Patients with prostate cancer must have discontinued anti-androgens (eg, bicalutamide, nilutamide) for at least 6 weeks; chemical castration with LHRH analogues can be continued.
- Patients must have measurable or evaluable disease or disease that otherwise meets criteria for treatment and can be followed by an acceptable biomarker (eg, PSA or CA-125) documented within 28 days of starting treatment with AR-12. Pleural effusions, ascites, bony metastasis, and laboratory parameters are not acceptable as the only evidence of disease.
Key exclusion criteria (18 listed)
- Patients must not have had chemotherapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Patients who have received prior chemotherapy must have recovered to no greater than grade 1 from all AEs/toxicities (except alopecia) due to prior agents.
- Patients with a history of insulin- or non-insulin-dependent diabetes requiring antidiabetic medication.
- Patients requiring treatment with anticoagulants.
- Patients requiring chronic corticosteroids (dose equivalent ≥20 mg prednisolone).
- Patients requiring chronic Celebrex® (celecoxib) therapy.
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 |
|---|---|---|
| AR-12: (2-Amino-N-[4-[5-(2 phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] phenyl]-acetamide)Oral, dose-escalation | Drug | Treatment with AR-12 |
Primary outcome
The primary objective of this study in adults with advanced or recurrent solid tumors or lymphoma is to evaluate the safety and tolerability of AR-12.
Time frame: Every 2 Cycles (approximately 28 days per cycle)
1 secondary outcome
Evaluate PK samples during C1, identify and use biomarkers to characterize the PD effects in surrogate and tumor tissue, establish a biologically active dose range, assess preliminary anti-tumor activity in cancer patients.
Time frame: C1 only in each dose cohort
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 29 Jan 2014.
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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.
James P Thomas, MD PhD principal investigator
The Ohio State University Comprehensive Cancer Center
Raoul Tibes, MD PhD principal investigator
TGen Clinical Research Services at Scottsdale Healthcare
Johann S de Bono, MD PhD principal investigator
Royal Marsden Hospital - Drug Development Unit
3 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 AR-12: (2-Amino-N-[4-[5-(2 phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] phenyl]-acetamide) in people with Solid Tumors and Lymphoma, run by Arno Therapeutics at 3 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 18 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 29 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, 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?
The primary objective of this study in adults with advanced or recurrent solid tumors or lymphoma is to evaluate the safety and tolerability of AR-12. (time frame: Every 2 Cycles (approximately 28 days per cycle)). 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 29 Jan 2014.