TumorsPhase 1NCT00389480
Study of AR-67 (Formerly DB-67) in Adult Patients With Refractory or Metastatic Solid Malignancies
A Phase 1 study testing AR-67 (formerly DB-67) in people with Tumors, run by Arno Therapeutics at 2 sites in United States.
Trial summary
Hypothesis: AR-67 (formerly DB-67) represents a rationally engineered drug that possesses improved stability, toxicity, and efficacy compared to current Food and Drug Administration (FDA)-approved camptothecins, based on the extensive research of prior studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumors
- What is being tested?
- AR-67 (formerly DB-67)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2006to May 2009
- 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
- >18 year old subjects with solid malignancies that have progressed after at least one prior chemotherapy regimen and have exhausted other therapies
- Treated and clinically stable brain metastases
- Measurable OR non-measurable disease
- Greater than three weeks since surgery
- Normal organ and marrow function
- ECOG Performance Status of < 2
Show all 9Show fewer
- No other prior malignancy except for treated basal cell or squamous cell skin cancer, in situ cervical cancer, Stage I or II cancer (patient in complete remission) or other cancer from which the patient has been disease-free for 5 years.
- Computed tomography (CT) scan of involved areas within 28 days of registration
- Life expectancy of greater than 12 weeks.
Who cannot join
- Pregnant or nursing females
- Chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) of entering the study.
- Patients may not be receiving any other investigational agent. Uncontrolled intercurrent illness including active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Allergic reactions to compounds of similar chemical or biologic composition to DB-67 (i.e. camptothecins such as irinotecan, topotecan, or others of this class of pharmaceuticals).
- Subjects with prior anaphylactic injection reaction of > grade 3 to paclitaxel or any other product formulated with cremophor
- Subjects with HIV
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Kentucky
Lexington, Kentucky, 40536
Arch Medical Services Inc. DBA The Center for Cancer Care and Research
St Louis, Missouri, 63141
About this study
Official title: A Phase I Study of DB-67 (7-t-butyldimethylsilyl-10-hydroxycamptothecin) in Adult Patients With Refractory or Metastatic Solid Malignancies
Hypothesis:
AR-67 (formerly DB-67) represents a rationally engineered drug that possesses improved stability, toxicity, and efficacy compared to current Food and Drug Administration (FDA)-approved camptothecins, based on the extensive research of prior studies. Therefore, the investigators hypothesize that AR-67 (formerly DB-67) will be well-tolerated and efficacious in phase I clinical trials. This initial phase I trial will establish the maximum tolerated dose in humans, establish the toxicity profile, and define the appropriate dose of AR-67 (formerly DB-67) for future phase II and III clinical trials.
Read the detailed description
Overview of Study:
Camptothecins are a potent class of anticancer drugs that inhibit DNA topoisomerase I. Topotecan and irinotecan are two FDA approved second generation congeners currently in clinical use, and have a spectrum of activity which includes colorectal, ovarian, and lung cancers. Unfortunately, these drugs are hampered by a labile α-hydroxy-δ-lactone pharmacophore, which hydrolyzes to yield the inactive carboxylate form of the drug.
AR-67 (formerly DB-67) (7-t-butyldimethylsilyl-10-hydroxycamptothecin) is a third generation analog engineered to be blood stable and highly potent. Its enhanced stability results from two factors: (1) AR-67 (formerly DB-67) is highly lipophilic, partitioning into lipid bilayers, thus protecting it from hydrolysis in the aqueous milieu of the bloodstream, and (2) the 10-hydroxy functionality of the drug effectively ablates the high affinity interactions of the carboxylate drug form with albumin, which has been previously shown to diminish the levels of the active lactone species in the circulation.
On the basis of its stability and activity, AR-67 (formerly DB-67) was selected by the National Cancer Institute (NCI) for development in the first cycle of the Rapid Access to Intervention Development (RAID) program. Data from cycle I, as well as independent data from collaborative efforts, revealed impressive in vitro and in vivo antitumor activity, particularly in an intracranial glioma model system. Through the continued support of the RAID program, the drug has been extensively studied in mice, rats and beagle dogs and the pre-clinical MTD has been determined. After extensive investigation of various formulations, a Cremophor:ethanol compound has been identified as the most appropriate for the phase I study in humans and the GMP grade drug product has been refined and completed. This protocol describes the initial phase I study in humans using AR-67 (formerly DB-67).
Primary Endpoint:
- To estimate the MTD and describe the DLT of intravenous AR-67 (formerly DB-67) administered once daily for 5 days every 21 days to adults with recurrent or refractory solid tumors in which standard therapies are not effective.
Secondary Endpoints:
- To characterize the plasma pharmacokinetics of AR-67 (formerly DB-67) and its metabolites after intravenous administration.
- To explore the pharmacogenetic effects of polymorphisms in drug metabolism and transport mediated by liver enzymes and by efflux or uptake proteins, respectively, and relate these polymorphisms to AR-67 (formerly DB-67) pharmacokinetics and toxicity.
- Conditions
- Tumors
- Being tested
- AR-67 (formerly DB-67)
- Keywords
- Solid Tumors, Solid Malignancies, Phase I
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AR-67 (formerly DB-67)Drug
infusion daily x 5 days, every 21 days
| Study group | Role | What they receive |
|---|---|---|
| I | Experimental | Dose escalating Receives: Drug: AR-67 (formerly DB-67) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
Measured: Any time during the four 21-day cycles
Dose limiting toxicity (DLT)
Measured: Any time during the four 21-day cycles
Secondary outcomes (2)
Pharmacokinetics
Measured: at each dose during week 1
Pharmacogenetic effects of polymorphisms
Measured: at each dose during week 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2006 (estimated)
- Study startOct 2006
- Primary completionFeb 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arno Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Kentucky, Arch Medical Services Inc., DBA The Center for Cancer Care and Research
- Investigators
- Susanne Arnold, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00389480
- Sponsor's protocol ID
- ARN-AR67-CT101
- Status last verified
- Aug 2009
- First submitted
- 17 Oct 2006
- Last updated
- 11 Aug 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of DB-67 (7-t-butyldimethylsilyl-10-hydroxycamptothecin) in Adult Patients With Refractory or Metastatic Solid Malignancies
- ClinicalTrials.gov ID
- NCT00389480
- Acronym / sponsor ID
- ARN-AR67-CT101
- Conditions
- Tumors
- Keywords
- Solid Tumors, Solid Malignancies, Phase I
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Arno TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- University of Kentucky, Arch Medical Services Inc., DBA The Center for Cancer Care and Research
- Study start
- Oct 2006
- Primary completion
- Feb 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 18 Oct 2006 (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.
Hypothesis:
AR-67 (formerly DB-67) represents a rationally engineered drug that possesses improved stability, toxicity, and efficacy compared to current Food and Drug Administration (FDA)-approved camptothecins, based on the extensive research of prior studies. Therefore, the investigators hypothesize that AR-67 (formerly DB-67) will be well-tolerated and efficacious in phase I clinical trials. This initial phase I trial will establish the maximum tolerated dose in humans, establish the toxicity profile, and define the appropriate dose of AR-67 (formerly DB-67) for future phase II and III clinical trials.
Detailed description
Overview of Study:
Camptothecins are a potent class of anticancer drugs that inhibit DNA topoisomerase I. Topotecan and irinotecan are two FDA approved second generation congeners currently in clinical use, and have a spectrum of activity which includes colorectal, ovarian, and lung cancers. Unfortunately, these drugs are hampered by a labile α-hydroxy-δ-lactone pharmacophore, which hydrolyzes to yield the inactive carboxylate form of the drug.
AR-67 (formerly DB-67) (7-t-butyldimethylsilyl-10-hydroxycamptothecin) is a third generation analog engineered to be blood stable and highly potent. Its enhanced stability results from two factors: (1) AR-67 (formerly DB-67) is highly lipophilic, partitioning into lipid bilayers, thus protecting it from hydrolysis in the aqueous milieu of the bloodstream, and (2) the 10-hydroxy functionality of the drug effectively ablates the high affinity interactions of the carboxylate drug form with albumin, which has been previously shown to diminish the levels of the active lactone species in the circulation.
On the basis of its stability and activity, AR-67 (formerly DB-67) was selected by the National Cancer Institute (NCI) for development in the first cycle of the Rapid Access to Intervention Development (RAID) program. Data from cycle I, as well as independent data from collaborative efforts, revealed impressive in vitro and in vivo antitumor activity, particularly in an intracranial glioma model system. Through the continued support of the RAID program, the drug has been extensively studied in mice, rats and beagle dogs and the pre-clinical MTD has been determined. After extensive investigation of various formulations, a Cremophor:ethanol compound has been identified as the most appropriate for the phase I study in humans and the GMP grade drug product has been refined and completed. This protocol describes the initial phase I study in humans using AR-67 (formerly DB-67).
Primary Endpoint:
- To estimate the MTD and describe the DLT of intravenous AR-67 (formerly DB-67) administered once daily for 5 days every 21 days to adults with recurrent or refractory solid tumors in which standard therapies are not effective.
Secondary Endpoints:
- To characterize the plasma pharmacokinetics of AR-67 (formerly DB-67) and its metabolites after intravenous administration.
- To explore the pharmacogenetic effects of polymorphisms in drug metabolism and transport mediated by liver enzymes and by efflux or uptake proteins, respectively, and relate these polymorphisms to AR-67 (formerly DB-67) pharmacokinetics and toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| I | Experimental | Drug: AR-67 (formerly DB-67)Dose escalating |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- >18 year old subjects with solid malignancies that have progressed after at least one prior chemotherapy regimen and have exhausted other therapies
- Treated and clinically stable brain metastases
- Measurable OR non-measurable disease
- Greater than three weeks since surgery
- Normal organ and marrow function
Key exclusion criteria (6 listed)
- Pregnant or nursing females
- Chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) of entering the study.
- Patients may not be receiving any other investigational agent. Uncontrolled intercurrent illness including active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Allergic reactions to compounds of similar chemical or biologic composition to DB-67 (i.e. camptothecins such as irinotecan, topotecan, or others of this class of pharmaceuticals).
- Subjects with prior anaphylactic injection reaction of > grade 3 to paclitaxel or any other product formulated with cremophor
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-67 (formerly DB-67)infusion daily x 5 days, every 21 days | Drug | I |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: Any time during the four 21-day cycles
Dose limiting toxicity (DLT)
Time frame: Any time during the four 21-day cycles
2 secondary outcomes
Pharmacokinetics
Time frame: at each dose during week 1
Pharmacogenetic effects of polymorphisms
Time frame: at each dose during week 1
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 11 Aug 2009.
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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.
Susanne Arnold, MD principal investigator
University of Kentucky
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AR-67 (formerly DB-67) in people with Tumors, run by Arno Therapeutics 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 9 inclusion and 6 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 11 Aug 2009. 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?
Maximum tolerated dose (MTD) (time frame: Any time during the four 21-day cycles). The study lists 2 primary outcomes in all. 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 11 Aug 2009.