Non-Hodgkins LymphomaPhase 1NCT00443976
Aurora Kinase Inhibitor AT9283 in Treating Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma
A Phase 1 study testing Aurora kinase inhibitor AT9283 in people with Non-Hodgkins Lymphoma and Unspecified Adult Solid Tumor, Protocol Specific, run by NCIC Clinical Trials Group at 2 sites in Canada.
Trial summary
RATIONALE: Aurora kinase inhibitor AT9283 (AT9283) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of AT9283 in treating patients with advanced or metastatic solid tumors or non-Hodgkin's lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkins Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- Aurora kinase inhibitor AT9283
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesCanada
- Study dates
- 30 Jan 2007to 6 Jan 2012
- 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
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed diagnosis of 1 of the following:
- Advanced and/or metastatic solid tumor
- Advanced or metastatic non-Hodgkin's lymphoma refractory to standard therapy
- Clinically or radiologically documented disease
- No tumor marker elevation as only evidence of disease
- No untreated brain or meningeal metastases
- Treated and stable brain metastases allowed provided they are asymptomatic and do not require steroids
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Absolute granulocyte count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Creatinine ≤ 1.25 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min
- Bilirubin normal
- ALT and AST ≤ 2 times ULN (≤5 times ULN if liver metastases are present)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use two effective methods of contraception
- No untreated or uncontrolled hypertension, cardiovascular conditions, or symptomatic cardiac dysfunction
- No active or uncontrolled infections
- No serious illness or medical condition that would preclude study treatment
PRIOR CONCURRENT THERAPY:
- At least 2 weeks since prior major surgery and recovered
- At least 3 weeks since prior palliative radiotherapy and recovered
- Low-dose, nonmyelosuppressive radiotherapy may be allowed
- At least 3 weeks since prior chemotherapy for solid tumors and recovered
- No more than 2 prior cytotoxic chemotherapy regimens for metastatic disease
- At least 4 weeks since prior steroids
- No limitations on prior therapy for patients with non-Hodgkin's lymphoma
- Prior hormonal, immunologic, biologic or signal transduction inhibitor therapy allowed
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Ottawa Health Research Institute - General Division
Ottawa, Ontario, K1H 8L6
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: A Phase I Study of AT9283 Given As a 24 Hour Infusion on Days 1 and 8 Every Three Weeks in Patients With Advanced Incurable Malignancy
RATIONALE: Aurora kinase inhibitor AT9283 (AT9283) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of AT9283 in treating patients with advanced or metastatic solid tumors or non-Hodgkin's lymphoma.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose and recommended phase II dose of Aurora kinase inhibitor AT9283 (AT9283) in patients with incurable advanced or metastatic solid tumors or non-Hodgkin's lymphoma.
- Determine the safety, tolerability, toxicity profile, dose-limiting toxicity, and pharmacokinetic profile of this drug in these patients.
- Correlate the toxicity profile with the pharmacokinetics of this drug in these patients.
- Assess, preliminarily, evidence of antitumor activity of this drug in these patients.
- Determine the pharmacodynamic activity of this drug in these patients and correlate with biological endpoints.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive Aurora kinase inhibitor AT9283 (AT9283) IV over 24 hours on days 1 and 8 . Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of AT9283 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The dose preceding the MTD is the recommended phase II dose (RPTD). Up to 8 additional patients are treated at the RPTD.
Patients treated at the RPTD undergo skin and tumor tissue biopsy and blood collection at baseline and on days 2 and/or 3. Samples are examined by pharmacokinetic and pharmacodynamic analysis, including immunohistochemistry, immunocytochemistry, western blotting, immunoenzyme techniques, flow cytometry, and reverse transcriptase-polymerase chain reaction, for biological markers.
After completion of study treatment, patients are followed at 4 weeks and then every 3 months until disease progression.
PROJECTED ACCRUAL: Up to 30 patients will be accrued for this study.
- Being tested
- Aurora kinase inhibitor AT9283
- Keywords
- unspecified adult solid tumor, protocol specific, recurrent adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 2 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage IV adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin, Burkitt Lymphoma, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aurora kinase inhibitor AT9283Drug
The starting dose of AT9283 will be 1.5 mg/m2 given as a 24 hour IV infusion on Days 1 and 8 every three weeks.
| Study group | Role | What they receive |
|---|---|---|
| AT9283 | Experimental | Not described Receives: Drug: Aurora kinase inhibitor AT9283 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283)
Doses escalated as described in protocol section 4.3. MTD defined as that dose at which ≥ 2/6 or ≥ 2/3 patients experience DLT (as defined in protocol section 4.4).
Measured: 1 year
Recommended phase II dose of AT9283
RPTD defined as one dose lower than MTD.
Measured: 1 year
Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283
Adverse events graded using NCI CTCAE V3.0
Measured: every 3 weeks
Pharmacokinetic profile of AT9283
PK samples collected on all patients during cycle 1 as described in protocol section 17.2.
Measured: cycle one only
Secondary outcomes (1)
Efficacy of AT9283
All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10.
Measured: every 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2007 (estimated)
- Study start30 Jan 2007
- Primary completion9 Apr 2010
- Study completion6 Jan 2012
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 Non-Hodgkins LymphomaStudies 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
- NCIC Clinical Trials Group
- Sponsor type
- Research network
- Collaborators
- Astex Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Karen A. Gelmon, MD, Study chair, British Columbia Cancer AgencySusan F. Dent, MD, Study chair, Ottawa Regional Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00443976
- Sponsor's protocol ID
- I181
- Other IDs
- CDR0000523837, CAN-NCIC-IND181, ASTEX-CAN-NCIC-IND181
- Status last verified
- Apr 2020
- First submitted
- 5 Mar 2007
- Last updated
- 4 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dent SF, Gelmon KA, Chi KN, Jonker DJ, Wainman N, Capier CA, Chen EX, Lyons JF, Seymour L. NCIC CTG IND.181: phase I study of AT9283 given as a weekly 24 hour infusion in advanced malignancies. Invest New Drugs. 2013 Dec;31(6):1522-9. doi: 10.1007/s10637-013-0018-9. Epub 2013 Sep 27.
PubMed 24072436
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of AT9283 Given As a 24 Hour Infusion on Days 1 and 8 Every Three Weeks in Patients With Advanced Incurable Malignancy
- ClinicalTrials.gov ID
- NCT00443976
- Acronym / sponsor ID
- I181
- Keywords
- unspecified adult solid tumor, protocol specific, recurrent adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 2 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- NCIC Clinical Trials GroupResearch network
- Collaborators
- Astex Pharmaceuticals, Inc.
- Study start
- 30 Jan 2007 (actual)
- Primary completion
- 9 Apr 2010 (actual)
- Study completion
- 6 Jan 2012 (actual)
- First posted
- 7 Mar 2007 (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.
RATIONALE: Aurora kinase inhibitor AT9283 (AT9283) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of AT9283 in treating patients with advanced or metastatic solid tumors or non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose and recommended phase II dose of Aurora kinase inhibitor AT9283 (AT9283) in patients with incurable advanced or metastatic solid tumors or non-Hodgkin's lymphoma.
- Determine the safety, tolerability, toxicity profile, dose-limiting toxicity, and pharmacokinetic profile of this drug in these patients.
- Correlate the toxicity profile with the pharmacokinetics of this drug in these patients.
- Assess, preliminarily, evidence of antitumor activity of this drug in these patients.
- Determine the pharmacodynamic activity of this drug in these patients and correlate with biological endpoints.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive Aurora kinase inhibitor AT9283 (AT9283) IV over 24 hours on days 1 and 8 . Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of AT9283 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The dose preceding the MTD is the recommended phase II dose (RPTD). Up to 8 additional patients are treated at the RPTD.
Patients treated at the RPTD undergo skin and tumor tissue biopsy and blood collection at baseline and on days 2 and/or 3. Samples are examined by pharmacokinetic and pharmacodynamic analysis, including immunohistochemistry, immunocytochemistry, western blotting, immunoenzyme techniques, flow cytometry, and reverse transcriptase-polymerase chain reaction, for biological markers.
After completion of study treatment, patients are followed at 4 weeks and then every 3 months until disease progression.
PROJECTED ACCRUAL: Up to 30 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AT9283 | Experimental | Drug: Aurora kinase inhibitor AT9283 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Aurora kinase inhibitor AT9283The starting dose of AT9283 will be 1.5 mg/m2 given as a 24 hour IV infusion on Days 1 and 8 every three weeks. | Drug | AT9283 |
Primary outcome
Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283)
Time frame: 1 year
Doses escalated as described in protocol section 4.3. MTD defined as that dose at which ≥ 2/6 or ≥ 2/3 patients experience DLT (as defined in protocol section 4.4).
Recommended phase II dose of AT9283
Time frame: 1 year
RPTD defined as one dose lower than MTD.
Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283
Time frame: every 3 weeks
Adverse events graded using NCI CTCAE V3.0
Pharmacokinetic profile of AT9283
Time frame: cycle one only
PK samples collected on all patients during cycle 1 as described in protocol section 17.2.
1 secondary outcome
Efficacy of AT9283
Time frame: every 6 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 4 Aug 2023.
- Results publication: PubMed 24072436Dent SF, Gelmon KA, Chi KN, Jonker DJ, Wainman N, Capier CA, Chen EX, Lyons JF, Seymour L. NCIC CTG IND.181: phase I study of AT9283 given as a weekly 24 hour infusion in advanced malignancies. Invest New Drugs. 2013 Dec;31(6):1522-9. doi: 10.1007/s10637-013-0018-9. Epub 2013 Sep 27.
- Individual participant dataSharing planned: No
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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.
Karen A. Gelmon, MD study chair
British Columbia Cancer Agency
Susan F. Dent, MD study chair
Ottawa Regional Cancer Centre
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 Aurora kinase inhibitor AT9283 in people with Non-Hodgkins Lymphoma and Unspecified Adult Solid Tumor, Protocol Specific, run by NCIC Clinical Trials Group at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 4 Aug 2023. 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 Canada. 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 of Aurora kinase inhibitor AT9283 (AT9283) (time frame: 1 year). The study lists 4 primary outcomes in all. 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 NCT00443976, 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 4 Aug 2023.