Metastatic Solid TumorsPhase 1NCT00878423
Study to Assess the Safety of Escalating Doses of AT13387 in Patients With Metastatic Solid Tumors
A Phase 1 study testing AT13387 in people with Metastatic Solid Tumors, run by Astex Pharmaceuticals, Inc. at 4 sites in United States.
Trial summary
AT13387/0001 is a dose-finding study of an experimental anticancer agent. In accordance with the protocol increasing doses of AT13387 are given to patients with advanced cancer who do not have alternative treatment options. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Solid Tumors
- What is being tested?
- AT13387
- Type of treatment
- Injection or infusion
- How many people
- 62 participants
- Where
- 4 sitesUnited States
- Study dates
- May 2008to Mar 2014
- 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
- Provision of signed informed consent.
- Age 18 years or older.
- Histological or cytological evidence of a metastatic solid tumor including lymphoma, which is refractory to standard therapy. The following tumor types are of particular interest as they may be more likely to respond to HSP90 inhibition and all efforts should be made to recruit patients into the study with these diagnoses. Only patients with these diagnoses and others thought to be responsive to HSP90 inhibitors are to be enrolled following the identification of MTD.
- Metastatic breast cancer which is HER2 positive either by FISH or 3+ immunohistochemistry staining,
- Adenocarcinoma of the prostate which is refractory to treatment with androgen depletion,
- Metastatic melanoma,
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- Stage IIIb or IV NSCLC,
- SCLC,
- High grade gliomas (patients must have been on a stable dose of corticosteroids for at least one week prior to treatment with AT13387 and have not experienced neurological deterioration during this period),
- GIST.
- ECOG performance status ≤ 2.
- Adequate marrow function as defined by:
- Hemoglobin > 9 g/dL,
- Neutrophils > 1.4 x 10^9/L,
- Platelets ≥ 100 x 10^9/L.
- Negative serum or urine pregnancy test or evidence of surgical sterility or evidence of post-menopausal status. Post-menopausal status is defined as any of the following: natural menopause with menses >1 year ago; radiation induced oophorectomy with last menses >1 year ago; chemotherapy-induced menopause with 1 year interval since last menses.
Who cannot join
- Be pregnant or lactating (women of childbearing potential must have a negative pregnancy test within 7 days prior to enrolment). Male and female patients of childbearing potential must use appropriate birth control (barrier methods, oral contraceptives and/or intrauterine devices) during the entire duration of the study, or the patient must be surgically sterile (with documentation in the patient's medical records).
- Ongoing central nervous system metastases in patients with an extracranial primary tumor (unless the patient's neurological signs or symptoms have been stable during the preceding three months and the patient has not received corticosteroid treatment for four weeks prior to study entry).
- Inadequate liver function as demonstrated by serum bilirubin > 2.5 times the upper limits of reference range (ULRR) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) ≥ 2.5 times the ULRR (unless due to the presence of liver metastases when ALT and/or AST may be up to five times the upper limits of reference range). Patients with an isolated increase in ALP ≤ 5 times ULRR in the absence of liver metastases but with known bone metastases are eligible for the study.
- Left ventricular ejection fraction <50% on echocardiography or MUGA scan.
- Moderate or severe renal impairment defined as serum creatinine > 1.5 ULRR or > + proteinuria on two occasions no less than 24 hours apart.
- Previous treatment with a HSP90 inhibitor.
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- Anticancer therapies that have not been completed at least 28 days prior to treatment with AT13387 (other than surgery or treatment with a protein kinase inhibitor which must have been completed no less than one week prior to treatment with AT13387).
- Incomplete recovery from previous radiotherapy or surgery other than residual cutaneous effects or stable < Grade 2 gastrointestinal toxicity.
- History of an ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months of study entry.
- QTc > 460 ms according to the Fridericia's correction.
- Previous malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumor was treated with curative intent more than 2 years prior to study entry.
- Any evidence of severe or uncontrolled systemic conditions (e.g., systemic infection) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
- Prior history of infection with human immunodeficiency virus (HIV), known active hepatitis B or C viruses - screening for viral infections is not required for entry to this study.
- Chronic treatment with known CYP450 inducers e.g. phenytoin, within four weeks of receiving treatment with AT13387 (see Appendix D for list) other than Dexamethasone in patients with glioma.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114-2696
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
The University of Arizona Cancer Center
Tucson, Arizona, 85724-5024
About this study
Official title: A Phase I Open-label Dose Escalation Study of AT13387 in Patients With Metastatic Solid Tumors
AT13387/0001 is a dose-finding study of an experimental anticancer agent. In accordance with the protocol increasing doses of AT13387 are given to patients with advanced cancer who do not have alternative treatment options. The preferred dose of AT13387 will be identified according to the side effects experienced at different dose levels.
Read the detailed description
Increasing doses of AT13387 will be administered to groups of 3 to 6 patients at each dose level. The pharmacokinetic profile of AT13387 following a one hour intravenous infusion will be determined and the effect of AT13387 on predefined biomarkers in blood plasma and circulating white blood cells will be established. Patients will be closely monitored for the development of side effects which would preclude further dose escalation.
- Conditions
- Metastatic Solid Tumors
- Being tested
- AT13387
- Keywords
- HSP90, Metastatic solid tumor including lymphoma which are, refractory to standard therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT13387Drug
Two dosing schedules will be evaluated; twice or once weekly dosing, on three weeks out of four. The starting dose for the once weekly schedule was 10mg/m2/dose, given as one hour intravenous (IV) infusions on Days 1, 4, 8, 11, 15 and 18 of a twenty-eight day cycle. The starting dose for the twice weekly schedule, given as one hour intravenous (IV) infusions on Days 1, 8 and 15 of a twenty-eight day cycle, will be 150mg/m2/dose
AT13387Drug
Intravenous infusion over one hour on days 1, 4, 8, 11, 15 and 18, every four weeks or intravenous infusion over one hour on days 1, 8 and 15, every four weeks . Treatment may be continued indefinitively in the presence of clinical benefit
What is being measured
The primary outcome is the main question the study is designed to answer.
The identification of the maximum tolerated dose for twice or once weekly dosing, on three weeks out of four
Measured: 12 months
Secondary outcomes (1)
Pharmacokinetic profile, Safety and tolerability of maximum tolerated dose, pharmacodynamic effect, identify dose limiting toxicities
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2009 (estimated)
- Study startMay 2008
- Primary completionMay 2013
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astex Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00878423
- Sponsor's protocol ID
- AT13387/0001
- Status last verified
- Aug 2024
- First submitted
- 8 Apr 2009
- Last updated
- 2 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-label Dose Escalation Study of AT13387 in Patients With Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT00878423
- Acronym / sponsor ID
- AT13387/0001
- Conditions
- Metastatic Solid Tumors
- Keywords
- HSP90, Metastatic solid tumor including lymphoma which are, refractory to standard therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Astex Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2008
- Primary completion
- May 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 9 Apr 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.
AT13387/0001 is a dose-finding study of an experimental anticancer agent. In accordance with the protocol increasing doses of AT13387 are given to patients with advanced cancer who do not have alternative treatment options. The preferred dose of AT13387 will be identified according to the side effects experienced at different dose levels.
Detailed description
Increasing doses of AT13387 will be administered to groups of 3 to 6 patients at each dose level. The pharmacokinetic profile of AT13387 following a one hour intravenous infusion will be determined and the effect of AT13387 on predefined biomarkers in blood plasma and circulating white blood cells will be established. Patients will be closely monitored for the development of side effects which would preclude further dose escalation.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Provision of signed informed consent.
- Age 18 years or older.
- Histological or cytological evidence of a metastatic solid tumor including lymphoma, which is refractory to standard therapy. The following tumor types are of particular interest as they may be more likely to respond to HSP90 inhibition and all efforts should be made to recruit patients into the study with these diagnoses. Only patients with these diagnoses and others thought to be responsive to HSP90 inhibitors are to be enrolled following the identification of MTD.
- ECOG performance status ≤ 2.
- Adequate marrow function as defined by:
Key exclusion criteria (14 listed)
- Be pregnant or lactating (women of childbearing potential must have a negative pregnancy test within 7 days prior to enrolment). Male and female patients of childbearing potential must use appropriate birth control (barrier methods, oral contraceptives and/or intrauterine devices) during the entire duration of the study, or the patient must be surgically sterile (with documentation in the patient's medical records).
- Ongoing central nervous system metastases in patients with an extracranial primary tumor (unless the patient's neurological signs or symptoms have been stable during the preceding three months and the patient has not received corticosteroid treatment for four weeks prior to study entry).
- Inadequate liver function as demonstrated by serum bilirubin > 2.5 times the upper limits of reference range (ULRR) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) ≥ 2.5 times the ULRR (unless due to the presence of liver metastases when ALT and/or AST may be up to five times the upper limits of reference range). Patients with an isolated increase in ALP ≤ 5 times ULRR in the absence of liver metastases but with known bone metastases are eligible for the study.
- Left ventricular ejection fraction <50% on echocardiography or MUGA scan.
- Moderate or severe renal impairment defined as serum creatinine > 1.5 ULRR or > + proteinuria on two occasions no less than 24 hours apart.
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 |
|---|---|---|
| AT13387Two dosing schedules will be evaluated; twice or once weekly dosing, on three weeks out of four. The starting dose for the once weekly schedule was 10mg/m2/dose, given as one hour intravenous (IV) infusions on Days 1, 4, 8, 11, 15 and 18 of a twenty-eight day cycle. The starting dose for the twice weekly schedule, given as one hour intravenous (IV) infusions on Days 1, 8 and 15 of a twenty-eight day cycle, will be 150mg/m2/dose | Drug | – |
| AT13387Intravenous infusion over one hour on days 1, 4, 8, 11, 15 and 18, every four weeks or intravenous infusion over one hour on days 1, 8 and 15, every four weeks . Treatment may be continued indefinitively in the presence of clinical benefit | Drug | – |
Primary outcome
The identification of the maximum tolerated dose for twice or once weekly dosing, on three weeks out of four
Time frame: 12 months
1 secondary outcome
Pharmacokinetic profile, Safety and tolerability of maximum tolerated dose, pharmacodynamic effect, identify dose limiting toxicities
Time frame: 12 months
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 2 Aug 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
4 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 AT13387 in people with Metastatic Solid Tumors, run by Astex Pharmaceuticals, Inc. at 4 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 16 inclusion and 14 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 2 Aug 2024. 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. 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 identification of the maximum tolerated dose for twice or once weekly dosing, on three weeks out of four (time frame: 12 months). 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 2 Aug 2024.