Malignant GliomaPhase 1NCT00087451
Safety Study of AP23573 in Patients With Progressive or Recurrent Glioma (8669-023)(COMPLETED)
A Phase 1 study testing AP23573 in people with Malignant Glioma and Glioblastoma, run by Merck Sharp & Dohme LLC at 4 sites in United States.
Trial summary
A Phase I, open-label, non-randomized, sequential dose escalation cohort trial of the safety, tolerability, and maximum tolerated dose (MTD) of AP23573 when administered intravenously as a 30-minute infusion, once daily for five days, repeated every two weeks, to patients with progressive or recurrent malignant glioma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma, Glioblastoma, Gliosarcoma
- What is being tested?
- AP23573
- How many people
- 11 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2004to Nov 2005
- 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
Inclusion Criteria (Patients must meet each of the following criteria to be eligible for participation in the trial):
- Male or female patients ≥ 18 years of age
- Patients must have a radiographically suspected progressive or recurrent primary malignant glioma (glioblastoma multiforme or gliosarcoma) and must have failed standard therapy. Patients may not have received any systemic therapy for the treatment of this recurrence or relapse
- Patients must be candidates for surgical resection or open biopsy of the tumor
- Patients who have had previous surgical resection(s) are eligible
- Patients must have had minimum prior therapy of radiotherapy and documented progression of disease thereafter
- Patients must have had a tissue proven malignant glioma
- A minimum interval of at least four weeks prior to the first dose of AP23573 must have elapsed for all patients enrolling after either prior surgery or completion of prior external beam radiotherapy for initial primary diagnosis
- A minimum interval of four weeks prior to the first dose of AP23573 must have elapsed since receipt of any investigational therapy or any other chemotherapy
- Patients in the EIAC cohorts must be presently receiving a stable dose of EIAC (e.g., dilantin, phenytoin, etc.) for at least two weeks prior to the first dose of AP23573
- For patients on corticosteroids, the dose must be stable for at least one week prior to the first dose of AP23573
- Patients must be neurologically stable for at least two weeks prior to the first dose of AP23573
- Patients must have an ECOG performance status of 0 or 1
- Patients must either not be of childbearing potential or have agreed to use a medically effective method of contraception
- Patients must have adequate hematologic, renal and liver function as specified in the protocol
- Patients must be able to understand and give written informed consent
Exclusion Criteria (Patients meeting any of the following criteria are ineligible for participation in the trial):
- Women who are pregnant or lactating
- Patients with known or suspected hypersensitivity to either drugs formulated with polysorbate 80 (Tween) or any other excipient contained in the study drug formulation
- Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin)
- Patients with significant cardiovascular disease, as specified in the protocol
- Patients with known HIV infection
- Patients with any active infection requiring prescribed intervention
- Patients receiving immunosuppressive agents other than prescribed corticosteroids
- Patients who have had prior therapy with rapamycin, any rapamycin analog or tacrolimus
- Patients with inadequate recovery from any prior surgical procedure or patients having undergone any major surgical procedure within two weeks prior to the first dose of AP23573
- Patients with any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug
- Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies
- Patients with another primary malignancy within the past three years (except for non-melanoma skin cancers and cervical carcinomas in situ)
- Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements
- Patients are not permitted any chemotherapeutic agents or other antineoplastic agents either during or within four weeks prior to the first dose of AP23573. Additional excluded drugs and treatments are specified in the protocol
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Center For Neuro-Oncology, Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Brain Tumor Institute, The Cleveland Clinic
Cleveland, Ohio, 44195
The Brain Tumor Center at Duke, Duke University Medical Center
Durham, North Carolina, 27710
M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase I Sequential Ascending Dose Trial of AP23573 in Patients With Progressive or Recurrent Malignant Glioma
A Phase I, open-label, non-randomized, sequential dose escalation cohort trial of the safety, tolerability, and maximum tolerated dose (MTD) of AP23573 when administered intravenously as a 30-minute infusion, once daily for five days, repeated every two weeks, to patients with progressive or recurrent malignant glioma.
Read the detailed description
The primary objective of the study is to determine the safety, tolerability, and maximum tolerated dose (MTD) of AP23573 when administered intravenously once daily for five days repeated every two weeks to patients with progressive or recurrent gliomas who have failed standard therapy and who are or are not receiving enzyme-inducing anticonvulsant (EIAC) medications.
The secondary objectives are to: characterize the pharmacokinetic profile of AP23573 when administered daily for five days repeated every two weeks at the indicated dosage levels in patients receiving and not receiving EIAC; describe the progression-free survival at six months; describe changes in proteins affected by mTOR inhibition; describe single timepoint status of proteins affected by mTOR inhibition in tumor tissue surgical specimens after AP23573 dosing; describe the status of key proteins in the mTOR signaling pathway in archival tumor samples, if available; describe health-related quality of life at the start of the trial and prior to study drug infusion and at various timepoints throughout the trial.
Protocol Outline:
This is a Phase I, open-label, non-randomized, sequential dose escalation cohort trial of the safety, tolerability, and MTD of AP23573 when administered intravenously as a 30-minute infusion, once daily for five days, repeated every two weeks, to patients with progressive or recurrent malignant glioma.
- Conditions
- Malignant Glioma, Glioblastoma, Gliosarcoma
- Being tested
- AP23573
- Keywords
- Progressive or recurrent malignant glioma
- Medical subject headings
- Glioma, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AP23573Drug
Also called deforolimus, MK-8669, ridaforolimus was also known as deforolimus until May 2009
ridaforolimus
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2004 (estimated)
- Study startJul 2004
- Primary completionNov 2005
- Study completionNov 2005
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 Malignant GliomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- 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
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ariad Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00087451
- Sponsor's protocol ID
- 8669-023
- Other IDs
- AP23573-04-103
- Status last verified
- Aug 2015
- First submitted
- 8 Jul 2004
- Last updated
- 19 Aug 2015
- Results posted
- No
Publications
Reardon DA, Wen PY, Alfred Yung WK, Berk L, Narasimhan N, Turner CD, Clackson T, Rivera VM, Vogelbaum MA. Ridaforolimus for patients with progressive or recurrent malignant glioma: a perisurgical, sequential, ascending-dose trial. Cancer Chemother Pharmacol. 2012 Apr;69(4):849-60. doi: 10.1007/s00280-011-1773-y. Epub 2011 Oct 30.
PubMed 22037923
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Sequential Ascending Dose Trial of AP23573 in Patients With Progressive or Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT00087451
- Acronym / sponsor ID
- 8669-023
- Conditions
- Malignant Glioma, Glioblastoma, Gliosarcoma
- Keywords
- Progressive or recurrent malignant glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Collaborators
- Ariad Pharmaceuticals
- Study start
- Jul 2004
- Primary completion
- Nov 2005 (actual)
- Study completion
- Nov 2005 (actual)
- First posted
- 13 Jul 2004 (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.
A Phase I, open-label, non-randomized, sequential dose escalation cohort trial of the safety, tolerability, and maximum tolerated dose (MTD) of AP23573 when administered intravenously as a 30-minute infusion, once daily for five days, repeated every two weeks, to patients with progressive or recurrent malignant glioma.
Detailed description
The primary objective of the study is to determine the safety, tolerability, and maximum tolerated dose (MTD) of AP23573 when administered intravenously once daily for five days repeated every two weeks to patients with progressive or recurrent gliomas who have failed standard therapy and who are or are not receiving enzyme-inducing anticonvulsant (EIAC) medications.
The secondary objectives are to: characterize the pharmacokinetic profile of AP23573 when administered daily for five days repeated every two weeks at the indicated dosage levels in patients receiving and not receiving EIAC; describe the progression-free survival at six months; describe changes in proteins affected by mTOR inhibition; describe single timepoint status of proteins affected by mTOR inhibition in tumor tissue surgical specimens after AP23573 dosing; describe the status of key proteins in the mTOR signaling pathway in archival tumor samples, if available; describe health-related quality of life at the start of the trial and prior to study drug infusion and at various timepoints throughout the trial.
Protocol Outline:
This is a Phase I, open-label, non-randomized, sequential dose escalation cohort trial of the safety, tolerability, and MTD of AP23573 when administered intravenously as a 30-minute infusion, once daily for five days, repeated every two weeks, to patients with progressive or recurrent malignant glioma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- 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
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 |
|---|---|---|
| AP23573Also: deforolimus, MK-8669, ridaforolimus was also known as deforolimus until May 2009ridaforolimus | Drug | – |
Primary outcome
Not reported in the source record.
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 19 Aug 2015.
- Results publication: PubMed 22037923Reardon DA, Wen PY, Alfred Yung WK, Berk L, Narasimhan N, Turner CD, Clackson T, Rivera VM, Vogelbaum MA. Ridaforolimus for patients with progressive or recurrent malignant glioma: a perisurgical, sequential, ascending-dose trial. Cancer Chemother Pharmacol. 2012 Apr;69(4):849-60. doi: 10.1007/s00280-011-1773-y. Epub 2011 Oct 30.
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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 AP23573 in people with Malignant Glioma and Glioblastoma, run by Merck Sharp & Dohme LLC 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?
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 19 Aug 2015. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00087451, 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 19 Aug 2015.