Solid TumorsPhase 1NCT00704054
A Multi-Center Phase I Study of Intravenous Deforolimus (AP23573, MK-8669) Administered QDX5 Every Other Week in Pediatric Patients With Advanced Solid Tumors (8669-028)(COMPLETED)
A Phase 1 study testing ridaforolimus in people with Solid Tumors, run by Merck Sharp & Dohme LLC.
Trial summary
Ridaforolimus (Deforolimus, AP23573, MK-8669) is an mTor inhibitor shown to have promising activity in adults with a variety of solid malignancies, particularly the sarcomas. To date, no studies to evaluate appropriate dosing or to obtain pharmacokinetic data in pediatric patients have been conducted. Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- Conditions the study is for
- Solid Tumors
- What is being tested?
- ridaforolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- Jan 2008to Jun 2010
- 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 1 year to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female age 1 to <18 years at the time of study entry for the dose escalation portion of the study
- Histologic diagnosis of a malignant lymphoma or solid tumor, including tumors of the central nervous system that has progressed in the opinion of the investigator despite standard therapy or for which no effective standard therapy is known
- Patients may have measurable or non-measurable disease as defined by RECIST
- Patients with brainstem glioma or intrinsic pontine glioma do not need biopsy proof of the diagnosis, but must have documentation at their local institution that there is agreement among the attending oncologist and/or neuro-oncologist, radiologist, and neurosurgeon/pediatric neurosurgeon that the diagnostic imaging studies are consistent with a diagnosis of brainstem or intrinsic pontine glioma
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, surgery or radiotherapy prior to entering this study
- Performance Status: EGOG 0-2 for patients age 16 and older; Karnofsky >40% for patients >10 years of age; Lansky Play Scale >40 for children < 10 years of age
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- Life expectancy greater than or equal to 12 weeks
- There is no limit to the number of prior treatment regimens provided that performance status, organ function, and life expectancy meet the study criteria
- No persistent toxicities from previous therapies > Grade 2 by NCI CTCAE version 3. For patients with CNS tumors ONLY, if baseline neurotoxicity due to primary tumor involvement or post-operative complications, Grade 3 neurotoxicity is allowed if stable
- Normal organ and marrow function
- For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment
- Patients who enter this study and their sexual partners who are of childbearing potential must agree to use an effective form of contraception
Who cannot join
- Patients who have had chemotherapy or radiotherapy within three (3) weeks (or six weeks for nitrosoureas or mitomycin C) prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients receiving any other investigational agents or using any investigational devices
- Patients with leukemia
- Patients who have previously received deforolimus or other rapamycin analogs
- History of allergic reactions (in opinion of the investigator) attributed to compounds of similar chemical or biologic composition to deforolimus and its excipients used in administration
- Uncontrolled intercurrent illness
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- Pregnant women are excluded from this study because the teratogenic or abortifacient effects of deforolimus are not known at this time
- Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, known HIV-positive patients are excluded from the study because of possible pharmacokinetic interactions with deforolimus
- Autologous or allogeneic stem cell transplant <3 months prior to enrollment; any evidence of on-going graft versus host disease (GVHD), or GVHD requiring immunosuppressive therapy. Patients who have had prior stem cell transplant regimens must be discussed with and approved by the principal investigator prior to registration
About this study
Official title: A Multi-Center Phase I Study of Intravenous Deforolimus (AP23573, MK-8669) Administered QDX5 Every Other Week in Pediatric Patients With Advanced Solid Tumors
Ridaforolimus (Deforolimus, AP23573, MK-8669) is an mTor inhibitor shown to have promising activity in adults with a variety of solid malignancies, particularly the sarcomas. To date, no studies to evaluate appropriate dosing or to obtain pharmacokinetic data in pediatric patients have been conducted. Sarcomas are the second most common solid malignancies in children and young adults, and for those patients with recurrent or refractory disease, new therapies are needed. This initial evaluation of ridaforolimus will help define appropriate dosing and toxicity evaluations, as well as establish the first pharmacokinetic and biologic correlative data in pediatric patients treated with ridaforolimus.
- Conditions
- Solid Tumors
- Being tested
- ridaforolimus
- Keywords
- Pediatric, Solid Tumor, CNS Tumor, Lymphoma
- Medical subject headings
- Central Nervous System Neoplasms, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ridaforolimusDrug
Also called AP23573, deforolimus, MK-8669
Ridaforolimus is given as an IV infusion over 30 minutes on days 1-5 and 15-19 of each 28 day cycle. For children less than 10 kg body weight, dosing will be adjusted.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Ridaforolimus is given as an IV infusion over 30 minutes on days 1-5 and 15-19 of each 28 day cycle. For children less than 10 kg body weight, dosing will be adjusted. Receives: Drug: ridaforolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish the DLT and the MTD of ridaforolimus administered daily x 5 every 14 days in pediatric patients with recurrent/refractory solid tumors, including lymphoma and tumors of the central nervous system.
Measured: Duration of trial
Secondary outcomes (3)
To determine the pharmacokinetic and pharmacodynamic properties of ridaforolimus in pediatric patients with recurrent/refractory solid tumors, including tumors of the central nervous system. Screening at Day 1-18, Cycle 2 Day 1, Cycle 2 Day 15.
Measured: Duration of trial
To evaluate the safety and efficacy data of ridaforolimus when administered at the MTD or recommended phase II dose and schedule in an expanded cohort of patients when administered daily x 5 every 14 days
Measured: Duration of trial
To assess pharmacogenomic parameters from archival tumor specimens that may correlate with response to ridaforolimus.
Measured: Duration of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2008 (estimated)
- Study startJan 2008
- Primary completionJun 2010
- Study completionJun 2010
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 Solid TumorsStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- H. Lee Moffitt Cancer Center and Research Institute, Pediatric Cancer Foundation, University of Colorado, Denver, Johns Hopkins All Children's Hospital, Memorial Sloan Kettering Cancer Center
- Responsible party
- Sponsor
- Investigators
- Lisa Gore, MD, Principal investigator, University of Colorado, DenverChristopher Turner, MD, Study director, Ariad Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00704054
- Sponsor's protocol ID
- 8669-028
- Other IDs
- SUN08-01, AP23573-07-110
- Status last verified
- Feb 2015
- First submitted
- 23 Jun 2008
- Last updated
- 13 Feb 2015
- Results posted
- No
Publications
Gore L, Trippett TM, Katzenstein HM, Boklan J, Narendran A, Smith A, Macy ME, Rolla K; Pediatric Oncology Experimental Therapeutics Investigators' Consortium (POETIC); Narashimhan N, Squillace RM, Turner CD, Haluska FG, Nieder M. A multicenter, first-in-pediatrics, phase 1, pharmacokinetic and pharmacodynamic study of ridaforolimus in patients with refractory solid tumors. Clin Cancer Res. 2013 Jul 1;19(13):3649-58. doi: 10.1158/1078-0432.CCR-12-3166. Epub 2013 May 9.
PubMed 23659969
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center Phase I Study of Intravenous Deforolimus (AP23573, MK-8669) Administered QDX5 Every Other Week in Pediatric Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00704054
- Acronym / sponsor ID
- 8669-028
- Conditions
- Solid Tumors
- Keywords
- Pediatric, Solid Tumor, CNS Tumor, Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Collaborators
- H. Lee Moffitt Cancer Center and Research Institute, Pediatric Cancer Foundation, University of Colorado, Denver, Johns Hopkins All Children's Hospital, Memorial Sloan Kettering Cancer Center
- Study start
- Jan 2008
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 24 Jun 2008 (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.
Ridaforolimus (Deforolimus, AP23573, MK-8669) is an mTor inhibitor shown to have promising activity in adults with a variety of solid malignancies, particularly the sarcomas. To date, no studies to evaluate appropriate dosing or to obtain pharmacokinetic data in pediatric patients have been conducted. Sarcomas are the second most common solid malignancies in children and young adults, and for those patients with recurrent or refractory disease, new therapies are needed. This initial evaluation of ridaforolimus will help define appropriate dosing and toxicity evaluations, as well as establish the first pharmacokinetic and biologic correlative data in pediatric patients treated with ridaforolimus.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: ridaforolimusRidaforolimus is given as an IV infusion over 30 minutes on days 1-5 and 15-19 of each 28 day cycle. For children less than 10 kg body weight, dosing will be adjusted. |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- Male or female age 1 to <18 years at the time of study entry for the dose escalation portion of the study
- Histologic diagnosis of a malignant lymphoma or solid tumor, including tumors of the central nervous system that has progressed in the opinion of the investigator despite standard therapy or for which no effective standard therapy is known
- Patients may have measurable or non-measurable disease as defined by RECIST
- Patients with brainstem glioma or intrinsic pontine glioma do not need biopsy proof of the diagnosis, but must have documentation at their local institution that there is agreement among the attending oncologist and/or neuro-oncologist, radiologist, and neurosurgeon/pediatric neurosurgeon that the diagnostic imaging studies are consistent with a diagnosis of brainstem or intrinsic pontine glioma
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, surgery or radiotherapy prior to entering this study
Key exclusion criteria (9 listed)
- Patients who have had chemotherapy or radiotherapy within three (3) weeks (or six weeks for nitrosoureas or mitomycin C) prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients receiving any other investigational agents or using any investigational devices
- Patients with leukemia
- Patients who have previously received deforolimus or other rapamycin analogs
- History of allergic reactions (in opinion of the investigator) attributed to compounds of similar chemical or biologic composition to deforolimus and its excipients used in administration
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 |
|---|---|---|
| ridaforolimusAlso: AP23573, deforolimus, MK-8669Ridaforolimus is given as an IV infusion over 30 minutes on days 1-5 and 15-19 of each 28 day cycle. For children less than 10 kg body weight, dosing will be adjusted. | Drug | 1 |
Primary outcome
To establish the DLT and the MTD of ridaforolimus administered daily x 5 every 14 days in pediatric patients with recurrent/refractory solid tumors, including lymphoma and tumors of the central nervous system.
Time frame: Duration of trial
3 secondary outcomes
To determine the pharmacokinetic and pharmacodynamic properties of ridaforolimus in pediatric patients with recurrent/refractory solid tumors, including tumors of the central nervous system. Screening at Day 1-18, Cycle 2 Day 1, Cycle 2 Day 15.
Time frame: Duration of trial
To evaluate the safety and efficacy data of ridaforolimus when administered at the MTD or recommended phase II dose and schedule in an expanded cohort of patients when administered daily x 5 every 14 days
Time frame: Duration of trial
To assess pharmacogenomic parameters from archival tumor specimens that may correlate with response to ridaforolimus.
Time frame: Duration of trial
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 13 Feb 2015.
- Results publication: PubMed 23659969Gore L, Trippett TM, Katzenstein HM, Boklan J, Narendran A, Smith A, Macy ME, Rolla K; Pediatric Oncology Experimental Therapeutics Investigators' Consortium (POETIC); Narashimhan N, Squillace RM, Turner CD, Haluska FG, Nieder M. A multicenter, first-in-pediatrics, phase 1, pharmacokinetic and pharmacodynamic study of ridaforolimus in patients with refractory solid tumors. Clin Cancer Res. 2013 Jul 1;19(13):3649-58. doi: 10.1158/1078-0432.CCR-12-3166. Epub 2013 May 9.
- Pediatric Cancer FoundationLink provided by the sponsor.
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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.
Lisa Gore, MD principal investigator
University of Colorado, Denver
Christopher Turner, MD study director
Ariad Pharmaceuticals
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ridaforolimus in people with Solid Tumors, run by Merck Sharp & Dohme LLC.
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 12 inclusion and 9 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 13 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
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?
To establish the DLT and the MTD of ridaforolimus administered daily x 5 every 14 days in pediatric patients with recurrent/refractory solid tumors, including lymphoma and tumors of the central nervous system. (time frame: Duration of trial). 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 NCT00704054, 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 13 Feb 2015.