Solid TumorsPhase 1NCT01431534

A Study of Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-056)

A Phase 1 study testing Ridaforolimus in people with Solid Tumors, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 6 to 17 years
Conditions the study is for: Solid Tumors
What is being tested?: Ridaforolimus
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: No sites listed yet
Study dates: 30 Jan 2012to 25 May 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 6 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Histologic or cytologic diagnosis of a malignant solid tumor, including tumors of the central nervous system and lymphoma, that have progressed despite standard therapy or for which no effective standard therapy is known. Participants who have received standard therapy and continue to have biopsy-proven residual stable disease are eligible
Measurable or non-measurable disease
Must be able to swallow tablets
Performance Status: Lansky Play Scale ≥70 for children <10 years of age; Karnofsky score ≥70 for children ≥10 to <16 years; or Eastern Cooperative Oncology Group (ECOG) Status 0-2 for patients age 16 and older
Adequate organ function
For females of reproductive potential, a negative pregnancy test must be documented within 72 hours of receiving the first dose of study medication
Participants of reproductive potential must agree to use (or have their partner use) adequate contraception throughout the study, starting with Visit 1 through 30 days after the last dose of study drug

Who cannot join

Currently receiving any other investigational agents or using any investigational devices
Leukemia
Participant previously received ridaforolimus, rapamycin, or other rapamycin analogs
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ridaforolimus
Persistent acute toxicity from previous therapy ≥Grade 2 (excluding alopecia, neuropathy, or hearing loss)
Uncontrolled intercurrent illness despite adequate therapy

Show all 9Show fewer

Pregnant or breastfeeding
Requirement for concurrent treatment with medications that are inducers or inhibitors of cytochrome P450 (CYP3A)
Poorly controlled Type 1 or 2 diabetes

About this study

Official title: A Phase I Study of Ridaforolimus in Pediatric Patients With Advanced Solid Tumors

The main objectives of this trial are to determine the recommended dose of ridaforolimus for pediatric participants with advanced solid tumors by measuring the number of participants experiencing dose-limiting toxicities (DLTs) while on different doses of ridaforolimus, and to characterize the pharmacokinetics of ridaforolimus in these participants. The primary hypotheses of this study are that 1) the DLTs observed will be dose-dependent and allow for definition of a maximum tolerated dose (MTD) and 2) at a safe and well tolerated dose, ridaforolimus geometric mean (GM) Day-5 blood area under the concentration-time curve at 24 hours (AUC0-24) exceeds 75% (or 1304-ng*hr/mL) of the estimated GM Day-5, 40-mg AUC0-24 in adults.

Study-related visits concluded in August 2013. Participants who did not have disease progression, adequately tolerated therapy, and continued to meet eligibility criteria for 6 months after the enrollment period had been completed could continue treatment in an extension phase until they met discontinuation criteria or voluntarily withdrew.

Conditions: Solid Tumors
Being tested: Ridaforolimus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RidaforolimusDrug
Also called MK-8669
Oral administration of 10 mg enteric-coated tablets at doses of 22 mg/m^2, 28 mg/m^2, or 33 mg/m^2 based on body surface area (BSA), once daily for 5 consecutive days each week in consecutive 28-day cycles.

Study groups in NCT01431534
Study group	Role	What they receive
Ridaforolimus 22 mg/m^2	Experimental	Participants receive 22 mg/m^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months. Eligible participants can receive additional treatment in an extension phase of the study. Receives: Drug: Ridaforolimus
Ridaforolimus 28 mg/m^2	Experimental	Participants receive 28 mg/m^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months. Eligible participants can receive additional treatment in an extension phase of the study. Receives: Drug: Ridaforolimus
Ridaforolimus 33 mg/m^2	Experimental	Participants receive 33 mg/m^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months. Eligible participants can receive additional treatment in an extension phase of the study. Receives: Drug: Ridaforolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Experiencing a Dose Limiting Toxicity (DLT) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)
DLT defined using NCI-CTCAE v.4.0 as any of the following events occurring during the first 28-day cycle that were possibly, probably, or definitely study drug-related: Grade 4 neutropenia for ≥5 days; Grade 3-4 neutropenia associated with fever, antibiotics, or hospitalization for infection; Grade 4 thrombocytopenia for ≥5 days or requiring platelet transfusion; ≥Grade 3 hyperglycemia for ≥5 days despite management; ≥Grade 3 diarrhea for >24 hours despite management; ≥Grade 3 nausea or vomiting despite management; any other Grade ≥3 non-hematological toxicity persisting despite management (except alopecia, transient electrolyte abnormalities, transient Grade 3 liver function test elevations, and Grade 3 neurotoxicity for participants with baseline Grade 3 neurotoxicity); inability to complete DLT assessment period, interruption in dosing for >10 dosing days during DLT assessment period, or any delay in the initiation of the next cycle for >10 dosing days due to any related toxicity.
Measured: Cycle 1 (cycle = 28 days)
Area Under the Concentration-Time Curve of Ridaforolimus From Time 0 to 24 Hours (AUC0-24 hr)
AUC is a measure of the amount of drug in the blood over time. Whole blood samples were collected pre-dose (within 5 minutes of ridaforolimus administration) and post-dose at specified time points on Day 5 of the first week of Cycle 1 to determine AUC0-24 hr.
Measured: Day 5 of Cycle 1 [28-day cycle]: pre-dose (0.0 hours) and 0.5, 1.0, 2.0, 4.0, 8.0, and 24.0 hours after administration of ridaforolimus

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jan 201225 May 2018

First posted9 Sep 2011 (estimated)
Study start30 Jan 2012
Primary completion20 Aug 2013
Study completion25 May 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01431534
Sponsor's protocol ID: 8669-056
Other IDs: 2011-000729-55, MK-8669-056
Status last verified: Feb 2019
First submitted: 7 Sep 2011
Last updated: 1 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Pearson AD, Federico SM, Aerts I, Hargrave DR, DuBois SG, Iannone R, Geschwindt RD, Wang R, Haluska FG, Trippett TM, Geoerger B. A phase 1 study of oral ridaforolimus in pediatric patients with advanced solid tumors. Oncotarget. 2016 Dec 20;7(51):84736-84747. doi: 10.18632/oncotarget.12450.
PubMed 27713169

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

All Solid Tumors trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Study of Ridaforolimus in Pediatric Patients With Advanced Solid Tumors
ClinicalTrials.gov ID: NCT01431534
Acronym / sponsor ID: 8669-056
Conditions: Solid Tumors
Phase: Phase 1
Study type: Interventional
Recruitment status: Terminated
Enrolment: 20 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 30 Jan 2012 (actual)
Primary completion: 20 Aug 2013 (actual)
Study completion: 25 May 2018 (actual)
First posted: 9 Sep 2011 (estimated)
Results: Posted 1 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Ridaforolimus 22 mg/m^2	Experimental	Drug: RidaforolimusParticipants receive 22 mg/m^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months. Eligible participants can receive additional treatment in an extension phase of the study.
Ridaforolimus 28 mg/m^2	Experimental	Drug: RidaforolimusParticipants receive 28 mg/m^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months. Eligible participants can receive additional treatment in an extension phase of the study.
Ridaforolimus 33 mg/m^2	Experimental	Drug: RidaforolimusParticipants receive 33 mg/m^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months. Eligible participants can receive additional treatment in an extension phase of the study.

Who may qualify

Ages: 6 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (7 listed)

Histologic or cytologic diagnosis of a malignant solid tumor, including tumors of the central nervous system and lymphoma, that have progressed despite standard therapy or for which no effective standard therapy is known. Participants who have received standard therapy and continue to have biopsy-proven residual stable disease are eligible
Measurable or non-measurable disease
Must be able to swallow tablets
Performance Status: Lansky Play Scale ≥70 for children <10 years of age; Karnofsky score ≥70 for children ≥10 to <16 years; or Eastern Cooperative Oncology Group (ECOG) Status 0-2 for patients age 16 and older
Adequate organ function

Key exclusion criteria (9 listed)

Currently receiving any other investigational agents or using any investigational devices
Leukemia
Participant previously received ridaforolimus, rapamycin, or other rapamycin analogs
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ridaforolimus
Persistent acute toxicity from previous therapy ≥Grade 2 (excluding alopecia, neuropathy, or hearing loss)

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: MK-8669Oral administration of 10 mg enteric-coated tablets at doses of 22 mg/m^2, 28 mg/m^2, or 33 mg/m^2 based on body surface area (BSA), once daily for 5 consecutive days each week in consecutive 28-day cycles.	Drug	Ridaforolimus 22 mg/m^2, Ridaforolimus 28 mg/m^2, Ridaforolimus 33 mg/m^2

Primary outcome

Number of Participants Experiencing a Dose Limiting Toxicity (DLT) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)
Time frame: Cycle 1 (cycle = 28 days)
DLT defined using NCI-CTCAE v.4.0 as any of the following events occurring during the first 28-day cycle that were possibly, probably, or definitely study drug-related: Grade 4 neutropenia for ≥5 days; Grade 3-4 neutropenia associated with fever, antibiotics, or hospitalization for infection; Grade 4 thrombocytopenia for ≥5 days or requiring platelet transfusion; ≥Grade 3 hyperglycemia for ≥5 days despite management; ≥Grade 3 diarrhea for >24 hours despite management; ≥Grade 3 nausea or vomiting despite management; any other Grade ≥3 non-hematological toxicity persisting despite management (except alopecia, transient electrolyte abnormalities, transient Grade 3 liver function test elevations, and Grade 3 neurotoxicity for participants with baseline Grade 3 neurotoxicity); inability to complete DLT assessment period, interruption in dosing for >10 dosing days during DLT assessment period, or any delay in the initiation of the next cycle for >10 dosing days due to any related toxicity.
Area Under the Concentration-Time Curve of Ridaforolimus From Time 0 to 24 Hours (AUC0-24 hr)
Time frame: Day 5 of Cycle 1 [28-day cycle]: pre-dose (0.0 hours) and 0.5, 1.0, 2.0, 4.0, 8.0, and 24.0 hours after administration of ridaforolimus
AUC is a measure of the amount of drug in the blood over time. Whole blood samples were collected pre-dose (within 5 minutes of ridaforolimus administration) and post-dose at specified time points on Day 5 of the first week of Cycle 1 to determine AUC0-24 hr.

Results and safety

Results posted to the registry on 1 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ridaforolimus 22 mg/m^2	4	0
Ridaforolimus 28 mg/m^2	3	0
Ridaforolimus 33 mg/m^2	13	2

Primary outcome: Number of Participants Experiencing a Dose Limiting Toxicity (DLT) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)

Time frame: Cycle 1 (cycle = 28 days). Count of participants. Unit: Participants

Measure	Ridaforolimus 22 mg/m^2 n = 4	Ridaforolimus 28 mg/m^2 n = 3	Ridaforolimus 33 mg/m^2 n = 13
Value	0	0	1

Population analysed: Participants who completed the first 28-day cycle of therapy with adequate drug exposure (\>75% of planned study drug doses, exclusive of doses missed due to related toxicity), or who discontinued from the study due to a related DLT, were evaluable for DLT.

Primary outcome: Area Under the Concentration-Time Curve of Ridaforolimus From Time 0 to 24 Hours (AUC0-24 hr)

Time frame: Day 5 of Cycle 1 [28-day cycle]: pre-dose (0.0 hours) and 0.5, 1.0, 2.0, 4.0, 8.0, and 24.0 hours after administration of ridaforolimus. Geometric mean (Geometric Coefficient of Variation). Unit: hr*ng/mL

Measure	Ridaforolimus 22 mg/m^2 n = 4	Ridaforolimus 28 mg/m^2 n = 3	Ridaforolimus 33 mg/m^2 n = 11
Value	1340 (31.7)	2330 (36.2)	2280 (29.8)

Population analysed: Participants who received all 5 ridaforolimus doses in the first week of 28-day Cycle 1 were analyzed.

Adverse events

Time frame: Up to the 17-Dec-2013 database lock (up to ~56 weeks). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ridaforolimus 22 mg/m^2	3 of 4 (75%)	4 of 4 (100%)	1 of 4
Ridaforolimus 28 mg/m^2	2 of 3 (66.7%)	3 of 3 (100%)	1 of 3
Ridaforolimus 33 mg/m^2	7 of 13 (53.8%)	13 of 13 (100%)	1 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27713169Pearson AD, Federico SM, Aerts I, Hargrave DR, DuBois SG, Iannone R, Geschwindt RD, Wang R, Haluska FG, Trippett TM, Geoerger B. A phase 1 study of oral ridaforolimus in pediatric patients with advanced solid tumors. Oncotarget. 2016 Dec 20;7(51):84736-84747. doi: 10.18632/oncotarget.12450.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Solid Tumors

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

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.

Medical Director study director

Merck Sharp & Dohme LLC

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 7 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: stopped early, as of the sponsor's last update on 1 Mar 2019. 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?

Yes. Results are posted in the registry (first posted 1 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants Experiencing a Dose Limiting Toxicity (DLT) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) (time frame: Cycle 1 (cycle = 28 days)). 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?

On the ClinicalTrials.gov record for NCT01431534, 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 1 Mar 2019.