Trial Outcomes & Findings for A Study of Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-056) (NCT NCT01431534)

Last Updated: 2019-03-01

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

Cycle 1 (cycle = 28 days)

Results posted on

2019-03-01

Participant Flow

Participant milestones

Participant milestones
Measure	Ridaforolimus 22 mg/m^2 Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 28 mg/m^2 Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 33 mg/m^2 Participants received 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 could receive additional treatment in an extension phase of the study.
Treatment Phase STARTED	4	3	13
Treatment Phase COMPLETED	0	0	2
Treatment Phase NOT COMPLETED	4	3	11
Extension Phase STARTED	0	0	2
Extension Phase COMPLETED	0	0	2
Extension Phase NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ridaforolimus 22 mg/m^2 Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 28 mg/m^2 Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 33 mg/m^2 Participants received 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 could receive additional treatment in an extension phase of the study.
Treatment Phase Adverse Event	0	0	1
Treatment Phase Progressive Disease	4	3	10

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ridaforolimus 22 mg/m^2 n=4 Participants Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 28 mg/m^2 n=3 Participants Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 33 mg/m^2 n=13 Participants Participants received 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 could receive additional treatment in an extension phase of the study.	Total n=20 Participants Total of all reporting groups
Age, Continuous	13.0 Years STANDARD_DEVIATION 5.7 • n=93 Participants	14.7 Years STANDARD_DEVIATION 2.5 • n=4 Participants	12.2 Years STANDARD_DEVIATION 3.3 • n=27 Participants	12.8 Years STANDARD_DEVIATION 3.2 • n=483 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	1 Participants n=4 Participants	8 Participants n=27 Participants	12 Participants n=483 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants	8 Participants n=483 Participants

PRIMARY outcome

Timeframe: Cycle 1 (cycle = 28 days)

Population: 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.

Outcome measures

Outcome measures
Measure	Ridaforolimus 22 mg/m^2 n=4 Participants Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 28 mg/m^2 n=3 Participants Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 33 mg/m^2 n=13 Participants Participants received 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 could receive additional treatment in an extension phase of the study.
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)	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 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

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

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.

Outcome measures

Outcome measures
Measure	Ridaforolimus 22 mg/m^2 n=4 Participants Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 28 mg/m^2 n=3 Participants Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 33 mg/m^2 n=11 Participants Participants received 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 could receive additional treatment in an extension phase of the study.
Area Under the Concentration-Time Curve of Ridaforolimus From Time 0 to 24 Hours (AUC0-24 hr)	1340 hr*ng/mL Geometric Coefficient of Variation 31.7	2330 hr*ng/mL Geometric Coefficient of Variation 36.2	2280 hr*ng/mL Geometric Coefficient of Variation 29.8

Adverse Events

Ridaforolimus 22 mg/m^2

Serious events: 3 serious events

Other events: 4 other events

Deaths: 1 deaths

Ridaforolimus 28 mg/m^2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Ridaforolimus 33 mg/m^2

Serious events: 7 serious events

Other events: 13 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ridaforolimus 22 mg/m^2 n=4 participants at risk Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 28 mg/m^2 n=3 participants at risk Participants received 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 could receive additional treatment in an extension phase of the study.	Ridaforolimus 33 mg/m^2 n=13 participants at risk Participants received 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 could receive additional treatment in an extension phase of the study.
Gastrointestinal disorders Gastric perforation	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Gastrointestinal disorders Proctalgia	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Gastrointestinal disorders Vomiting	25.0% 1/4 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/13 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Infections and infestations Device related sepsis	25.0% 1/4 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/13 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Infections and infestations Herpes virus infection	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Infections and infestations Lung infection	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Infections and infestations Oral herpes	25.0% 1/4 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/13 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Infections and infestations Pneumonia	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Infections and infestations Rhinovirus infection	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Infections and infestations Tracheitis	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Infections and infestations Viral infection	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	25.0% 1/4 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	33.3% 1/3 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/13 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Nervous system disorders Convulsion	25.0% 1/4 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Nervous system disorders Headache	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	33.3% 1/3 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/13 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Nervous system disorders Neurological symptom	25.0% 1/4 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/13 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Nervous system disorders Partial seizures	25.0% 1/4 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/13 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 1 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/4 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	0.00% 0/3 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.	7.7% 1/13 • Number of events 2 • Up to the 17-Dec-2013 database lock (up to ~56 weeks) All participants who received at least one dose of study treatment on the base study. Per protocol, safety data from the extension period were not included in the study database and did not contribute to the primary safety analysis.