Advanced Cancers
Conditions
Brief summary
To describe the long-term safety of deforolimus (ridaforolimus, MK-8669) in participants for whom a clinical benefit has been established in a prior parent trial (MK-8669-013, NCT00060645; MK-8669-016, NCT00112372; and MK-8669-028, NCT00704054) with deforolimus and/or in those who remain in long-term follow-up.
Interventions
DRUGRidaforolimus Tablet
Ridaforolimus 10 mg oral tablet
DRUGRidaforolimus Intravenous (IV) Infusion
Ridaforolimus IV infusion administered once daily for 5 days every 2 weeks in a 28-day cycle (two 2-week courses equals 1 cycle).
Sponsors
Ariad Pharmaceuticals
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have participated on a deforolimus (ridaforolimus) parent trial * Must have derived a clinical benefit from the parent trial * Is not on any other anti-cancer treatment(s) unless the therapy was allowed on the parent protocol * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 if the participant is scheduled to receive treatment with deforolimus; no requirement if the participant is included for follow-up purposes only * Participant of childbearing potential must have a negative pregnancy test within 7 days prior to screening and must use approved contraceptive from screening until 30 days after the last dose of study drug * Signed informed consent
Exclusion criteria
* Has not participated on a parent trial * Women who are to receive study drug who are pregnant or lactating * Any condition in the Investigator's judgment that renders the participant unable to fully understand and provide informed consent and/or comply with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event | Up to approximately 2991 days, including 30 days after the last dose (through data cut-off date of 03 Apr 2017) | An adverse event is defined as any unintended or undesirable, noxious, or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study drug. The number of participants who experienced an adverse event is presented. |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to approximately 2961 days (through data cut-off date of 03 Apr 2017) | An adverse event is defined as any unintended or undesirable, noxious, or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study drug. The number of participants who discontinued study drug due to an adverse event is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 2991 days (through data cut-off date of 03 Apr 2017) | OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. |
| Progression-free Survival (PFS) | Up to approximately 2961 days (through data cut-off date of 03 Apr 2017) | PFS was defined as the time from randomization to the first documented progressive disease (PD), or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS for all participants is presented in days. |
| Duration of Response (DOR) | Up to approximately 2961 days (through data cut-off date of 03 Apr 2017) | For participants who demonstrated a confirmed response (Completed Response \[CR\] or Partial Response \[PR\]) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. |
Participant flow
Recruitment details
Participants who continued to receive clinical benefit from ridaforolimus, or who were being followed for long-term safety and efficacy under the following prior protocols were eligible for enrollment into this extension study: MK-8669-013, NCT00060645; MK-8669-016, NCT00112372; and MK-8669-028, NCT00704054.
Pre-assignment details
Participants may have continued ridaforolimus IV infusion at the same dose from the parent trial before being switched to ridaforolimus oral tablet.
Participants by arm
| Arm | Count |
|---|---|
| Ridaforolimus 10 mg Days 1-5 Ridaforolimus 10 mg administered orally once daily on Days 1-5 per week. | 3 |
| Ridaforolimus 10 mg Days 1-6 Ridaforolimus 10 mg administered orally once daily on Days 1-6 per week. | 1 |
| Ridaforolimus 20 mg Days 1-5 Ridaforolimus 20 mg administered once daily on Days 1-5 per week. | 1 |
| Ridaforolimus 30 mg Days 1-5 Ridaforolimus 30 mg administered orally once daily on Days 1-5 per week. | 1 |
| Ridaforolimus 40 mg Days 1-5 Ridaforolimus 40 mg administered orally once daily on Days 1-5 per week. | 1 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Progressive disease | 2 | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Ridaforolimus 10 mg Days 1-5 | Ridaforolimus 10 mg Days 1-6 | Ridaforolimus 20 mg Days 1-5 | Ridaforolimus 30 mg Days 1-5 | Ridaforolimus 40 mg Days 1-5 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 47.7 Years STANDARD_DEVIATION 15 | 47.0 Years | 67.0 Years | 53.0 Years | 13.0 Years | 46.1 Years STANDARD_DEVIATION 18.4 |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 0 / 1 | 0 / 1 | 0 / 1 | 1 / 1 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 3 / 3 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 3 | 1 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
An adverse event is defined as any unintended or undesirable, noxious, or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study drug. The number of participants who discontinued study drug due to an adverse event is presented.
Time frame: Up to approximately 2961 days (through data cut-off date of 03 Apr 2017)
Population: All participants who received any study drug on this extension protocol according to their actual treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ridaforolimus 10 mg Days 1-5 | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Ridaforolimus 10 mg Days 1-6 | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Ridaforolimus 20 mg Days 1-5 | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Ridaforolimus 30 mg Days 1-5 | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Ridaforolimus 40 mg Days 1-5 | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
Primary
Number of Participants Who Experienced an Adverse Event
An adverse event is defined as any unintended or undesirable, noxious, or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study drug. The number of participants who experienced an adverse event is presented.
Time frame: Up to approximately 2991 days, including 30 days after the last dose (through data cut-off date of 03 Apr 2017)
Population: All participants who received any study drug on this extension protocol according to their actual treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ridaforolimus 10 mg Days 1-5 | Number of Participants Who Experienced an Adverse Event | 3 Participants |
| Ridaforolimus 10 mg Days 1-6 | Number of Participants Who Experienced an Adverse Event | 1 Participants |
| Ridaforolimus 20 mg Days 1-5 | Number of Participants Who Experienced an Adverse Event | 1 Participants |
| Ridaforolimus 30 mg Days 1-5 | Number of Participants Who Experienced an Adverse Event | 1 Participants |
| Ridaforolimus 40 mg Days 1-5 | Number of Participants Who Experienced an Adverse Event | 1 Participants |
Secondary
Duration of Response (DOR)
For participants who demonstrated a confirmed response (Completed Response \[CR\] or Partial Response \[PR\]) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment.
Time frame: Up to approximately 2961 days (through data cut-off date of 03 Apr 2017)
Population: All participants who received any study drug on this extension protocol according to their actual treatment and who experienced a CR or PR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ridaforolimus 20 mg Days 1-5 | Duration of Response (DOR) | 2894 Days |
Secondary
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up.
Time frame: Up to approximately 2991 days (through data cut-off date of 03 Apr 2017)
Population: All participants who received any study drug on this extension protocol according to their actual treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ridaforolimus 10 mg Days 1-5 | Overall Survival (OS) | 1803.67 Days |
| Ridaforolimus 10 mg Days 1-6 | Overall Survival (OS) | 2933 Days |
| Ridaforolimus 20 mg Days 1-5 | Overall Survival (OS) | 2962 Days |
| Ridaforolimus 30 mg Days 1-5 | Overall Survival (OS) | 2334 Days |
| Ridaforolimus 40 mg Days 1-5 | Overall Survival (OS) | 247 Days |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from randomization to the first documented progressive disease (PD), or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS for all participants is presented in days.
Time frame: Up to approximately 2961 days (through data cut-off date of 03 Apr 2017)
Population: All participants who received any study drug on this extension protocol according to their actual treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ridaforolimus 10 mg Days 1-5 | Progression-free Survival (PFS) | 488.67 Days |
| Ridaforolimus 10 mg Days 1-6 | Progression-free Survival (PFS) | 2858 Days |
| Ridaforolimus 20 mg Days 1-5 | Progression-free Survival (PFS) | 2936 Days |
| Ridaforolimus 30 mg Days 1-5 | Progression-free Survival (PFS) | 1142 Days |
| Ridaforolimus 40 mg Days 1-5 | Progression-free Survival (PFS) | 29 Days |