A Phase 1/2 interventional study of MLN0128 in Merkel Cell Carcinoma, sponsored by Dana-Farber Cancer Institute. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-12-29.
Sponsored by Dana-Farber Cancer Institute · Phase 1/2, Interventional, and Treatment
This research study is studying a targeted therapy as a possible treatment for merkel cell carcinoma.
This is a phase I/II clinical trial. A phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved MLN0128 as a treatment for any disease.
MLN0128 may prevent tumor cells from dividing and growing by selectively and potently inhibiting a chemical, mTOR kinase, which regulates cell growth and survival.
Patients with merkel cell carcinoma have been observed to sometimes carry genetic alterations in their tumor cells which may make the cancer more sensitive to inhibition by MLN0128. In this research study,the investigators are studying the usefulness of MLN0128 in merkel cell carcinoma cases.
135 studies on the registry are indexed under Carcinoma, Merkel Cell; 37 are open to participants now.
This study's enrollment of 9 is below the median of 40 across 118 interventional studies indexed under Carcinoma, Merkel Cell.
Browse Carcinoma, Merkel Cell studies →Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.
Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.
Counted across the registry records on this site, refreshed daily.
Female patients who:
Are postmenopausal for at least 1 year before the screening visit
--- OR
Male patients, even if surgically sterilized (ie, status post-vasectomy), who:
Exclusion Criteria:
History of any of the following within the last 6 months prior to study entry:
Significant active cardiovascular or pulmonary disease at the time of study entry, including:
Phase 1 dose level 1 participants receive MLN01283 3 mg orally once daily of a 28 day cycle. Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons.
Drug: MLN0128
Phase 1 dose level 2 participants receive MLN01283 4 mg orally once daily of a 28 day cycle. Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons.
Drug: MLN0128
Phase 1 dose level 3 participants receive MLN01283 5 mg orally once daily of a 28 day cycle. Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons.
Drug: MLN0128
Phase 2 participants receive MLN01283 at the recommended phase 2 dose (RP2D) orally once daily of a 28 day cycle. Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons.
Drug: MLN0128
Investigational mTOR kinase inhibitor
Also known as: INK128
MLN01283 Maximum Tolerated Dose (MTD) [Phase I]
The MLN01283 MTD is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached but the highest dose received may be the Recommended Phase II Dose (RP2D).
Time frame: The observation period for DLT evaluation was the first 28 days (cycle 1) of treatment.
Dose Limiting Toxicity (DLT) [Phase I]
A DLT was defined as an adverse event (AE) assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications meets any of the following criteria including but not limited to: grade (G) 4-5 AEs, G3 thrombocytopenia, neutropenia, AST, ALT, serum creatinine or total bilirubin 2 to 3 x upper limit normal (ULN), aymptomatic amylase and/or lipase lasting \>7 consecutive days; febrile neutropenia; G3 cardiac, hyperglycemia, mood alteration; G2 pancreatitis; G2 hyperglycemia unresolved within 14 days; G2 mood alteration unresolved in 14 days despite medical treatment; Dose interruption \>21 days due to G2 dematologic; one grade level increase neurotoxicity.
Time frame: The observation period for DLT evaluation was the first 28 days (cycle 1) of treatment.
Participants enrolled from October 2015 through March 2017.
| Milestone | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) | Dose Level 3: MLN01283 5 mg (Phase 1) | MLN01283 RP2D (Phase 2) |
|---|---|---|---|---|
| Started | 4 | 5 | 0 | 0 |
| Evaluable for dose-limiting toxicity | 3 | 5 | 0 | 0 |
| Completed | 3 | 4 | 0 | 0 |
| Not completed | 1 | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 | 0 |
| Withdrew: Dose-limiting toxicity | 0 | 1 | 0 | 0 |
The MLN01283 MTD is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached but the highest dose received may be the Recommended Phase II Dose (RP2D).
| mg | All Phase 1 Participants |
|---|---|
| MLN01283 Maximum Tolerated Dose (MTD) [Phase I] | 3 |
A DLT was defined as an adverse event (AE) assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications meets any of the following criteria including but not limited to: grade (G) 4-5 AEs, G3 thrombocytopenia, neutropenia, AST, ALT, serum creatinine or total bilirubin 2 to 3 x upper limit normal (ULN), aymptomatic amylase and/or lipase lasting \>7 consecutive days; febrile neutropenia; G3 cardiac, hyperglycemia, mood alteration; G2 pancreatitis; G2 hyperglycemia unresolved within 14 days; G2 mood alteration unresolved in 14 days despite medical treatment; Dose interruption \>21 days due to G2 dematologic; one grade level increase neurotoxicity.
| Participants | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) |
|---|---|---|
| Dose Limiting Toxicity (DLT) [Phase I] | 0 | 2 |
Objective response is defined as achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. For target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
| Participants | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) |
|---|---|---|
| Number of Participants With Objective Response (OR) [Phase 1] | 0 | 0 |
Collected over Assessed on treatment and for this study cohort the longest treatment duration was approximately 4 months in each dose level 1 and 2.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dose Level 1: MLN01283 3 mg (Phase 1) | 3/4 (75%) | 0/4 (0%) | 4/4 (100%) |
| Dose Level 2: MLN01283 4 mg (Phase 1) | 3/5 (60%) | 3/5 (60%) | 5/5 (100%) |
| Event | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) |
|---|---|---|
| NauseaGastrointestinal disorders | 0/4 | 1/5 |
| HyperglycemiaMetabolism and nutrition disorders | 0/4 | 1/5 |
| Gastrointestinal disorders - OtherGastrointestinal disorders | 0/4 | 1/5 |
| AnemiaBlood and lymphatic system disorders | 0/4 | 1/5 |
| Event | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) |
|---|---|---|
| NauseaGastrointestinal disorders | 2/4 | 4/5 |
| FatigueGeneral disorders | 3/4 | 2/5 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/4 | 3/5 |
| HyperglycemiaMetabolism and nutrition disorders | 2/4 | 3/5 |
| Weight lossInvestigations | 1/4 | 3/5 |
| PruritusSkin and subcutaneous tissue disorders | 2/4 | 1/5 |
| AnorexiaMetabolism and nutrition disorders | 1/4 | 2/5 |
| ConstipationGastrointestinal disorders | 0/4 | 2/5 |
| DiarrheaGastrointestinal disorders | 1/4 | 2/5 |
| DizzinessNervous system disorders | 0/4 | 2/5 |
The analysis population is comprised of all enrolled participants.
| Age, Continuous(years) | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) | Total |
|---|---|---|---|
| Median | 69 (52 to 74) | 69 (60 to 75) | 69 (52 to 75) |
| Sex: Female, Male(Participants) | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) | Total |
|---|---|---|---|
| Female | 4 | 5 | 9 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 4 | 5 | 9 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 4 | 5 | 9 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Dose Level 1: MLN01283 3 mg (Phase 1) | Dose Level 2: MLN01283 4 mg (Phase 1) | Total |
|---|---|---|---|
| United States | 4 | 5 | 9 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No — Individual participant data (IPD) will not be shared. Cumulative data will be posted here and published.
This study is completed, as verified in Dec 2020. You cannot join it, but the record below documents what was studied.
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Dana-Farber Cancer Institute