Merkel Cell CarcinomaPhase 1/2NCT02514824
MLN0128 in Recurrent/Metastatic Merkel Cell Carcinoma
A Phase 1/2 study testing MLN0128 in people with Merkel Cell Carcinoma, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
This research study is studying a targeted therapy as a possible treatment for merkel cell carcinoma. The name of the study intervention involved in this study is: MLN0128. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Merkel Cell Carcinoma
- What is being tested?
- MLN0128
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to Jun 2017
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Metastatic or recurrent MCC confirmed by histology
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan (see section 10 for the evaluation of measureable disease). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented
- Age 18 years or older
- ECOG performance status ≤ 2
- Participants must have normal organ and marrow function
- Female patients who:
Show all 17Show fewer
- Are postmenopausal for at least 1 year before the screening visit
- --- OR
- Are surgically sterile --- OR
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time
- Male patients, even if surgically sterilized (ie, status post-vasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, or
- Agree to completely abstain from heterosexual intercourse
- Treatment with strong CYP2C19, CYP3A4, and CYP2C9 inhibitors and/or inducers
- Tissue for correlative studies must be available (paraffinized or frozen)
- Ability to swallow oral medications and maintain an empty stomach state for 2 hours prior to the MLN0128 dose and for 1 hour following administration
- Ability to understand and the willingness to sign a written informed consent
Who cannot join
- Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study
- The subject has active brain metastases or epidural disease
- Participants who are receiving any other investigational agents within 14 days before the first dose of study drug
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
- Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug
- Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128
Show all 23Show fewer
- Poorly controlled diabetes mellitus
- History of any of the following within the last 6 months prior to study entry:
- Ischemic myocardial event
- Ischemic cerebrovascular event
- Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia
- Placement of a pacemaker for control of rhythm
- New York Heart Association (NYHA) Class III or IV heart failure
- Pulmonary embolism
- Significant active cardiovascular or pulmonary disease at the time of study entry, including:
- Uncontrolled high blood pressure
- Pulmonary hypertension
- Uncontrolled asthma
- Significant valvular disease; severe regurgitation or stenosis
- Medically significant (symptomatic) bradycardia
- History of arrhythmia requiring an implantable cardiac defibrillator
- Baseline prolongation of the rate-corrected QT interval (QTc)
- Initiation of treatment with hematopoietic growth factors, transfusions of blood and blood products, or systemic corticosteroids
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
This research study is studying a targeted therapy as a possible treatment for merkel cell carcinoma.
- The name of the study intervention involved in this study is: MLN0128.
Read the detailed description
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.
- Conditions
- Merkel Cell Carcinoma
- Being tested
- MLN0128
- Keywords
- recurrent merkel cell carcinoma, metastatic merkel cell carcinoma
- Medical subject headings
- Carcinoma, Merkel Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN0128Drug
Also called INK128
Investigational mTOR kinase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1: MLN01283 3 mg (Phase 1) | Experimental | 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. Receives: Drug: MLN0128 |
| Dose Level 2: MLN01283 4 mg (Phase 1) | Experimental | 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. Receives: Drug: MLN0128 |
| Dose Level 3: MLN01283 5 mg (Phase 1) | Experimental | 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. Receives: Drug: MLN0128 |
| MLN01283 RP2D (Phase 2) | Experimental | 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. Receives: Drug: MLN0128 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: The observation period for DLT evaluation was the first 28 days (cycle 1) of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2015 (estimated)
- Study startOct 2015
- Primary completionApr 2017
- Study completionJun 2017
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.
- Other trials for Merkel Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Robert I. Haddad, MD, Dana-Farber Cancer Institute
- Investigators
- Robert Haddad, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02514824
- Sponsor's protocol ID
- 15-223
- Status last verified
- Dec 2020
- First submitted
- 28 Jul 2015
- Last updated
- 29 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Individual participant data (IPD) will not be shared. Cumulative data will be posted here and published.
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MLN0128 in Recurrent/Metastatic Merkel Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02514824
- Acronym / sponsor ID
- 15-223
- Conditions
- Merkel Cell Carcinoma
- Keywords
- recurrent merkel cell carcinoma, metastatic merkel cell carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Oct 2015 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 4 Aug 2015 (estimated)
- Results
- Posted 29 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a targeted therapy as a possible treatment for merkel cell carcinoma.
- The name of the study intervention involved in this study is: MLN0128.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1: MLN01283 3 mg (Phase 1) | Experimental | Drug: MLN0128Phase 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. |
| Dose Level 2: MLN01283 4 mg (Phase 1) | Experimental | Drug: MLN0128Phase 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. |
| Dose Level 3: MLN01283 5 mg (Phase 1) | Experimental | Drug: MLN0128Phase 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. |
| MLN01283 RP2D (Phase 2) | Experimental | Drug: MLN0128Phase 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Metastatic or recurrent MCC confirmed by histology
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan (see section 10 for the evaluation of measureable disease). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented
- Age 18 years or older
- ECOG performance status ≤ 2
- Participants must have normal organ and marrow function
Key exclusion criteria (23 listed)
- Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study
- The subject has active brain metastases or epidural disease
- Participants who are receiving any other investigational agents within 14 days before the first dose of study drug
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
- Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug
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 |
|---|---|---|
| MLN0128Also: INK128Investigational mTOR kinase inhibitor | Drug | 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) |
Primary outcome
MLN01283 Maximum Tolerated Dose (MTD) [Phase I]
Time frame: The observation period for DLT evaluation was the first 28 days (cycle 1) of treatment.
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).
Dose Limiting Toxicity (DLT) [Phase I]
Time frame: The observation period for DLT evaluation was the first 28 days (cycle 1) of treatment.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared. Cumulative data will be posted here and published.
Related trials for Merkel Cell Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingObservational study
Studies of Dermatologic Diseases Biospecimen Acquisition Protocol
Dermatologic Conditions, Healthy Volunteers
Not yet recruitingPhase 1/2
ASTX727 & Retifanlimab-dlwr for Advanced Merkel Cell After Progression on Anti-PD-(L)1
Merkel Cell Carcinoma, Merkel Cell Carcinoma, Stage III
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1
Evaluating BL-M14D1 in Subjects With Locally Advanced or Metastatic Small Cell Lung Cancer and Neuroendocrine Tumors
Small Cell Lung Cancer Metastatic or Locally Advanced, Neuroendocrine Cancer
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.
Robert Haddad, MD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MLN0128 in people with Merkel Cell Carcinoma, run by Dana-Farber Cancer Institute at 1 site in United States.
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 17 inclusion and 23 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 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 29 Dec 2020). 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?
MLN01283 Maximum Tolerated Dose (MTD) [Phase I] (time frame: The observation period for DLT evaluation was the first 28 days (cycle 1) of treatment.). 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?
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 29 Dec 2020.