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MLN0128 in Recurrent/Metastatic Merkel Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02514824
Recruitment Status : Active, not recruiting
First Posted : August 4, 2015
Last Update Posted : February 8, 2019
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Robert I. Haddad, MD, Dana-Farber Cancer Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Merkel Cell Carcinoma Drug: MLN0128 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MLN0128 in Recurrent/Metastatic Merkel Cell Carcinoma
Actual Study Start Date : September 22, 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020

Arm Intervention/treatment
Experimental: MLN0128
  • Dose escalation will occur using a standard 3+3 dose escalation approach. Each cohort should be evaluated for tolerability after completing 2 cycles of treatment before proceeding to escalation or de-escalation. The phase II part of the study will use the phase II dose or RP2D determined during the phase I part of the study.
  • MLN0128, orally, on predetermined days per treatment cycle
Drug: MLN0128
Investigational mTOR kinase inhibitor
Other Name: INK128

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 56 days ]
    Based on MTD in phase I, the recommended dose for phase II (RP2D) will be determined

  2. Overall Response Rate (ORR) [ Time Frame: From registration to up to 2 years ]

Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From registration to up to 2 years ]
  2. Progression-free survival (PFS) [ Time Frame: From registration to up to 2 years ]
  3. Adverse Events (AEs) [ Time Frame: 30 days before registration to 30 days after the last dose ]
  4. Response Biomarkers including p4EBP1, PSK6, pCAD and Merkel cell polyomavirus (MCV) Large T antigen (LT) and small T antigen (ST) [ Time Frame: From registration to up to 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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:

    • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02514824

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United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Millennium Pharmaceuticals, Inc.
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Principal Investigator: Robert Haddad, MD Dana-Farber Cancer Institute
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Responsible Party: Robert I. Haddad, MD, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT02514824    
Other Study ID Numbers: 15-223
First Posted: August 4, 2015    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data (IPD) will not be shared. Cumulative data will be posted here and published.
Keywords provided by Robert I. Haddad, MD, Dana-Farber Cancer Institute:
recurrent merkel cell carcinoma
metastatic merkel cell carcinoma
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue