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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.
 
ClinicalTrials.gov Identifier: NCT02514824
Recruitment Status : Completed
First Posted : August 4, 2015
Results First Posted : December 29, 2020
Last Update Posted : December 29, 2020
Sponsor:
Collaborator:
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: Non-Randomized
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 : October 2015
Actual Primary Completion Date : April 2017
Actual Study Completion Date : June 2017


Arm Intervention/treatment
Experimental: Dose Level 1: MLN01283 3 mg (Phase 1)

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
Investigational mTOR kinase inhibitor
Other Name: INK128

Experimental: Dose Level 2: MLN01283 4 mg (Phase 1)

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
Investigational mTOR kinase inhibitor
Other Name: INK128

Experimental: Dose Level 3: MLN01283 5 mg (Phase 1)

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
Investigational mTOR kinase inhibitor
Other Name: INK128

Experimental: MLN01283 RP2D (Phase 2)

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
Other Name: INK128




Primary Outcome Measures :
  1. 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).

  2. 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.



Information from the National Library of Medicine

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

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 ClinicalTrials.gov identifier (NCT number): NCT02514824


Locations
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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.
Investigators
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Principal Investigator: Robert Haddad, MD Dana-Farber Cancer Institute
  Study Documents (Full-Text)

Documents provided by Robert I. Haddad, MD, Dana-Farber Cancer Institute:
Study Protocol  [PDF] March 18, 2016
No Statistical Analysis Plan (SAP) exists for this study.

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Responsible Party: Robert I. Haddad, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02514824    
Other Study ID Numbers: 15-223
First Posted: August 4, 2015    Key Record Dates
Results First Posted: December 29, 2020
Last Update Posted: December 29, 2020
Last Verified: December 2020
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
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Infections
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue