MLN0128 in Recurrent/Metastatic Merkel Cell Carcinoma

NCT02514824 | Completed Phase 1 Results DMC

• 1 other identifier: 15-223
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Merkel Cell Carcinoma

Keywords

recurrent merkel cell carcinoma; metastatic merkel cell carcinoma

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  The observation period for DLT evaluation was the first 28 days (cycle 1) of treatment.

Study Arms (4)

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.

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.

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.

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.

Drug: MLN0128

Interventions

MLN0128 DRUG

Investigational mTOR kinase inhibitor

Also known as: INK128

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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:

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

sapanisertib

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Limitations and Caveats

The study did not proceed to phase 2 due to slow accrual and lack of efficacy.

Results Point of Contact

• Title: Robert Haddad, MD
• Organization: Dana-Farber Cancer Institute

Robert_Haddad@dfci.harvard.edu

617.632.3090

Study Officials

• Robert Haddad, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 28, 2015
• First Posted: August 4, 2015
• Study Start: October 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: June 1, 2017
• Last Updated: December 29, 2020
• Results First Posted: December 29, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)