Dose-Seeking Study of MPT0E028 in Subjects With Advanced Solid Malignancies Without Standard Treatment

NCT02350868 | Completed Phase 1 DMC

• 1 other identifier: MPT0E028-101
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

The Dose Escalation Phase will determine the MTD of MPT0E028 and evaluate its safety and tolerability, PK, PD, and preliminary clinical effects; the subsequent Dose Confirmation Phase will be a cohort expansion at or below the MTD (i.e., an RP2D) of MPT0E028.

Conditions

Advanced Solid Malignancies

Keywords

without Standard Treatment

Outcome Measures

Primary Outcomes (3)

• the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of daily oral MPT0E028 in subjects with advanced solid malignancies

  Toxicity will be graded and recorded according to National Cancer Institute Common Terminology Criteria for Adverse Events - (CTCAE v4.0). The MTD of MPT0E028 is defined as the highest dose level at which less than 1/3 of subjects experience DLT during Cycle 1 and have 6 subjects in total to confirm the safety of MTD.

  28 days (Cycle 1)

• the pharmacokinetic (PK) profile of MPT0E028 in subjects with advanced solid malignancies

  PK parameters, including area under the curve, maximum plasma concentration, trough plasma concentration, time to maximum plasma concentration, apparent oral clearance, and plasma half-life will be determined.

  baseline; Day 1, 8, 15 of Cycle1; Day 1 and 15 of Cycle 2, 3 and 4 (each cycle is 28 days)

• the pharmacodynamic (PD) effects of MPT0E028 in subjects with advanced solid malignancies through the measurement of the biomarker peripheral blood mononuclear cell (PBMC) histone acetylation

  PBMC histone acetylation status will be assessed.

  baseline; Day 1, 15 of cycle1; Day 1 of Cycle 2, 3 and 4 (each cycle is 28 days)

Study Arms (1)

Arm 1

EXPERIMENTAL

Subjects will be treated with oral doses of MPT0E028 in consecutive, 28-day cycles, and will be evaluated regularly for safety. Subjects who tolerate the drug and who do not experience progressive disease may continue to receive MPT0E028 at the discretion of the principal Investigator for up to 6 cycles.

Drug: MPT0E028

Interventions

MPT0E028 DRUG

The starting dose in the Dose Escalation Phase will be 50 mg/day.Dose escalation from the first cohort to the second cohort will be doubled; and from the second cohort to the fourth cohort will proceed at no more than 50% increments.

Arm 1

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 20 years of age.
• Pathologically confirmed advanced solid tumor, occurring in progressed disease after treatment with standard therapy, and for which standard therapy proven to provide clinical benefit does not exist.
• NOTE: For primary liver cancer, the standard therapies, such as transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA) and percutaneous ethanol intratumor injection (PEI).
• Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤1 (Appendix 1).
• Evaluable disease, either measurable on physical examination (PE) or imaging by Response Evaluation Criteria in Solid Tumors (RECIST v1.1, Appendix 4), or by informative tumor marker(s).
• Laboratory values at screening:
• ANC ≥1,500/mm3;
• Platelets ≥100,000/mm3;
• Total bilirubin ≤1.5 × the upper limit of normal (ULN);
• Aspartate aminotransferase (AST \[SGOT\]) ≤2.5 × the ULN;
• Alanine aminotransferase (ALT \[SGPT\]) ≤2.5 × the ULN;
• Serum creatinine ≤1.5 mg/dL or a measured creatinine clearance ≥60 mL/min; and
• Negative serum beta- hCG test in women of childbearing potential (defined as women ≤50 years of age or history of amenorrhea for ≤12 months prior to study entry).
• Subjects with primary liver cancer or hepatic metastasis are eligible to enroll, provided that, at screening, the following criteria are met:
• Total bilirubin is no higher than the ULN;

You may not qualify if:

• Any chemotherapy, immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless it comprises androgen-deprivation therapy in a subject with prostate cancer and the dose has been stable for 3 months prior to Baseline and will remain stable during the trial), immunosuppressive therapy, corticosteroids \>20 mg/day prednisone or equivalent (unless administered to prevent contrast material reactions during radiographic procedures), or growth factor treatment (e.g., erythropoietin) within 14 days prior to initiation of study drug.
• Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of alopecia or peripheral neuropathy, that has not resolved to ≤Grade 1, as determined by National Cancer Institute CTCAE v 4.0 (http://evs.nci.nih.gov/ftp1/CTCAE/About.html).
• Positive hepatitis B virus surface antigen (HBsAg) or positive anti-hepatitis C virus (HCV) antibody.
• Radiotherapy within 4 weeks prior to baseline.
• Receipt of radiotherapy to \>25 % of bone marrow (Appendix 5).
• Major surgery within 28 days prior to initiation of study drug.
• Life expectancy \<12 weeks.
• Active bacterial, fungal, or viral infection requiring systemic therapy.
• Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.
• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4, Appendix 1), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
• History of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to \>450 msec for males or \>470 msec for females.
• With other previous malignancies prior to study entry, except for
• non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix
• the tumor was treated with curative intent more than 2 years prior to study entry.
• Treatment with the following pharmaceutical or herbal agents within 14 days prior to study drug uptake:

Sponsors & Collaborators

• Taipei Medical University: lead

Study Sites (2)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Medical University Hospital

Taipei, 110, Taiwan

Location

MeSH Terms

Interventions

3-(1-benzenesulfonyl-2,3-dihydro-1H-indol-5-yl)-N-hydroxyacrylamide

Study Officials

• Jing-Ping Liou

  Taipei Medical University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2015
• First Posted: January 30, 2015
• Study Start: April 24, 2015
• Primary Completion: January 19, 2019
• Study Completion: January 19, 2019
• Last Updated: April 11, 2019

Record last verified: 2018-09

Locations

TW (2)