Advanced Solid MalignanciesPhase 1NCT02350868
Dose-Seeking Study of MPT0E028 in Subjects With Advanced Solid Malignancies Without Standard Treatment
A Phase 1 study testing MPT0E028 in people with Advanced Solid Malignancies, run by Taipei Medical University at 2 sites in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Advanced Solid Malignancies
- What is being tested?
- MPT0E028
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 2 sitesTaiwan
- Study dates
- 24 Apr 2015to 19 Jan 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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;
- AST and ALT are each ≤5 × the ULN;
- Severe liver dysfunction (Child-Pugh Class B or C) is not present; and
- Subjects with a history of esophageal bleeding have varices that have been sclerosed or banded and no bleeding episodes have occurred during the prior 6 months.
- If there is a history of brain metastases treated with radiation therapy, the radiation therapy must have occurred at least 6 weeks prior to enrollment (signed ICF obtained) and the metastatic disease must have been stable since completion.
- Willing and able to provide written Informed Consent and comply with the requirements of the study.
- In addition, subjects enrolled in the Dose Confirmation Phase must have measurable disease, using RECIST v1.1 (Appendix 4).
Who cannot join
- 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.
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- 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:
- known to be moderate or severe inhibitors or inducers of CYP3A4 (Appendix 2).
- known to be sensitive or narrow therapeutic index substrates of CYP3A4, CYP2C8, CYP2C9, or CYP2C19 (Appendix 3)
- Note:
- For Docetaxel, Vincristine, Phenobarbital, and Aripiprazole if the washout period had been performed ≥ 30 days, the subject can be enrolled.
- Subject received Amiodarone will not be enrolled.
- Use of any investigational agents within 4 weeks of baseline.
- Pregnant or lactating female.
- Women of childbearing potential, unless they agree to use dual contraceptive methods which, in the opinion of the principal Investigator, are effective and adequate for that subject's circumstances while on study drug and for 3 months afterward.
- Men who partner with a woman of childbearing potential, unless they agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable, or barrier method) while on study drug and for 3 months afterward.
- Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the Investigator's opinion, would make the subject inappropriate for entry into this study.
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites
National Taiwan University Hospital
Taipei, 100
Taipei Medical University Hospital
Taipei, 110
About this study
Official title: A Phase 1, First-In-Human, Dose-Seeking Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Orally Administered MPT0E028 in Subjects With Advanced Solid Malignancies Without Standard Treatment
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.
Read the detailed description
This is an open-label, non-randomized, dose-escalation study that will evaluate MPT0E028 in subjects with advanced solid malignancies. 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. The Sponsor will keep providing drug for extension cycles to subjects whose disease is controlled at the end of 6th cycle until the end of the study or until the early study termination determined by sponsor. Subjects will return for a follow-up visit 28 days after completion of the end of Study.
- Conditions
- Advanced Solid Malignancies
- Being tested
- MPT0E028
- Keywords
- without Standard Treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MPT0E028Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: MPT0E028 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: baseline; Day 1, 15 of cycle1; Day 1 of Cycle 2, 3 and 4 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2015 (estimated)
- Study start24 Apr 2015
- Primary completion19 Jan 2019
- Study completion19 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid MalignanciesStudies of the same condition, open and under way.
- More trials run by Taipei Medical UniversityThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taipei Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jing-Ping Liou, Study director, Taipei Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02350868
- Sponsor's protocol ID
- MPT0E028-101
- Status last verified
- Sep 2018
- First submitted
- 13 Jan 2015
- Last updated
- 11 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, First-In-Human, Dose-Seeking Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Orally Administered MPT0E028 in Subjects With Advanced Solid Malignancies Without Standard Treatment
- ClinicalTrials.gov ID
- NCT02350868
- Acronym / sponsor ID
- MPT0E028-101
- Conditions
- Advanced Solid Malignancies
- Keywords
- without Standard Treatment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Taipei Medical UniversityUniversity, hospital or other
- Study start
- 24 Apr 2015 (actual)
- Primary completion
- 19 Jan 2019 (actual)
- Study completion
- 19 Jan 2019 (actual)
- First posted
- 30 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an open-label, non-randomized, dose-escalation study that will evaluate MPT0E028 in subjects with advanced solid malignancies. 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. The Sponsor will keep providing drug for extension cycles to subjects whose disease is controlled at the end of 6th cycle until the end of the study or until the early study termination determined by sponsor. Subjects will return for a follow-up visit 28 days after completion of the end of Study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: MPT0E028Subjects 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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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).
Key exclusion criteria (25 listed)
- 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).
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 |
|---|---|---|
| MPT0E028The 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. | Drug | Arm 1 |
Primary outcome
the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of daily oral MPT0E028 in subjects with advanced solid malignancies
Time frame: 28 days (Cycle 1)
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.
the pharmacokinetic (PK) profile of MPT0E028 in subjects with advanced solid malignancies
Time frame: baseline; Day 1, 8, 15 of Cycle1; Day 1 and 15 of Cycle 2, 3 and 4 (each cycle is 28 days)
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.
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
Time frame: baseline; Day 1, 15 of cycle1; Day 1 of Cycle 2, 3 and 4 (each cycle is 28 days)
PBMC histone acetylation status will be assessed.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2019.
- Individual participant dataSharing planned: Undecided
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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.
Jing-Ping Liou study director
Taipei Medical University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MPT0E028 in people with Advanced Solid Malignancies, run by Taipei Medical University at 2 sites in Taiwan.
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 21 inclusion and 25 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 11 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of daily oral MPT0E028 in subjects with advanced solid malignancies (time frame: 28 days (Cycle 1)). The study lists 3 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 11 Apr 2019.