Advanced Solid TumorsPhase 1NCT03429218
First-in-human Study of Oral TP-0184 in Patients With Advanced Solid Tumors
A Phase 1 study testing TP-0184 in people with Advanced Solid Tumors, run by Sumitomo Pharma America, Inc. at 5 sites in United States.
Trial summary
TP-0184 is a potent inhibitor of ALK2 or ACRV1 kinase, a constitutively active serine/threonine receptor kinase due to activating mutations or upregulated upstream signaling pathways. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- TP-0184
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 5 sitesUnited States
- Study dates
- 10 Jul 2018to 8 Mar 2021
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor
- Be refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition.
- Have one or more tumors measurable or evaluable as outlined by modified RECIST v1.1
- Have an Eastern Cooperative Oncology Group (ECOG) (World Health Organization [WHO]) performance of ≤1
- Have a life expectancy ≥3 months
- Be ≥18 years of age
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- Have a negative pregnancy test (if female of childbearing potential)
- Have acceptable liver function:
- Bilirubin ≤1.5x upper limit of normal (ULN)
- Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase ≤2.5x upper limit of normal (ULN) *If liver metastases are present, then ≤5x ULN is allowed.
- Have acceptable renal function: Calculated creatinine clearance ≥ 30 mL/min
- Have acceptable hematologic status:
- Granulocyte ≥1500 cells/mm3
- Platelet count ≥100,000 (plt/mm3)
- Hemoglobin ≥8 g/dL (Patients may not have received prior transfusions within 2 weeks of the first dose of TP-0184)
- Have acceptable coagulation status:
- Prothrombin time (PT) within 1.5x normal limits
- Activated partial thromboplastin time (aPTT) within 1.5x normal limits
- Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation and for at least 3 months (males) and 6 months (females) after the last study drug dose. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Have read and signed the Institutional Review Board (IRB)-approved informed consent form (ICF) prior to any study related procedure. (In the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new ICF must be signed.)
Who cannot join
- History of congestive heart failure (CHF); cardiac disease, myocardial infarction within the past 6 months prior to Cycle 1 Day 1; left ventricular ejection fraction (LVEF) <45% by echocardiogram (ECHO), unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1 Day 1
- Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450 msec in men and >470 msec in women
- Have a seizure disorder requiring anticonvulsant therapy
- Presence of symptomatic central nervous system metastatic disease or disease that requires local therapy such as radiotherapy, surgery, or increasing dose of steroids within the prior 2 weeks
- Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting O2 saturation of ≤90% breathing room air)
- Have undergone major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1
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- Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Are pregnant or nursing
- Received treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 28 days or 5 half lives, whichever occurs first, prior to study entry (6 weeks for nitrosoureas or Mitomycin C)
- Are unwilling or unable to comply with procedures required in this protocol
- Have known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Patients with history of chronic hepatitis that is currently not active are eligible.
- Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
- Are currently receiving any other investigational agent
- Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation
- Have undergone significant surgery to the gastrointestinal tract that could impair absorption or that could result in short bowel syndrome with diarrhea due to malabsorption
- Have hemochromatosis or a transferrin saturation (TS) >50% in men or >45% in women at baseline or noted during the study via scheduled iron panel monitoring
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Northside Hospital
Atlanta, Georgia, 30342
Massachusetts General Hospital MGH
Boston, Massachusetts, 02215
University of Texas Southwestern UTSW
Dallas, Texas, 75390-9179
University of Kansas Medical Center Research Institute
Kansas City, Kansas, 66160
Honor Health
Scottsdale, Arizona, 85258
About this study
Official title: A Phase I, First-in-human, Open-label, Dose-escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-0184 Administered Once Weekly for 4 Weeks to Patients With Advanced Solid Tumors
TP-0184 is a potent inhibitor of ALK2 or ACRV1 kinase, a constitutively active serine/threonine receptor kinase due to activating mutations or upregulated upstream signaling pathways. This is a Phase 1, open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study, with a purpose of determining the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-0184 administered once weekly for 4 weeks in patients with advanced solid tumors.
Read the detailed description
Primary Objective:
- To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-0184 administered once weekly for 4 weeks, over a range of doses in patients with advanced solid tumors.
Secondary Objectives:
- To establish the pharmacokinetics of orally administered TP-0184
- To observe patients for any evidence of antitumor activity of TP-0184 by objective radiographic assessment
- To study the pharmacodynamics of TP-0184 therapy
- To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-0184
- Conditions
- Advanced Solid Tumors
- Being tested
- TP-0184
- Keywords
- Sumitomo Dainippon Pharma Oncology SDPO, Phase 1, First in human, Solid Tumors, Advanced Malignancy, Cancer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TP-0184Drug
Oral dose once weekly for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Single Arm TP-0184 | Experimental | Weekly dose of TP-0184 by oral administration Receives: Drug: TP-0184 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events
A DLT is defined as any one of the following events observed within Cycle 1 regardless of investigator attribution unless there is a clear alternative explanation:
- Grade 3 or greater febrile neutropenia
- Grade 4 neutropenia for ≥7 consecutive days
- Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with clinically significant bleeding or that requires a platelet transfusion
- Grade 3 or 4 nonhematologic AEs including nausea, vomiting, diarrhea, and electrolyte imbalances persisting for more than 48 hours despite optimal medical management
- Dosing delays ≥1 week due to treatment emergent adverse events or related severe laboratory test values
Measured: Day 1 - 28
Determine maximum tolerated dose (MTD)
If a patient experiences a DLT, up to three additional patients will be treated at that dose level. If no additional DLTs are observed in the expanded six-patient cohort, the dose will be escalated in a new cohort of three patients. If two or more patients at a given dose level experience a DLT during the first cycle, then the MTD will have been exceeded and up to a total of six patients will be treated at the next lower dose level. If 0 or 1 of 6 patients experiences a DLT at this previous lower dose level, this dose will be declared the MTD.
Measured: 20 months
Secondary outcomes (2)
Recommended Phase 2 Dose of TP-0184
To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-0184, MTD data to be reviewed
Measured: 23 months
Determine antitumor activity of TP-0184
Objective radiographic assessment to be performed to determine antitumor activity by modified RECIST criteria
Measured: 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2018
- Study start10 Jul 2018
- Primary completion8 Mar 2021
- Study completion8 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- 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
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sumitomo Pharma America, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Greg Pennock, MD, Study director, Sumitomo Pharma America, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03429218
- Sponsor's protocol ID
- TP-0184-101
- Status last verified
- Nov 2023
- First submitted
- 5 Feb 2018
- Last updated
- 14 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, First-in-human, Open-label, Dose-escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-0184 Administered Once Weekly for 4 Weeks to Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03429218
- Acronym / sponsor ID
- TP-0184-101
- Conditions
- Advanced Solid Tumors
- Keywords
- Sumitomo Dainippon Pharma Oncology SDPO, Phase 1, First in human, Solid Tumors, Advanced Malignancy, Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Sumitomo Pharma America, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Jul 2018 (actual)
- Primary completion
- 8 Mar 2021 (actual)
- Study completion
- 8 Mar 2021 (actual)
- First posted
- 12 Feb 2018 (actual)
- 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.
TP-0184 is a potent inhibitor of ALK2 or ACRV1 kinase, a constitutively active serine/threonine receptor kinase due to activating mutations or upregulated upstream signaling pathways. This is a Phase 1, open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study, with a purpose of determining the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-0184 administered once weekly for 4 weeks in patients with advanced solid tumors.
Detailed description
Primary Objective:
- To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-0184 administered once weekly for 4 weeks, over a range of doses in patients with advanced solid tumors.
Secondary Objectives:
- To establish the pharmacokinetics of orally administered TP-0184
- To observe patients for any evidence of antitumor activity of TP-0184 by objective radiographic assessment
- To study the pharmacodynamics of TP-0184 therapy
- To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-0184
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm TP-0184 | Experimental | Drug: TP-0184Weekly dose of TP-0184 by oral administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor
- Be refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition.
- Have one or more tumors measurable or evaluable as outlined by modified RECIST v1.1
- Have an Eastern Cooperative Oncology Group (ECOG) (World Health Organization [WHO]) performance of ≤1
- Have a life expectancy ≥3 months
Key exclusion criteria (16 listed)
- History of congestive heart failure (CHF); cardiac disease, myocardial infarction within the past 6 months prior to Cycle 1 Day 1; left ventricular ejection fraction (LVEF) <45% by echocardiogram (ECHO), unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1 Day 1
- Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450 msec in men and >470 msec in women
- Have a seizure disorder requiring anticonvulsant therapy
- Presence of symptomatic central nervous system metastatic disease or disease that requires local therapy such as radiotherapy, surgery, or increasing dose of steroids within the prior 2 weeks
- Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting O2 saturation of ≤90% breathing room air)
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 |
|---|---|---|
| TP-0184Oral dose once weekly for 4 weeks | Drug | Single Arm TP-0184 |
Primary outcome
Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events
Time frame: Day 1 - 28
A DLT is defined as any one of the following events observed within Cycle 1 regardless of investigator attribution unless there is a clear alternative explanation: * Grade 3 or greater febrile neutropenia * Grade 4 neutropenia for ≥7 consecutive days * Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with clinically significant bleeding or that requires a platelet transfusion * Grade 3 or 4 nonhematologic AEs including nausea, vomiting, diarrhea, and electrolyte imbalances persisting for more than 48 hours despite optimal medical management * Dosing delays ≥1 week due to treatment emergent adverse events or related severe laboratory test values
Determine maximum tolerated dose (MTD)
Time frame: 20 months
If a patient experiences a DLT, up to three additional patients will be treated at that dose level. If no additional DLTs are observed in the expanded six-patient cohort, the dose will be escalated in a new cohort of three patients. If two or more patients at a given dose level experience a DLT during the first cycle, then the MTD will have been exceeded and up to a total of six patients will be treated at the next lower dose level. If 0 or 1 of 6 patients experiences a DLT at this previous lower dose level, this dose will be declared the MTD.
2 secondary outcomes
Recommended Phase 2 Dose of TP-0184
Time frame: 23 months
Determine antitumor activity of TP-0184
Time frame: 20 months
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 14 Nov 2023.
- Individual participant dataSharing planned: No
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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.
Greg Pennock, MD study director
Sumitomo Pharma America, Inc.
5 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 TP-0184 in people with Advanced Solid Tumors, run by Sumitomo Pharma America, Inc. at 5 sites in United States.
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 20 inclusion and 16 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 14 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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?
Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events (time frame: Day 1 - 28). The study lists 2 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 14 Nov 2023.