Advanced Solid TumorsPhase 1NCT03604783
Phase 1, First-in-human Study of Oral TP-1287 in Patients with Advanced Solid Tumors
A Phase 1 study testing TP-1287 in people with Advanced Solid Tumors and Sarcoma, run by Sumitomo Pharma America, Inc. at 10 sites in United States.
Trial summary
TP-1287 is an oral phosphate prodrug of the CDK9 inhibitor, alvocidib. This is a Phase 1, open-label, dose-escalation, dose-expansion, safety, pharmacokinetics, and pharmacodynamic study, with a purpose of determining the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-1287 in patients with… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Advanced Solid Tumors, Sarcoma, Ewing Sarcoma
- What is being tested?
- TP-1287
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 10 sitesUnited States
- Study dates
- 26 Dec 2018to 10 Jan 2024
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- For Dose Escalation:
- Have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor excluding tumor types with rapid cell turnover, ie, small cell cancer (lung and extra pulmonary), inflammatory breast cancer (IBC), medulloblastoma, neuroblastoma and melanoma with extensive liver metastasis (greater than or equal to 50% of the liver involved; patients with melanoma and metastasis to less than 50% of the liver are eligible)
- Be refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition.
- For Dose Expansion:
- Patients who have histologically confirmed locally advanced or metastatic unresectable Ewing sarcoma
- Have received at least one prior line of treatment (but no more than 5 prior lines) including an anthracycline.
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- Have one or more measurable tumors measurable or evaluable as outlined by modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1
- Have a life expectancy greater than or equal to 3 months at the time of informed consent/assent.
- Be greater than or equal to 18 years of age for dose escalation and expansion; Patients with Ewing sarcoma aged ≥ 12 years may also participate in dose expansion if they weigh ≥40 kg
- Have a negative pregnancy test (if female of childbearing potential)
- Have acceptable liver function:
- Bilirubin less than or equal to 1.5x upper limit of normal (ULN) (unless attributed to Gilbert's syndrome)
- Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase less than or equal to 2.5x upper limit of normal (ULN) *If liver metastases are present, then less than or equal to 5x ULN is allowed.
- If bone metastases are present, but bilirubin, AST, ALT are ≤2.5x ULN, then there is no upper limit for alkaline phosphatase level. Radiographic proof of bone involvement is required, and alkaline phosphatase fractionation is strongly recommended to confirm the elevation is due to bony metastases.
- Have acceptable renal function:
- Calculated creatinine clearance greater than or equal to 30 mL/min
- Have acceptable hematologic status:
- Granulocyte greater than or equal to 1500 cells/mm3
- Platelet count greater than or equal to 100,000 (plt/mm3)
- Hemoglobin greater than or equal to 8 g/dl
- 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 a highly effective method of contraception prior to study entry and for the duration of study participation including for at least 3 months (males) and 6 months (females) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Male patients must agree not to donate sperm during the study and for 3 months after the last dose of TP-1287 due to unknown risks and potential harm to an unborn child/infant.
- Female patients must agree not to donate eggs during the study and for 6 months after the last dose of TP-1287 due to unknown risks and potential harm to an unborn child/infant.
- 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.) Assent is also required for patients who have not attained the legal age of consent for treatments or procedures involved in research.
Who cannot join
- History of congestive heart failure (CHF), greater than New York Heart Association (NYHA) Class III, myocardial infarction within the past 6 months prior to Cycle 1 Day 1, left ventricular ejection fraction (LVEF) less than 45% by echocardiogram (ECHO) or multigated acquisition scan (MUGA), uncontrolled 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. Patients with previously treated and/or controlled metastasis are eligible.
- Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting 02 saturation of less than or equal to 90% breathing room air)
- Have undergone major 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 surgery, chemotherapy, or investigational therapy within 28 days or 5 half-lives, whichever occurs first, prior to first administration of study drug (6 weeks for nitrosoureas or Mitomycin C) and 2 weeks for radiation therapy.
- 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 (e.g., 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 symptomatic malabsorption conditions (eg, Crohn's disease, etc) or 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
US Oncology - Greenville Health System
Greenville, South Carolina, 29605
US Oncology - Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Memorial Sloan Kettering
New York, New York, 10065
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
US Oncology - Texas Oncology - Tyler
Tyler, Texas, 75702
About this study
Official title: A Phase 1, First-in-human, Open-label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-1287 to Patients with Advanced Solid Tumors
TP-1287 is an oral phosphate prodrug of the CDK9 inhibitor, alvocidib. This is a Phase 1, open-label, dose-escalation, dose-expansion, safety, pharmacokinetics, and pharmacodynamic study, with a purpose of determining the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-1287 in patients with advanced metastatic or progressive solid tumors who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition.
Read the detailed description
Primary Objective:
- During Dose Escalation: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-1287 in patients with advanced metastatic or progressive solid tumors who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition.
- During Dose Escalation: To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-1287
- During Dose Expansion: To evaluate the preliminary antitumor activity of TP-1287 in terms of objective response rate (ORR) when administered at the RP2D in patients with sarcoma subtypes (ie, EWS, DDLPS and SS)
- During Dose Expansion: To evaluate the preliminary antitumor activity of TP-1287 in terms of clinical benefit rate (CBR) at week 16 when administered at the RP2D in patients with the defined sarcoma subtypes
Secondary Objectives:
- During Dose Escalation: To establish the pharmacokinetics of orally administered TP-1287
- During Dose Escalation: To observe patients for any evidence of antitumor activity of TP-1287 by objective radiographic assessment
- During Dose Escalation: To study the pharmacodynamics of TP-1287 therapy
- During Dose Expansion: To determine the median progression-free survival (PFS) rate in patients with sarcoma
- During Dose Expansion: To evaluate the safety of TP-1287 when administered at the RP2D in patients with sarcoma
- Conditions
- Advanced Solid Tumors, Sarcoma, Ewing Sarcoma, Dedifferentiated Liposarcoma, Synovial Sarcoma
- Being tested
- TP-1287
- Keywords
- Sumitomo Pharma Oncology SMPO, Phase 1, First in human, Advanced Malignancy, Cancer, Metastatic, Sarcoma, Ewing
- Medical subject headings
- Sarcoma, Sarcoma, Ewing, Liposarcoma, Sarcoma, Synovial, Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TP-1287Drug
TP-1287 by oral administration
| Study group | Role | What they receive |
|---|---|---|
| Single Arm TP-1287 | Experimental | TP-1287 by oral administration Receives: Drug: TP-1287 |
What is being measured
The primary outcome is the main question the study is designed to answer.
During Dose Escalation: Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events
A DLT is defined as a drug-related toxicity that is observed to occur within the first 28 days of treatment
Measured: 21 days
During Dose Escalation: Determine maximum tolerated dose (MTD)
MTD will be determined based upon toxicity grades which are defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Measured: 20 months
During Dose Expansion: Determine preliminary antitumor activity of TP-1287 in terms of objective response rate (ORR) when administered at the Recommended Phase 2 Dose (RP2D) in patients with sarcoma
Objective radiographic assessment to be performed to determine antitumor activity by modified RECIST criteria
Measured: 20 months
During Dose Expansion: Determine preliminary antitumor activity of TP-1287 in terms of clinical benefit rate (CBR) at week 16 when administered at the RP2D in patients with sarcoma.
Clinical benefit rate assessment is to be performed for all patients with measureable disease at baseline by modified RECIST criteria, who achieve a CR, PR or SD and sustain the response for more than 16 weeks
Measured: 16 weeks
Secondary outcomes (3)
During Dose Escalation: Recommended Phase 2 Dose of TP-1287
To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-1287, MTD data to be reviewed
Measured: 23 months
During Dose Escalation: Determine antitumor activity of TP-1287
Objective radiographic assessment to be performed to determine antitumor activity by modified RECIST criteria
Measured: 20 months
During Dose Expansion: Determine the median progression-free survival (PFS) rate in patients with sarcoma
Survival rate without progression
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2018
- Study start26 Dec 2018
- Primary completion10 Jan 2024
- Study completion10 Jan 2024
Why it stopped: Sponsor's decision to terminate further development of the program.
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
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sumitomo Pharma America, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03604783
- Sponsor's protocol ID
- TP-1287-101
- Status last verified
- Sep 2024
- First submitted
- 18 Jul 2018
- Last updated
- 19 Sep 2024
- 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 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, First-in-human, Open-label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-1287 to Patients with Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03604783
- Acronym / sponsor ID
- TP-1287-101
- Conditions
- Advanced Solid Tumors, Sarcoma, Ewing Sarcoma, Dedifferentiated Liposarcoma, Synovial Sarcoma
- Keywords
- Sumitomo Pharma Oncology SMPO, Phase 1, First in human, Advanced Malignancy, Cancer, Metastatic, Sarcoma, Ewing
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision to terminate further development of the program.
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Sumitomo Pharma America, Inc.Industry (pharma, biotech, devices)
- Study start
- 26 Dec 2018 (actual)
- Primary completion
- 10 Jan 2024 (actual)
- Study completion
- 10 Jan 2024 (actual)
- First posted
- 27 Jul 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-1287 is an oral phosphate prodrug of the CDK9 inhibitor, alvocidib. This is a Phase 1, open-label, dose-escalation, dose-expansion, safety, pharmacokinetics, and pharmacodynamic study, with a purpose of determining the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-1287 in patients with advanced metastatic or progressive solid tumors who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition.
Detailed description
Primary Objective:
- During Dose Escalation: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-1287 in patients with advanced metastatic or progressive solid tumors who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition.
- During Dose Escalation: To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-1287
- During Dose Expansion: To evaluate the preliminary antitumor activity of TP-1287 in terms of objective response rate (ORR) when administered at the RP2D in patients with sarcoma subtypes (ie, EWS, DDLPS and SS)
- During Dose Expansion: To evaluate the preliminary antitumor activity of TP-1287 in terms of clinical benefit rate (CBR) at week 16 when administered at the RP2D in patients with the defined sarcoma subtypes
Secondary Objectives:
- During Dose Escalation: To establish the pharmacokinetics of orally administered TP-1287
- During Dose Escalation: To observe patients for any evidence of antitumor activity of TP-1287 by objective radiographic assessment
- During Dose Escalation: To study the pharmacodynamics of TP-1287 therapy
- During Dose Expansion: To determine the median progression-free survival (PFS) rate in patients with sarcoma
- During Dose Expansion: To evaluate the safety of TP-1287 when administered at the RP2D in patients with sarcoma
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-1287 | Experimental | Drug: TP-1287TP-1287 by oral administration |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (28 listed)
- For Dose Escalation:
- For Dose Expansion:
- Have one or more measurable tumors measurable or evaluable as outlined by modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1
- Have a life expectancy greater than or equal to 3 months at the time of informed consent/assent.
Key exclusion criteria (15 listed)
- History of congestive heart failure (CHF), greater than New York Heart Association (NYHA) Class III, myocardial infarction within the past 6 months prior to Cycle 1 Day 1, left ventricular ejection fraction (LVEF) less than 45% by echocardiogram (ECHO) or multigated acquisition scan (MUGA), uncontrolled 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. Patients with previously treated and/or controlled metastasis are eligible.
- Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting 02 saturation of less than or equal to 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-1287TP-1287 by oral administration | Drug | Single Arm TP-1287 |
Primary outcome
During Dose Escalation: Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events
Time frame: 21 days
A DLT is defined as a drug-related toxicity that is observed to occur within the first 28 days of treatment
During Dose Escalation: Determine maximum tolerated dose (MTD)
Time frame: 20 months
MTD will be determined based upon toxicity grades which are defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
During Dose Expansion: Determine preliminary antitumor activity of TP-1287 in terms of objective response rate (ORR) when administered at the Recommended Phase 2 Dose (RP2D) in patients with sarcoma
Time frame: 20 months
Objective radiographic assessment to be performed to determine antitumor activity by modified RECIST criteria
During Dose Expansion: Determine preliminary antitumor activity of TP-1287 in terms of clinical benefit rate (CBR) at week 16 when administered at the RP2D in patients with sarcoma.
Time frame: 16 weeks
Clinical benefit rate assessment is to be performed for all patients with measureable disease at baseline by modified RECIST criteria, who achieve a CR, PR or SD and sustain the response for more than 16 weeks
3 secondary outcomes
During Dose Escalation: Recommended Phase 2 Dose of TP-1287
Time frame: 23 months
During Dose Escalation: Determine antitumor activity of TP-1287
Time frame: 20 months
During Dose Expansion: Determine the median progression-free survival (PFS) rate in patients with sarcoma
Time frame: 24 weeks
Results and safety
The study was stopped early (reason given: Sponsor's decision to terminate further development of the program.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
10 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-1287 in people with Advanced Solid Tumors and Sarcoma, run by Sumitomo Pharma America, Inc. at 10 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 28 inclusion and 15 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: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 was stopped early (reason given: Sponsor's decision to terminate further development of the program.). Results are not available in the source record.
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?
During Dose Escalation: Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events (time frame: 21 days). The study lists 4 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 19 Sep 2024; AzTrials last refreshed its copy on 26 Oct 2026.