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Phase 1, First-in-human Study of Oral TP-1287 in Patients With Advanced Solid Tumors

Primary Purpose

Advanced Solid Tumors, Sarcoma, Ewing Sarcoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TP-1287
Sponsored by
Sumitomo Pharma America, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumors focused on measuring Sumitomo Pharma Oncology SMPO, Phase 1, First in human, Advanced Malignancy, Cancer, Metastatic, Sarcoma, Ewing

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. For Dose Escalation:

    1. 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)
    2. Be refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition.
  2. For Dose Expansion:

    1. Patients who have a histologically confirmed locally advanced or metastatic unresectable sarcoma
    2. Have received at least one prior line of treatment (but no more than 3 prior lines) including an anthracycline.
  3. Have one or more measurable tumors measurable or evaluable as outlined by modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1
  5. Have a life expectancy greater than or equal to 3 months at the time of informed consent/assent.
  6. Be greater than or equal to 18 years of age for dose escalation and expansion; Patients aged 16 and 17 may also participate in dose expansion if they weigh ≥40 kg
  7. Have a negative pregnancy test (if female of childbearing potential)
  8. Have acceptable liver function:

    1. Bilirubin less than or equal to 1.5x upper limit of normal (ULN) (unless attributed to Gilbert's syndrome)
    2. 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.
  9. Have acceptable renal function:

    a. Calculated creatinine clearance greater than or equal to 30 mL/min

  10. Have acceptable hematologic status:

    1. Granulocyte greater than or equal to 1500 cells/mm3
    2. Platelet count greater than or equal to 100,000 (plt/mm3)
    3. Hemoglobin greater than or equal to 8 g/dl
  11. Have acceptable coagulation status:

    1. Prothrombin time (PT) within 1.5x normal limits
    2. Activated partial thromboplastin time (aPTT) within 1.5x normal limits
  12. 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 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.
  13. 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.

Exclusion Criteria:

  1. 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
  2. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450 msec in men and >470 msec in women
  3. Have a seizure disorder requiring anticonvulsant therapy
  4. 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.
  5. Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting 02 saturation of less than or equal to 90% breathing room air)
  6. Have undergone major surgery within 2 weeks prior to Cycle 1 Day 1
  7. Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy, including known, active COVID-19
  8. Are pregnant or nursing
  9. Received treatment with 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) and 2 weeks for radiation therapy.
  10. Are unwilling or unable to comply with procedures required in this protocol
  11. 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.
  12. 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
  13. Are currently receiving any other investigational agent
  14. Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation
  15. 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

Sites / Locations

  • USC Norris Comprehensive Cancer CenterRecruiting
  • University of Miami Sylvester Comprehensive Cancer CenterRecruiting
  • Massachusetts General HospitalRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • US Oncology - Comprehensive Cancer Centers of Nevada
  • Memorial Sloan KetteringRecruiting
  • Fox Chase Cancer CenterRecruiting
  • US Oncology - Greenville Health System
  • US Oncology - Texas Oncology - Tyler
  • Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm TP-1287

Arm Description

TP-1287 by oral administration

Outcomes

Primary Outcome Measures

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
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
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
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

Secondary Outcome Measures

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
During Dose Escalation: Determine antitumor activity of TP-1287
Objective radiographic assessment to be performed to determine antitumor activity by modified RECIST criteria
During Dose Expansion: Determine the median progression-free survival (PFS) rate in patients with sarcoma
Survival rate without progression

Full Information

First Posted
July 18, 2018
Last Updated
December 12, 2022
Sponsor
Sumitomo Pharma America, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03604783
Brief Title
Phase 1, First-in-human Study of Oral TP-1287 in Patients With Advanced Solid Tumors
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 26, 2018 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sumitomo Pharma America, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single Arm TP-1287
Arm Type
Experimental
Arm Description
TP-1287 by oral administration
Intervention Type
Drug
Intervention Name(s)
TP-1287
Intervention Description
TP-1287 by oral administration
Primary Outcome Measure Information:
Title
During Dose Escalation: Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events
Description
A DLT is defined as a drug-related toxicity that is observed to occur within the first 28 days of treatment
Time Frame
21 days
Title
During Dose Escalation: Determine maximum tolerated dose (MTD)
Description
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
Time Frame
20 months
Title
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
Description
Objective radiographic assessment to be performed to determine antitumor activity by modified RECIST criteria
Time Frame
20 months
Title
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.
Description
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
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
During Dose Escalation: Recommended Phase 2 Dose of TP-1287
Description
To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-1287, MTD data to be reviewed
Time Frame
23 months
Title
During Dose Escalation: Determine antitumor activity of TP-1287
Description
Objective radiographic assessment to be performed to determine antitumor activity by modified RECIST criteria
Time Frame
20 months
Title
During Dose Expansion: Determine the median progression-free survival (PFS) rate in patients with sarcoma
Description
Survival rate without progression
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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: a. 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. Exclusion Criteria: 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Holly Beever, BBA
Phone
210-365-9014
Email
holly.beever@oncology.sumitomo-pharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Susan Smith, MSN
Phone
210-414-7702
Email
susan.smith@oncology.sumitomo-pharma.com
Facility Information:
Facility Name
USC Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Hu, MD
First Name & Middle Initial & Last Name & Degree
James Hu, MD
Facility Name
University of Miami Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gina D'Amato, MD
First Name & Middle Initial & Last Name & Degree
Gina D'Amato, MD
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gregory Cote, MD, PhD
First Name & Middle Initial & Last Name & Degree
Gregory Cote, MD, PhD
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Wagner, MD, PhD
First Name & Middle Initial & Last Name & Degree
Andrew Wagner, MD, PhD
Facility Name
US Oncology - Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Individual Site Status
Completed
Facility Name
Memorial Sloan Kettering
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Dickson, MD
First Name & Middle Initial & Last Name & Degree
Mark Dickson, MD
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margaret von Mehren, MD
First Name & Middle Initial & Last Name & Degree
Margaret von Mehren, MD
Facility Name
US Oncology - Greenville Health System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Individual Site Status
Completed
Facility Name
US Oncology - Texas Oncology - Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Individual Site Status
Completed
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ben George, MD
First Name & Middle Initial & Last Name & Degree
John Charlson, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Phase 1, First-in-human Study of Oral TP-1287 in Patients With Advanced Solid Tumors

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