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

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ClinicalTrials.gov Identifier: NCT03604783
Recruitment Status : Recruiting
First Posted : July 27, 2018
Last Update Posted : May 3, 2021
Sponsor:
Information provided by (Responsible Party):
Sumitomo Dainippon Pharma Oncology, Inc

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Sarcoma Drug: TP-1287 Phase 1

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

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 26, 2018
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Single Arm TP-1287
TP-1287 by oral administration
Drug: TP-1287
TP-1287 by oral administration




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. During Dose Escalation: Recommended Phase 2 Dose of TP-1287 [ Time Frame: 23 months ]
    To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-1287, MTD data to be reviewed

  2. During Dose Escalation: Determine antitumor activity of TP-1287 [ Time Frame: 20 months ]
    Objective radiographic assessment to be performed to determine antitumor activity by modified RECIST criteria

  3. During Dose Expansion: Determine the median progression-free survival (PFS) rate in patients with sarcoma [ Time Frame: 24 weeks ]
    Survival rate without progression



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03604783


Contacts
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Contact: Nissa Ashenbramer, BBA 210-639-2144 nissa.ashenbramer@sdponcology.com
Contact: Susan Smith, MSN 210-414-7702 susan.smith@sdponcology.com

Locations
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United States, California
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Mitchell Gross, MD         
Principal Investigator: Mitchell Gross, MD         
United States, Nevada
US Oncology - Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Nicholas Vogelzang, MD         
Principal Investigator: Nicholas Vogelzang, MD         
United States, South Carolina
US Oncology - Greenville Health System Recruiting
Greenville, South Carolina, United States, 29605
Contact: William Edenfield, MD         
Principal Investigator: William Edenfield, MD         
United States, Texas
US Oncology - Texas Oncology - Tyler Recruiting
Tyler, Texas, United States, 75702
Contact: Donald Richards, MD, PhD         
Principal Investigator: Donald Richards, MD, PhD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Katy C Schroeder, BSN, RN, OCN    414-805-8843      
Principal Investigator: Ben George, MD         
Sponsors and Collaborators
Sumitomo Dainippon Pharma Oncology, Inc
Investigators
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Study Director: Pablo Martinez, MD, PhD Sumitomo Dainippon Pharma Oncology, Inc
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Responsible Party: Sumitomo Dainippon Pharma Oncology, Inc
ClinicalTrials.gov Identifier: NCT03604783    
Other Study ID Numbers: TP-1287-101
First Posted: July 27, 2018    Key Record Dates
Last Update Posted: May 3, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sumitomo Dainippon Pharma Oncology, Inc:
Sumitomo Dainippon Pharma Oncology SDPO
Phase 1
First in human
Advanced Malignancy
Cancer
Metastatic
Sarcoma
Additional relevant MeSH terms:
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Sarcoma
Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type