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

NCT03604783 | Terminated Phase 1 FDA Drug

• 1 other identifier: TP-1287-101
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 10

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.

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

Outcome Measures

Primary Outcomes (4)

• 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

  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

  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

  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

  16 weeks

Secondary Outcomes (3)

• During Dose Escalation: Recommended Phase 2 Dose of TP-1287

  23 months

• During Dose Escalation: Determine antitumor activity of TP-1287

  20 months

• During Dose Expansion: Determine the median progression-free survival (PFS) rate in patients with sarcoma

  24 weeks

Study Arms (1)

Single Arm TP-1287

EXPERIMENTAL

TP-1287 by oral administration

Drug: TP-1287

Interventions

TP-1287 DRUG

TP-1287 by oral administration

Single Arm TP-1287

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (10)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

US Oncology - Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

US Oncology - Greenville Health System

Greenville, South Carolina, 29605, United States

Location

US Oncology - Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Sarcoma; Sarcoma, Ewing; Liposarcoma; Sarcoma, Synovial; Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Adipose Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2018
• First Posted: July 27, 2018
• Study Start: December 26, 2018
• Primary Completion: January 10, 2024
• Study Completion: January 10, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)