Study of ON 123300 in Patients With Advanced Cancer

NCT04739293 | Unknown Phase 1 FDA Drug

• 1 other identifier: 19-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

This study will investigate the safety of the drug ON 123300 at increasing doses to determine the best dose to use in future clinical trials.

Conditions

Solid Tumors, Adult

Outcome Measures

Primary Outcomes (3)

• Incidence of Dose Limiting Toxicities (DLT)

  Incidence of protocol defined toxicities that would result in stopping dosing

  First 28 days of dosing

• Incidence of adverse events (AE)

  Adverse events as measured by CTCAE version 5.0

  Consent to 30 days after last dose

• Abnormal Laboratory Test results

  Changes and trends in standard hematology and chemistry blood tests

  Consent to 30 days after last dose

Secondary Outcomes (7)

• Establish the recommended phase 2 dose (RP2D)

  First 28 day cycle

• Pharmacokinetics of ON 123300 and 2 metabolites - Cmax

  Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)

• Pharmacokinetics of ON 123300 and 2 metabolites - Tmax

  Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)

• Pharmacokinetics of ON 123300 and 2 metabolites - AUClast

  Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)

• Pharmacokinetics of ON 123300 and 2 metabolites - T1/2

  Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)

Other Outcomes (1)

• Preliminary efficacy of ON 123300

  Through study completion, an average of 6 months

Study Arms (1)

ON 123300

EXPERIMENTAL

ON 123300 capsules at increasing doses per cohort, starting at 40 mg

Drug: ON123300

Interventions

ON123300 DRUG

ON 123300 hard gelatin capsules

Also known as: HX 301

ON 123300

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age the time of signing the informed consent form (ICF);
• Histological or cytological evidence of advanced and/or metastatic cancer,
• For Dose Escalation Cohorts, patients with measurable or non-measurable disease;
• For RP2D Expansion Cohort, patients with measurable disease;
• Patients must have received and failed at least one prior approved treatment, or have no therapeutic options available as deemed appropriate by their treating physician;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of \< 2;
• Life expectancy of \> 3 months;
• Patients must be able to swallow oral capsules;
• Women of child-bearing potential must have a negative serum screening for pregnancy within 14 days prior to screening. Women and men of child-bearing potential must agree to use highly effective methods of birth control before entry and throughout the study, for up to 12 weeks following the last dose of ON 123300.
• Patients must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted;
• Patients must have the ability to understand the nature of the study and any hazards of participating in the study and communicate satisfactorily with the investigator to participate in the study.
• Patients must be willing and able to adhere and comply to the requirements of the entire study including study visit schedule and other protocol requirements;
• Have adequate organ function, including:
• a. Hematologic: i. absolute neutrophil count (ANC) ≥1.0 × 109/Liter (L) ii. platelets ≥100 × 109/L, and iii. hemoglobin ≥8 g/deciliter (dL). b. Hepatic: i. Total bilirubin ≤1.5 times the upper limit of normal (ULN) and ii. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 times ULN (or ALT and AST ≤5 times ULN if liver metastases are present).
• c. Renal: i. Serum creatinine ≤1.5 times ULN. or estimated creatinine clearance (calculated according to normal institutional practice) greater than 50 ml/min.

You may not qualify if:

• Patients that have any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study or present an unacceptable risk to the patient;
• Patients at risk for Torsades de pointes (TdP):
• Who have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>480 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction formula, or
• who have a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or
• who are currently taking medications that prolong the QT/QTc interval;
• Patients with a diagnosis of hematological malignancies except for non-Hodgkin's lymphoma;
• Have received recent chemotherapy, hormonal therapy, other targeted cancer treatment, or investigational therapy within 14 days of planned first dose;
• Patients currently taking or within 5 half-lives of taking strong inducers and inhibitors of CYP2C8 and CYP3A4;
• History of allergic reaction attributed to compounds of similar chemical or biologic composition/structure to ON 123300 (e.g. prior CDK4/6 inhibitors);
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, bleeding, congestive heart failure, unstable angina, cardiac arrhythmia, oxygen-dependent lung disease, psychiatric illness/social situations that limit participation compliance with study procedures and requirements;
• Patients with a recent history of venous thromboembolic events, defined as event occurring ≤ 6 months prior to screening and also currently on therapy;
• Patients with baseline Grade ≥ 2 diarrhea;
• Patients with Grade ≥ 3 hypercalcemia (Corrected serum calcium \> 12.5 mg/dL);
• Pregnant or nursing mothers;
• Have had major surgery within 14 days prior to screening to allow for post-operative healing of the surgical wound and site(s).

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (3)

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Greenville Health System, Institute for Oncology Clinical Research

Greenville, South Carolina, 29605, United States

RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

RECRUITING

MeSH Terms

Interventions

ON123300

Study Officials

• Michael E Saunders, MD

  Onconova Therapeutics

  STUDY DIRECTOR

Study Design

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

Model Details: 3+3 dose escalation design with expansion cohort at recommended phase 2 dose

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 4, 2021
• Study Start: May 13, 2021
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: December 7, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)