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Study of ON 123300 in Patients With Advanced Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04739293
Recruitment Status : Recruiting
First Posted : February 4, 2021
Last Update Posted : January 28, 2022
Sponsor:
Information provided by (Responsible Party):
Onconova Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE January 29, 2021
First Posted Date  ICMJE February 4, 2021
Last Update Posted Date January 28, 2022
Actual Study Start Date  ICMJE May 13, 2021
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2021)
  • Incidence of Dose Limiting Toxicities (DLT) [ Time Frame: First 28 days of dosing ]
    Incidence of protocol defined toxicities that would result in stopping dosing
  • Incidence of adverse events (AE) [ Time Frame: Consent to 30 days after last dose ]
    Adverse events as measured by CTCAE version 5.0
  • Abnormal Laboratory Test results [ Time Frame: Consent to 30 days after last dose ]
    Changes and trends in standard hematology and chemistry blood tests
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
  • Safety and tolerability [ Time Frame: First 28 days of dosing ]
    Incidence of Dose Limiting Toxicities (DLT)
  • Safety and tolerability [ Time Frame: Consent to 30 days after last dose ]
    Incidence of adverse events (AE)
  • Safety and tolerability [ Time Frame: Consent to 30 days after last dose ]
    Changes and trends in standard hematology and chemistry blood tests
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
  • Establish the recommended phase 2 dose (RP2D) [ Time Frame: First 28 day cycle ]
    Incidence of DLTs
  • Pharmacokinetics of ON 123300 and 2 metabolites - Cmax [ Time Frame: 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) ]
    Maximum plasma concentration
  • Pharmacokinetics of ON 123300 and 2 metabolites - Tmax [ Time Frame: 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) ]
    Time to reach Cmax
  • Pharmacokinetics of ON 123300 and 2 metabolites - AUClast [ Time Frame: 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) ]
    The area under the plasma concentration-time curve (AUC) calculated to the last quantifiable sample
  • Pharmacokinetics of ON 123300 and 2 metabolites - T1/2 [ Time Frame: 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) ]
    Terminal phase elimination half-life
  • Pharmacokinetics of ON 123300 and 2 metabolites - CL/F [ Time Frame: 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) ]
    The apparent oral clearance
  • Pharmacokinetics of ON 123300 and 2 metabolites - Vss [ Time Frame: 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) ]
    Steady state volume of distribution
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 2, 2021)
Preliminary efficacy of ON 123300 [ Time Frame: Through study completion, an average of 6 months ]
Objective responses by RECIST
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of ON 123300 in Patients With Advanced Cancer
Official Title  ICMJE Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of ON 123300 Capsules Administered Orally as Escalating Daily Doses in Patients With Advanced Cancer Relapsed or Refractory to at Least One (1) Prior Line of Therapy
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.
Detailed Description

After being informed about the study including potential risks, patients giving written informed consent will proceed to a screening period when assessments will be performed to determine whether the patient is eligible to participate in the study. If the patient is eligible, they will start to receive ON 123300 as capsules every day. On day 1 and Day 8 of the study, patients will be required to provide eight blood samples to allow measurement of the amount of drug in their blood. Three ECGs will also be performed during this time. Patients will continue to receive ON 123300 until disease progression, unacceptable toxicity, or patient or physician decision to stop.

The first group of patients will receive 40mg of ON 123300 daily, the next group 80mg of ON 123300, the 120mg, etc. until the correct dose has been determined for future studies.

Patients will visit the clinic on Days 1, 2, 8, and 9, then weekly for the first month, then every two weeks for two more months, then every month.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
3+3 dose escalation design with expansion cohort at recommended phase 2 dose
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors, Adult
Intervention  ICMJE Drug: ON123300
ON 123300 hard gelatin capsules
Other Name: HX 301
Study Arms  ICMJE Experimental: ON 123300
ON 123300 capsules at increasing doses per cohort, starting at 40 mg
Intervention: Drug: ON123300
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 2, 2021)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2023
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. ≥ 18 years of age the time of signing the informed consent form (ICF);
  2. Histological or cytological evidence of advanced and/or metastatic cancer,

    1. For Dose Escalation Cohorts, patients with measurable or non-measurable disease;
    2. For RP2D Expansion Cohort, patients with measurable disease;
  3. 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;
  4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of < 2;
  5. Life expectancy of > 3 months;
  6. Patients must be able to swallow oral capsules;
  7. 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.
  8. Patients must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted;
  9. 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.
  10. 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;
  11. 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.

Exclusion Criteria:

  1. 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;
  2. Patients at risk for Torsades de pointes (TdP):

    1. 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
    2. who have a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or
    3. who are currently taking medications that prolong the QT/QTc interval;
  3. Patients with a diagnosis of hematological malignancies except for non-Hodgkin's lymphoma;
  4. Have received recent chemotherapy, hormonal therapy, other targeted cancer treatment, or investigational therapy within 14 days of planned first dose;
  5. Patients currently taking or within 5 half-lives of taking strong inducers and inhibitors of CYP2C8 and CYP3A4;
  6. History of allergic reaction attributed to compounds of similar chemical or biologic composition/structure to ON 123300 (e.g. prior CDK4/6 inhibitors);
  7. 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;
  8. Patients with a recent history of venous thromboembolic events, defined as event occurring ≤ 6 months prior to screening and also currently on therapy;
  9. Patients with baseline Grade ≥ 2 diarrhea;
  10. Patients with Grade ≥ 3 hypercalcemia (Corrected serum calcium > 12.5 mg/dL);
  11. Pregnant or nursing mothers;
  12. Have had major surgery within 14 days prior to screening to allow for post-operative healing of the surgical wound and site(s).
  13. Have received recent (within 28 days prior to screening) live attenuated vaccines.
  14. Have active bacterial, fungal or detectable viral infection (e.g. Human Immunodeficiency Virus or Hepatitis B or Hepatitis C).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04739293
Other Study ID Numbers  ICMJE 19-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Onconova Therapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Onconova Therapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michael E Saunders, MD Onconova Therapeutics
PRS Account Onconova Therapeutics, Inc.
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP