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Trial record 1 of 1 for:    NCT03520075
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Study of ASTX029 in Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03520075
Recruitment Status : Recruiting
First Posted : May 9, 2018
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE April 18, 2018
First Posted Date  ICMJE May 9, 2018
Last Update Posted Date July 8, 2020
Actual Study Start Date  ICMJE May 10, 2018
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2018)
  • Safety (Phase 1) - Dose-limiting toxicities including incidence of Treatment-Emergent Adverse Events [ Time Frame: End of each dosing cycle (Day 21 of 21-day cycle) ]
    Number of subjects with dose-limiting toxicities
  • Efficacy (Phase 2) - Response Evaluation Criteria in Solid Tumors using RECIST v1.1 [ Time Frame: Baseline to measured progressive disease or start of new anticancer therapy, through study completion, an average of 6 months to 1 year ]
    Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2018)
  • Pharmacokinetic profile of ASTX029 - AUC [ Time Frame: Day 1 and 2 of Cycle 1 and Cycle 2 for Regimen 1, and Day 1, 2, 14, and 15 of Cycle 1 for Regimen 2 ]
    1) Area under the time-concentration curve
  • Pharmacokinetic profile of ASTX029 - Cmax [ Time Frame: Day 1 and 2 of Cycle 1 and Cycle 2 for Regimen 1, and Day 1, 2, 14, and 15 of Cycle 1 for Regimen 2 ]
    2) Maximum plasma concentration
  • Pharmacokinetic profile of ASTX029 - Cmin [ Time Frame: Day 1 and 2 of Cycle 1 and Cycle 2 for Regimen 1, and Day 1, 2, 14, and 15 of Cycle 1 for Regimen 2 ]
    3) Minimum plasma concentration
  • Pharmacokinetic profile of ASTX029 - Tmax [ Time Frame: Day 1 and 2 of Cycle 1 and Cycle 2 for Regimen 1, and Day 1, 2, 14, and 15 of Cycle 1 for Regimen 2 ]
    4) Time to reach maximum concentration
  • Pharmacokinetic profile of ASTX029 - Half-life [ Time Frame: Day 1 and 2 of Cycle 1 and Cycle 2 for Regimen 1, and Day 1, 2, 14, and 15 of Cycle 1 for Regimen 2 ]
    5) Elimination half-life
  • Pharmacokinetic profile of ASTX029 - Metabolites [ Time Frame: Day 1 and 2 of Cycle 1 and Cycle 2 for Regimen 1, and Day 1, 2, 14, and 15 of Cycle 1 for Regimen 2 ]
    6) Analysis of ASTX029 metabolites if applicable
  • Efficacy - DOR [ Time Frame: Baseline to measured progressive disease or start of new anticancer therapy, through study completion, an average of 6 months to 1 year ]
    Duration of response
  • Efficacy - DCR [ Time Frame: Baseline to measured progressive disease or start of new anticancer therapy, through study completion, an average of 6 months to 1 year ]
    Disease control rate
  • Efficacy - PFS [ Time Frame: Baseline to measured progressive disease or start of new anticancer therapy, through study completion, an average of 6 months to 1 year ]
    Progressive-free survival
  • Efficacy - OS [ Time Frame: Baseline to measured progressive disease or start of new anticancer therapy, through study completion, an average of 6 months to 1 year ]
    Overall survival
  • Target engagement in tumor tissues - pRSK [ Time Frame: Day 8 of Cycle 2 ]
    Inhibition of phosphorylated ribosomal s6 kinase protein in response to ASTX029 treatment in fresh tumor biopsies
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ASTX029 in Subjects With Advanced Solid Tumors
Official Title  ICMJE A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects With Advanced Solid Tumors
Brief Summary This study is a first-in-human, open-label, multicenter, Phase 1-2 study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of ASTX029 administered orally to subjects with advanced solid malignancies who are not candidates for approved or available therapies.
Detailed Description ASTX029 is a synthetic small molecule inhibitor of extracellular signal-regulated kinases (ERKs) 1/2. ASTX029 has not been previously evaluated in human subjects. The Phase 1 portion of this study will assess safety and determine the maximum tolerated dose, the recommended Phase 2 dose (RP2D), and the recommended dosing regimen of ASTX029 administered orally. The Phase 2 portion will assess preliminary clinical activity in tumors characterized by gene aberrations in the mitogen-activated protein kinase (MAPK) signal pathway that may confer sensitivity to ASTX029.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor, Adult
Intervention  ICMJE Drug: ASTX029
Described above
Study Arms  ICMJE
  • Experimental: Phase 1 Regimen 1

    Dose escalation and expansion:

    Regimen 1: ASTX029 orally once a day for 21 days of each 21-day cycle.

    Intervention: Drug: ASTX029
  • Experimental: Phase 1 Regimen 2

    Dose escalation and expansion:

    Regimen 2: ASTX029 orally once a day for 14 days of each 21-day cycle.

    Intervention: Drug: ASTX029
  • Experimental: Phase 2
    ASTX029 at the RP2D of the selected dosing regimen identified in Phase 1 to subjects with tumors characterized by gene aberrations in the MAPK signal pathway that may confer sensitivity to ASTX029.
    Intervention: Drug: ASTX029
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: May 8, 2018)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 14, 2022
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Subjects must fulfill all of the following inclusion criteria.

  1. Able to understand and comply with study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
  2. Men or women 18 years of age or older.
  3. Subjects with histologically or cytologically confirmed advanced solid tumors that are metastatic or unresectable, who are refractory or have relapsed after treatment with available therapies or for whom standard life-prolonging measures or approved therapies are not available. In Phase 1 Part B (except in the potential food-effect cohort) and in the Phase 2 portion of the protocol, subjects must also have documented gene alterations in the MAPK pathway as detailed in the protocol.
  4. In Phase 1 Part B (except in the potential food-effect cohort) of the protocol, subjects must have disease lesions that are amenable to biopsy.
  5. In the Phase 2 portion of the protocol, subjects must have measurable disease according to RECIST v1.1.
  6. Eastern Cooperative Oncology Group performance status 0 to 2.
  7. Acceptable organ function as evidenced by the following laboratory data:

    1. Aspartate aminotransferase and alanine aminotransferase ≤2×upper limit of normal (ULN) or ≤3 ULN in the presence of liver metastases.
    2. Total serum bilirubin ≤1.5×ULN.
    3. Absolute neutrophil count ≥1500 cells/mm3.
    4. Platelet count ≥100,000 cells/mm3.
    5. Calculated creatinine clearance (by the standard Cockcroft Gault formula) of ≥50 mL/min or glomerular filtration rate of ≥50 mL/min.
  8. Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group as detailed in the protocol) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures (as described in the protocol) during the study and for at least 3 months after completing treatment and must agree not to become pregnant or father a child while receiving study treatment and for at least 3 months after completing treatment.

Exclusion Criteria:

  1. Hypersensitivity to ASTX029 or excipients of the drug product.
  2. Poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
  3. Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise subject safety or the integrity of study outcomes or interfere with the absorption or metabolism of ASTX029.
  4. Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX029), as follows:

    1. Cytotoxic chemotherapy or radiotherapy within 3 weeks prior and any encountered treatment-related toxicities (excepting alopecia) not stabilized or resolved to ≤Grade 1.
    2. Monoclonal antibodies within 4 weeks prior and any encountered treatment-related toxicities not resolved to ≤Grade 1.
    3. Molecularly targeted drug or investigational drugs, without the potential for delayed toxicity, within 4 weeks of the first dose of study treatment or 5 half-lives (minimum 14 days), whichever is shorter.
  5. Prior treatment with ERK inhibitors.
  6. History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:

    1. Abnormal left ventricular ejection fraction (<50%) on echocardiogram or multiple-gated acquisition scan.
    2. Congestive cardiac failure of ≥Grade 3 severity according to New York Heart Association functional classification defined as patients with marked limitation of activity and who are comfortable only at rest.
    3. Unstable cardiac disease including unstable angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
    4. History or evidence of long QT interval corrected for heart rate (QTc), ventricular arrhythmias including ventricular bigeminy, complete left bundle branch block, clinically significant bradyarrhythmias such as sick sinus syndrome, second- and third-degree atrioventricular block, presence of cardiac pacemaker or defibrillator, or other significant arrhythmias.
    5. Screening 12-lead electrocardiogram with measurable QTc interval of ≥470 msec. (Fridericia's formula should be used to calculate the QTc interval throughout the study.)
  7. Known history of human immunodeficiency virus infection or seropositive results consistent with active hepatitis B virus or active hepatitis C virus infection.
  8. Known brain metastases, unless previously treated and stable for at least 3 months with or without steroids.
  9. Known significant mental illness or other conditions, such as active alcohol or other substance abuse that, in the opinion of the investigator, predispose the subject to high risk of noncompliance with the protocol treatment or assessments.
  10. History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:

    1. Presence of predisposing factors to RVO or CSR (eg, uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus) or
    2. Visible retinal pathology as assessed by ophthalmic examination at screening that is considered a risk factor for RVO or CSR such as:

      • Evidence of optic disc cupping or
      • Evidence of new visual field defects on automated perimetry or
      • Intraocular pressure >21 mmHg as measured by tonography.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Richard J Morishige, MS, RRT, RAC +1 925-560-2882 Richard.Morishige@astx.com
Contact: Shwetha Sanga +1 925- 560-2931 Shwetha.Sanga@astx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03520075
Other Study ID Numbers  ICMJE ASTX029-01
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 Not Provided
Responsible Party Astex Pharmaceuticals, Inc.
Study Sponsor  ICMJE Astex Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kim-Hien Dao, DO, PhD Astex Pharmaceuticals, Inc.
PRS Account Astex Pharmaceuticals, Inc.
Verification Date July 2020

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