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AMP945 in Combination With Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic 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: NCT05355298
Recruitment Status : Recruiting
First Posted : May 2, 2022
Last Update Posted : August 15, 2022
Sponsor:
Information provided by (Responsible Party):
Amplia Therapeutics Limited

Tracking Information
First Submitted Date  ICMJE April 7, 2022
First Posted Date  ICMJE May 2, 2022
Last Update Posted Date August 15, 2022
Actual Study Start Date  ICMJE May 31, 2022
Estimated Primary Completion Date May 1, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2022)
  • Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study [ Time Frame: From first dose of study drug to end of study, an expected average of 6 months ]
    TEAEs during study treatment and follow up periods
  • Part A: Determination of RP2D [ Time Frame: After Cycle 1 (28 days) for each Part A cohort ]
    The RP2D of AMP945 will be determined based on either the maximum tolerated dose or maximum pharmacodynamic effect, which ever is reached first
  • Part B: efficacy of AMP945 [ Time Frame: Imaging every 56 days per participant, with an expected average duration of 6 months ]
    Overall response rate based on RECIST 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2022)
  • Part A: efficacy of AMP945 [ Time Frame: Imaging every 56 days per participant, with an expected average duration of 6 months ]
    Overall response rate based on RECIST 1.1
  • AMP945 levels in plasma [ Time Frame: Days -8, -7, 1, 3, 4, 8 and 10 ]
    Measurement of maximum concentration (cmax) of AMP945
  • AMP945 levels in plasma [ Time Frame: Days -8, -7, 1, 3, 4, 8 and 10 ]
    Measurement of time to cmax (tmax)
  • AMP945 levels in plasma [ Time Frame: Days -8, -7, 1, 3, 4, 8 and 10 ]
    Measurement of clearance (CL)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 27, 2022)
  • Overall response [ Time Frame: Imaging every 56 days per participant, with an expected average duration of 6 months ]
    Overall response, based on RECIST, by imaging timepoint
  • Duration of response (DOR) [ Time Frame: Imaging every 56 days per participant, with an expected average duration of 6 months ]
    DOR based on RECIST defined as the time from the date of the first confirmed response to the date of progression or death
  • Overall survival (OS) [ Time Frame: Imaging every 56 days per participant, with an expected average duration of 6 months ]
    OS of participants, defined as time from first dose until death from any cause
  • Progression free survival (PFS) [ Time Frame: Imaging every 56 days per participant, with an expected average duration of 6 months ]
    PFS of participants, defined as time from first dose to date of first observed progression, based on RECIST, or death from any cause (whichever comes first)
  • Time to progression [ Time Frame: Imaging every 56 days per participant, with an expected average duration of 6 months ]
    Time to progression, defined as time from first dosing to date of first observed progression, based on RECIST
  • Clinical benefit rate (CBR) [ Time Frame: Imaging every 56 days per participant, with an expected average duration of 6 months ]
    CBR defined as complete response (CR) + partial response (PR) + stable disease
  • Effects on tumor antigens [ Time Frame: Every 28 days per participant, with an expected average duration of 6 months ]
    Changes in levels of tumour antigens (serum CA19-9) at the end of each treatment cycle compared to baseline
  • Effects on biomarkers [ Time Frame: Every 28 days per participant, with an expected average duration of 6 months ]
    Change in levels of other relevant blood biomarkers including p-FAK, PRO-C3, PRO-C6, PRO-C11, C3M, C6M, and C4G
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE AMP945 in Combination With Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic Cancer
Official Title  ICMJE A Phase 1b/2a, Multicentre, Open Label Study of the Pharmacokinetics, Safety and Efficacy of AMP945 in Combination With Nab-paclitaxel and Gemcitabine in Pancreatic Cancer Patients
Brief Summary

This is a multicentre, open label, two-part study to determine whether the focal adhesion kinase (FAK) inhibitor AMP945, when given prior to dosing with gemcitabine and nab-paclitaxel, improves response to therapy in first-line patients with unresectable or metastatic pancreatic cancer.

Part A is a phase 1b dose-escalation design that will enrol at least 3 participants in each of 4 dose-level cohorts, to determine the RP2D of AMP945 to be explored in Part B.

Part B will determine the efficacy of the AMP945 regimen at the RP2D, and will be run as a Simon Two-stage design; Stage 1 will enrol 26 participants. If ≤5 of the 26 participants show an objective response, then recruitment will be paused and a detailed analysis of futility will be performed. If the study is deemed futile, recruitment will cease. If the study is determined to be not futile or >5 of the 26 participants show an objective response, recruitment will continue, and an additional 24 participants will be enrolled in Stage 2.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Single arm study but 2 parts;

  • Part A is dose escalation
  • Part B is open label single dose level
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pancreatic Cancer
  • PDAC
  • Pancreatic Ductal Adenocarcinoma
Intervention  ICMJE
  • Drug: AMP945 ascending doses
    Part A is a phase 1b dose-escalation design that will enrol at least 3 participants in each of 4 dose-level cohorts, to determine the RP2D of AMP945 to be explored in Part B. Dose escalation decisions will be made using a standard 3+3 dose-escalation phase 1 oncology study design.
  • Drug: AMP945 RP2D
    Part B will determine the efficacy of the AMP945 priming regimen at the recommended phase 2 dose (RP2D) determined in Part A.
Study Arms  ICMJE Experimental: AMP945
Part A: AMP945 administered in dose escalating cohorts Part B: AMP945 recommended phase 2 dose
Interventions:
  • Drug: AMP945 ascending doses
  • Drug: AMP945 RP2D
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: April 27, 2022)
62
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2025
Estimated Primary Completion Date May 1, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provide written informed consent prior to any study procedures and agree to adhere to all protocol requirements.
  2. Aged at least 18 years at the time of consent.
  3. Confirmed histological or cytological diagnosis of advanced pancreatic adenocarcinoma that is:

    Part A: metastatic or not surgically resectable.

    Part B: metastatic, with initial diagnosis of metastatic disease ≤6 weeks prior to Baseline.

  4. Has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
  5. Eligible for treatment with nab-paclitaxel and gemcitabine as standard of care therapy.
  6. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1, sustained on two separate assessments: the first at least 2 weeks prior to the 1st dose of AMP945 and the 2nd within 72 hours prior to the 1st dose of AMP945. Participants not maintaining an ECOG Performance Score of 0-1 at the second assessment will be excluded from participation.
  7. Has a life expectancy of >3 months.
  8. Adequate organ function, as defined by the laboratory results below (samples must be obtained ≤14 days prior to study drug administration):

    a) Haematology:

    (i) Absolute neutrophil count (ANC) ≥1.5 × 109/L;

    (ii) Platelet count ≥100,000/mm3 (100 × 109/L);

    (iii) Haemoglobin (Hgb) ≥9 g/dL.

    b) Serum chemistry:

    (i) Aspartate transaminase (AST) (SGOT), ALT (SGPT) ≤2.5 × upper limit of normal range (ULN), unless liver metastases are clearly present, then ≤5 × ULN is allowed;

    (ii) Total bilirubin ≤ULN;

    (iii) Creatinine <1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR) >60 mL/min/1.73m2 (calculated using the Cockcroft-Gault equation).

    c) No clinically significant abnormalities in coagulation results.

    d) No clinically significant abnormalities in urinalysis results.

  9. Agree to use contraception according to protocol

Exclusion Criteria:

  1. Pregnant or breast-feeding, or plans to become pregnant during the study.
  2. Has received any investigational medicinal product (IMP) within 30 days or 5 half-lives (whichever is longer) prior to Day -8.
  3. Known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no oedema, no steroids and stable in 2 scans at least 4 weeks apart).
  4. Gastrointestinal condition that could interfere with the swallowing or absorption of study medication.
  5. Part A: Has received prior systemic treatments for pancreatic cancer, except those given in the adjuvant setting, and with recurrence more than 6 months after completion of curative/adjuvant treatment.
  6. Part B: Has received no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Participants having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study.
  7. History of malignancy other than in situ cancer or basal or squamous cell skin cancer in the last 5 years.
  8. Major surgery, other than diagnostic surgery (i.e., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day -8.
  9. Known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections or known to be positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C Antibody.
  10. Known history of myocardial infarction, coronary stenting, stroke, or cerebrovascular accident within 6 months prior to the first dose of study drug.
  11. Focal palliative radiotherapy (e.g., to a bony metastasis) within the 14 days prior to Run-in, or more extensive radiotherapy within 28 days prior to Run-in.
  12. History of chronic leukemias (e.g., chronic lymphocytic leukemia).
  13. History of interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
  14. History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).
  15. Clinical signs of active infection and/or a temperature of > 38.0°C at the time of Screening or Baseline. Study entry may be deferred at the discretion of the Principal Investigator (PI).
  16. Currently using warfarin.
  17. Administration of a live virus vaccine in the 4 weeks prior to Day -8 or plans to receive a live virus vaccine during the study.
  18. Clinically significant allergies to AMP945, nab-paclitaxel or gemcitabine (or any of their excipients), including hypersensitivity reactions to human albumin, that are not likely to be well controlled with premedication or other supportive measures.
  19. Exhibiting any of the conditions or events outlined in the Contraindications or Special Warnings and Precautions sections of the nab-paclitaxel and/or gemcitabine package inserts.
  20. Peripheral neuropathy > Grade 1.
  21. Corrected QT interval using Fridericia's correction (QTcF) > 460 ms for males and >480 ms for females.
  22. Any clinically relevant medical, social, or psychiatric conditions, or any finding during Screening, which in the Investigator's opinion may put the participant at unacceptable risk or interfere with the study objectives.
  23. Prior treatment with AMP945.
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: John Lambert +61409525259 info@ampliatx.com
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05355298
Other Study ID Numbers  ICMJE AMP945-PC-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Amplia Therapeutics Limited
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Amplia Therapeutics Limited
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Amplia Therapeutics Limited
Verification Date August 2022

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