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AMP945 in Combination With Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic Cancer

Primary Purpose

Pancreatic Cancer, PDAC, Pancreatic Ductal Adenocarcinoma

Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
AMP945 ascending doses
AMP945 RP2D
Sponsored by
Amplia Therapeutics Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • GenesisCareRecruiting
  • Westmead HospitalRecruiting
  • Gallipolli Medical Research FoundationRecruiting
  • Epworth HealthcareRecruiting
  • Monash HealthRecruiting
  • Epworth HealthcareRecruiting
  • Western HealthRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AMP945

Arm Description

Part A: AMP945 administered in dose escalating cohorts Part B: AMP945 recommended phase 2 dose

Outcomes

Primary Outcome Measures

Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study
TEAEs during study treatment and follow up periods
Part A: Determination of RP2D
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
Overall response rate based on RECIST 1.1

Secondary Outcome Measures

Part A: efficacy of AMP945
Overall response rate based on RECIST 1.1
AMP945 levels in plasma
Measurement of maximum concentration (cmax) of AMP945
AMP945 levels in plasma
Measurement of time to cmax (tmax)
AMP945 levels in plasma
Measurement of clearance (CL)

Full Information

First Posted
April 7, 2022
Last Updated
December 7, 2022
Sponsor
Amplia Therapeutics Limited
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1. Study Identification

Unique Protocol Identification Number
NCT05355298
Brief Title
AMP945 in Combination With Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 31, 2022 (Actual)
Primary Completion Date
May 1, 2025 (Anticipated)
Study Completion Date
May 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amplia Therapeutics Limited

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, PDAC, Pancreatic Ductal Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AMP945
Arm Type
Experimental
Arm Description
Part A: AMP945 administered in dose escalating cohorts Part B: AMP945 recommended phase 2 dose
Intervention Type
Drug
Intervention Name(s)
AMP945 ascending doses
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
AMP945 RP2D
Intervention Description
Part B will determine the efficacy of the AMP945 priming regimen at the recommended phase 2 dose (RP2D) determined in Part A.
Primary Outcome Measure Information:
Title
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study
Description
TEAEs during study treatment and follow up periods
Time Frame
From first dose of study drug to end of study, an expected average of 6 months
Title
Part A: Determination of RP2D
Description
The RP2D of AMP945 will be determined based on either the maximum tolerated dose or maximum pharmacodynamic effect, which ever is reached first
Time Frame
After Cycle 1 (28 days) for each Part A cohort
Title
Part B: efficacy of AMP945
Description
Overall response rate based on RECIST 1.1
Time Frame
Imaging every 56 days per participant, with an expected average duration of 6 months
Secondary Outcome Measure Information:
Title
Part A: efficacy of AMP945
Description
Overall response rate based on RECIST 1.1
Time Frame
Imaging every 56 days per participant, with an expected average duration of 6 months
Title
AMP945 levels in plasma
Description
Measurement of maximum concentration (cmax) of AMP945
Time Frame
Days -8, -7, 1, 3, 4, 8 and 10
Title
AMP945 levels in plasma
Description
Measurement of time to cmax (tmax)
Time Frame
Days -8, -7, 1, 3, 4, 8 and 10
Title
AMP945 levels in plasma
Description
Measurement of clearance (CL)
Time Frame
Days -8, -7, 1, 3, 4, 8 and 10
Other Pre-specified Outcome Measures:
Title
Overall response
Description
Overall response, based on RECIST, by imaging timepoint
Time Frame
Imaging every 56 days per participant, with an expected average duration of 6 months
Title
Duration of response (DOR)
Description
DOR based on RECIST defined as the time from the date of the first confirmed response to the date of progression or death
Time Frame
Imaging every 56 days per participant, with an expected average duration of 6 months
Title
Overall survival (OS)
Description
OS of participants, defined as time from first dose until death from any cause
Time Frame
Imaging every 56 days per participant, with an expected average duration of 6 months
Title
Progression free survival (PFS)
Description
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 Frame
Imaging every 56 days per participant, with an expected average duration of 6 months
Title
Time to progression
Description
Time to progression, defined as time from first dosing to date of first observed progression, based on RECIST
Time Frame
Imaging every 56 days per participant, with an expected average duration of 6 months
Title
Clinical benefit rate (CBR)
Description
CBR defined as complete response (CR) + partial response (PR) + stable disease
Time Frame
Imaging every 56 days per participant, with an expected average duration of 6 months
Title
Effects on tumor antigens
Description
Changes in levels of tumour antigens (serum CA19-9) at the end of each treatment cycle compared to baseline
Time Frame
Every 28 days per participant, with an expected average duration of 6 months
Title
Effects on biomarkers
Description
Change in levels of other relevant blood biomarkers including p-FAK, PRO-C3, PRO-C6, PRO-C11, C3M, C6M, and C4G
Time Frame
Every 28 days per participant, with an expected average duration of 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provide written informed consent prior to any study procedures and agree to adhere to all protocol requirements. Aged at least 18 years at the time of consent. 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. 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. Eligible for treatment with nab-paclitaxel and gemcitabine as standard of care therapy. 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. Has a life expectancy of >3 months. 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. Agree to use contraception according to protocol Exclusion Criteria: Pregnant or breast-feeding, or plans to become pregnant during the study. Has received any investigational medicinal product (IMP) within 30 days or 5 half-lives (whichever is longer) prior to Day -8. 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). Gastrointestinal condition that could interfere with the swallowing or absorption of study medication. 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. 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. History of malignancy other than in situ cancer or basal or squamous cell skin cancer in the last 5 years. 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. 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. Known history of myocardial infarction, coronary stenting, stroke, or cerebrovascular accident within 6 months prior to the first dose of study drug. 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. History of chronic leukemias (e.g., chronic lymphocytic leukemia). History of interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies. History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa). 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). Currently using warfarin. 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. 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. 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. Peripheral neuropathy > Grade 1. Corrected QT interval using Fridericia's correction (QTcF) > 460 ms for males and >480 ms for females. 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. Prior treatment with AMP945.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Information
Phone
+61 3 9123 1140
Email
info@ampliatx.com
Facility Information:
Facility Name
GenesisCare
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Email
referrals.northshore@genesiscare.com
Email
sydneynorthresearch@genesiscare.com
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Email
WSLHD-MOTU@health.nsw.gov.au
Facility Name
Gallipolli Medical Research Foundation
City
Greenslopes
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Email
enquiries.grf@ramsayhealth.com.au
Facility Name
Epworth Healthcare
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Email
EHjreissaticentre@epworth.org.au
Facility Name
Monash Health
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Email
gi.oncresearch@monashhealth.org
Facility Name
Epworth Healthcare
City
Richmond
State/Province
Victoria
ZIP/Postal Code
3121
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Email
EHjreissaticentre@epworth.org.au
Facility Name
Western Health
City
St Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
Email
CancerClinicalTrials@wh.org.au

12. IPD Sharing Statement

Plan to Share IPD
No

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AMP945 in Combination With Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic Cancer

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