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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05355298




Registration number
NCT05355298
Ethics application status
Date submitted
7/04/2022
Date registered
2/05/2022
Date last updated
6/03/2024

Titles & IDs
Public title
ACCENT: AMP945 in Combination With Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic Cancer
Scientific 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
Secondary ID [1] 0 0
AMP945-PC-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Cancer 0 0
PDAC 0 0
Pancreatic Ductal Adenocarcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMP945 ascending doses
Treatment: Drugs - AMP945 RP2D

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


Treatment: Drugs: 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.

Treatment: Drugs: AMP945 RP2D
Part B will determine the efficacy of the AMP945 priming regimen at the recommended phase 2 dose (RP2D) determined in Part A.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study
Timepoint [1] 0 0
From first dose of study drug to end of study, an expected average of 6 months
Primary outcome [2] 0 0
Part A: Determination of RP2D
Timepoint [2] 0 0
After Cycle 1 (28 days) for each Part A cohort
Primary outcome [3] 0 0
Part B: efficacy of AMP945
Timepoint [3] 0 0
Imaging every 56 days per participant, with an expected average duration of 6 months
Secondary outcome [1] 0 0
Part A: efficacy of AMP945
Timepoint [1] 0 0
Imaging every 56 days per participant, with an expected average duration of 6 months
Secondary outcome [2] 0 0
AMP945 levels in plasma
Timepoint [2] 0 0
Days -8, -7, 1, 3, 4, 8 and 10
Secondary outcome [3] 0 0
AMP945 levels in plasma
Timepoint [3] 0 0
Days -8, -7, 1, 3, 4, 8 and 10
Secondary outcome [4] 0 0
AMP945 levels in plasma
Timepoint [4] 0 0
Days -8, -7, 1, 3, 4, 8 and 10

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2025
Actual
Sample size
Target
62
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
GenesisCare - St Leonards
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Gallipolli Medical Research Foundation - Greenslopes
Recruitment hospital [4] 0 0
Epworth Healthcare - Box Hill
Recruitment hospital [5] 0 0
Monash Health - Clayton
Recruitment hospital [6] 0 0
Epworth Healthcare - Richmond
Recruitment hospital [7] 0 0
Western Health - St Albans
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4120 - Greenslopes
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3121 - Richmond
Recruitment postcode(s) [7] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
Korea, Republic of
State/province [1] 0 0
Gyeonggi-do
Country [2] 0 0
Korea, Republic of
State/province [2] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amplia Therapeutics Limited
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05355298
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Information
Address 0 0
Country 0 0
Phone 0 0
+61 3 9123 1140
Fax 0 0
Email 0 0
info@ampliatx.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05355298