Trial Title:
A Study Evaluating the Safety, Pharmacokinetics and Early Efficacy of AVA6000 in Solid Tumours
NCT ID:
NCT04969835
Condition:
Pancreatic Cancer
Colorectal Cancer
Non-small Cell Lung Cancer
Head and Neck Cancer
Cancer of Unknown Primary Site
Ovarian Cancer
Breast Cancer
Soft Tissue Sarcoma
Bladder Cancer
Oesophageal Cancer
Prostate Cancer
Biliary Tract Cancer
Conditions: Official terms:
Sarcoma
Biliary Tract Neoplasms
Neoplasms, Unknown Primary
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
This Phase I study will follow a standard 3+3 design in Part 1a to determine the maximum
tolerated dose (MTD) and/or recommended dose of AVA6000, given as an intravenous
infusion, to be used in Part 1b in the dose-expansion phase in up to 3 tumour types.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AVA6000
Description:
AVA6000 is a FAP-activated prodrug of doxorubicin. AVA6000 will be administered via IV
infusion every 3 weeks. Dosing will occur based on the calculated patient's BSA on the
day of dosing.
Arm group label:
AVA6000 Phase 1a
Arm group label:
AVA6000 Phase 1b
Summary:
This open-label, First-into-Human (FIH) study will evaluate the safety, tolerability,
pharmacokinetics (PK) and early efficacy of AVA6000, a FAP-activated pro-drug of
doxorubicin, in patients with locally advanced and/or metastatic solid tumours. In Phase
Ia, using a 3+3 design, escalating doses of AVA6000 will be administered to patients with
a range of solid tumour types to determine the maximum tolerated dose (MTD) and/or
recommended Phase II dose (RP2D). In Phase 1b, the selected RP2D dose will be assessed in
one to three tumour types.
Detailed description:
This study is a first-in-human (FIH), Phase 1, open-label, multicentre, dose-escalation
study investigating AVA6000 monotherapy administered intravenously (IV) in patients with
locally advanced (unresectable) and/or metastatic solid tumours.
The study will be conducted in two parts: Phase 1a (Dose Escalation) and Phase 1b (Dose
Expansion):
Phase 1a (Dose Escalation): The dose-escalation phase is designed to evaluate the safety,
tolerability and MTD and/or RP2D of AVA6000, administered as monotherapy
Phase 1b (Dose Expansion): The dose-expansion phase will comprise 1 to 3 expansion arms
in specific tumour types to evaluate the safety and tolerability of AVA6000 at the MTD or
RP2D when administered as monotherapy. The tumour types to be explored in Phase 1b, will
be determined based on evaluation of the Phase 1a data and the protocol will be amended
accordingly.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
1. Willing and able to give written informed consent
2. Male or female patients, ≥18 years of age
3. Histological or cytological confirmation of a locally advanced (unresectable) and/or
metastatic pancreatic (PDAC), CRC, NSCLC, HNSCC, CUP, ovarian, breast, soft tissue
sarcoma, bladder, oesophageal, prostate, and biliary tract cancer, who have either
relapsed or progressed on SoC treatment or are intolerant or nonamenable to SoC
treatment
4. In Phase 1b part of the study only: At least 1 lesion, not previously irradiated,
that can be accurately measured at baseline as ≥10mm in the largest diameter (except
lymph nodes, which must have a short axis ≥15 mm) with CT or MRI scan and that is
suitable for accurate repeated measurements.
5. Life expectancy of greater than 12 weeks, in the opinion of the investigator
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
7. Recovered from all acute toxic effects of any prior radiotherapy, chemotherapy, or
surgical procedure (must have resolved to CTCAE grade ≤1 or returned to baseline,
except alopecia and peripheral neuropathy, which can be up to CTCAE grade 2)
8. Adequate haematological function (applies only to patients not receiving therapeutic
anticoagulation; patients receiving therapeutic anticoagulation should be on a
stable dose):
1. Neutrophil count of ≥1.5× 10^9 cells/L
2. Haemoglobin ≥9g/dL (with or without transfusion support)
3. Platelet count of ≥75,000/μL (without transfusion within 2 weeks prior to Cycle
1, Day 1)
4. International normalised ratio (INR) and activated partial thromboplastin time
(aPTT) ≤1.5 times the upper limit of normal (ULN)
9. Adequate liver function:
1. Total bilirubin ≤1.5 × ULN (in patients with Gilbert's Syndrome, <3 × ULN is
allowed)
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN
(in patients with liver metastases, <5 × ULN is allowed)
3. Alkaline phosphatase (ALP) <5 × ULN (patients with documented liver or bone
metastases only)
10. Adequate renal function:
a. Serum creatinine ≤1.5 × ULN (in patients for whom, in the Investigator's
judgment, serum creatinine levels do not adequately reflect renal function,
creatinine clearance by Cockcroft-Gale formula ≥ 50 mL/min may be used)
11. Women of childbearing potential (WOCBP) and women who have ≤ 2 years amenorrhea
after start of menopause: has a negative serum pregnancy test within 7 days prior to
Cycle 1, Day 1
12. Contraception requirements:
1. Female patients of childbearing potential must agree to remain abstinent
(refrain from heterosexual intercourse) or use a highly effective contraceptive
method (Pearl Index failure rate <1% per year) during the treatment period and
for at least 6 months after the last dose of study drug
2. Male patients with female partners of childbearing potential must agree to use
2 acceptable methods of contraception (Pearl Index failure rate <1% per year),
including a barrier method (with or without spermicide) during the treatment
period and for at least 6 months after the last dose of study drug
Key Exclusion Criteria:
1. Received trastuzumab within 7 months of the planned Cycle 1, Day 1 AVA6000 infusion
2. Received a prior total cumulative anthracycline dose of >350mg/m^2 doxorubicin
hydrochloride (or equivalent anthracycline dose)
3. Clinically significant or untreated central nervous system (CNS) metastases
requiring treatment, as determined by the Investigator.
4. Has leptomeningeal disease
5. Any history of an active (requiring treatment) other malignancy (except any in-situ
carcinoma, non-melanoma skin carcinoma and early prostate cancer with a normal PSA)
within 2 years of study entry
6. Has a significant, uncontrolled, concomitant disease that could affect compliance
with the protocol
7. Has uncontrolled hypertension (systolic blood pressure [SBP] >150 mmHg and/or
diastolic [DBP] >100 mm Hg), unstable angina, congestive heart failure (New York
Heart Association (NYHA) Class >II), left ventricular ejection fraction (LVEF) <55%
or the low limit of institutional normal limit (whichever is lower) by
echocardiogram (ECHO), serious cardiac arrhythmia requiring treatment (exceptions
include atrial fibrillation, paroxysmal supraventricular tachycardia), history of
myocardial infarction within 6 months prior to Cycle 1, Day 1; history of
uncontrolled cardiovascular disease or high-sensitivity troponin above normal at
baseline
8. Screening baseline mean QTcF interval (Fridericia's) of >470 msec, obtained from 3
electrocardiograms (ECGs). Has any clinically significant abnormalities in rhythm,
conduction, or morphology of resting ECG (e.g., complete left bundle branch block,
third-degree heart block, second-degree heart block, PR interval >250msec). Has any
factors that increase the risk of QTc prolongation or risk of arrhythmic events such
as heart failure, hypokalaemia, congenital long QT syndrome, known family history of
long QT syndrome or unexplained sudden death under 40 years of age in first degree
relatives or any concomitant medication known to prolong the QT interval, a baseline
resting bradycardia <45 beats/min or a baseline resting tachycardia of >100
beats/min
9. Known uncontrolled HIV infection
10. Active hepatitis B (HBV) or hepatitis C (HCV) infection:
1. Positive hepatitis B surface antigen (HBsAG) test at Screening. Patients with a
past or resolved HBV infection (defined as having a negative HBsAG test and a
positive antibody to hepatitis B core antigen [antiHBc] antibody test) are
eligible.
2. Patients positive for HCV antibody are eligible only if PCR is negative for HCV
RNA
11. Severe infection(requiring IV treatment)within 21 days prior to Cycle 1, Day 1
including, but not limited to, hospitalisation for complications of infection,
bacteraemia, or severe pneumonia
12. Any other clinically significant active disease, metabolic dysfunction, physical
examination finding, clinical laboratory finding, or reasonable suspicion of a
disease or condition that would contraindicate the use of an investigational drugin
the opinion of the investigator.
13. Major surgery within 21 days prior to Cycle 1, Day 1 (excluding biopsies) or
anticipates the need for major surgery during study treatment
14. Has dementia or altered mental status that in the opinion of the investigator would
preclude providing informed consent
15. Pregnant or breastfeeding woman
16. Known hypersensitivity to any of the components of AVA6000 or any excipient related
to the product
17. Received prior investigational therapy (defined as a treatment for which there is no
Regulatory Authority-approved indication) within 21 or 42 days of Cycle 1 Day 1, for
small molecule and biologic investigational therapies, respectively.
18. Received any approved anticancer therapy, including chemotherapy or hormonal
therapy, within 28 days prior to Cycle 1, Day 1, with the following exceptions:
1. Hormone-replacement therapy or oral contraceptives
2. Tyrosine kinase inhibitors (TKIs) that have been discontinued more than 7 days
prior to Cycle1, Day 1
19. Is planned for on study treatment or has received within 21 days prior to Cycle 1,
Day 1: St John's Wort, any strong inhibitor or inducer of CYP3A4, CYP2D6, narrow
therapeutic index CYP1A2, CYP2B6, or P-glycoprotein (PGP) ̧ or any moderate OATP1B3
inhibitor (will include statins)
20. Received systemic immunosuppressive medication (for any indication) at doses of
>10mg prednisolone (or equivalent) within 28 days prior to Cycle 1, Day 1.
21. Received radiotherapy within 28 days prior to Cycle 1, Day 1, except for limited
field palliative radiotherapy. Patients who have received prior or concomitant
radiotherapy to the mediastinal area are also excluded.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Dr William Tap
Email:
Principal Investigator
Facility:
Name:
Fred Hutchinson Cancer Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Professor Lee Cranmer
Email:
Principal Investigator
Facility:
Name:
The Beatson West of Scotland Cancer Centre, NHS Greater Glasgow & Clyde
Address:
City:
Glasgow
Zip:
G12 0YN
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Professor Jeff Evans
Email:
Principal Investigator
Facility:
Name:
St James's University Hospital, The Leeds Teaching Hospitals NHS Trust
Address:
City:
Leeds
Zip:
LS9 7TF
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Professor Chris Twelves
Email:
Principal Investigator
Facility:
Name:
The Royal Marsden, NHS Foundation Trust
Address:
City:
London
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Professor Udai Banerji
Email:
Principal Investigator
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Dr Natalie Cook
Email:
Principal Investigator
Facility:
Name:
The Freeman Hospital, Newcastle-upon-Tyne NHS Foundation Trust
Address:
City:
Newcastle upon Tyne
Zip:
NE7 7DN
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Professor Ruth Plummer
Email:
Principal Investigator
Facility:
Name:
Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust
Address:
City:
Sheffield
Zip:
S10 2SJ
Country:
United Kingdom
Status:
Not yet recruiting
Investigator:
Last name:
Dr Robin Young
Email:
Principal Investigator
Start date:
July 16, 2021
Completion date:
June 30, 2023
Lead sponsor:
Agency:
Avacta Life Sciences Ltd
Agency class:
Industry
Source:
Avacta Life Sciences Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT04969835
