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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02999893




Registration number
NCT02999893
Ethics application status
Date submitted
5/12/2016
Date registered
21/12/2016
Date last updated
9/08/2019

Titles & IDs
Public title
A Study of APR-246 in Oesophageal Cancer
Scientific title
A phase1b/2 Study Evaluating the Efficacy of APR-246, a First-in-class Agent Targeting Mutant p53 in the Treatment of Platinum Resistant Advanced and Metastatic Oesophageal or Gastro-oesophageal Junction Cancers
Secondary ID [1] 0 0
16/012
Universal Trial Number (UTN)
Trial acronym
APROC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Oesophageal Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APR-246

Experimental: APR-246 - The trial regimen consists of the investigational agent APR-246, along with standard chemotherapy, Cisplatin and 5-FU. A maximum of 8 cycles of treatment will be given.
APR-246 and 5-FU must both commence on Day 1 and given on days 1 to 4 via intravenous infusion over 6 hours, whilst 5-FU must be given as a continuous infusion over 96 hours.
On Days 2-4, APR-246 must be given first via intravenous infusion over 6 hours, then commence cisplatin via intravenous infusion over one hour.
This is a dose-escalation study to determine the maximum tolerated dose (MTD) of the combination therapy. The 3 dose levels are described as follows:
Dose Level 1:
APR-246 Dose: 75mg/kg LBM Cisplatin Dose: 25mg/m2 5-FU Dose: 750mg/m2/ day CI
Dose Level 2:
APR-246 Dose: 100mg/kg LBM Cisplatin Dose: 25mg/m2 5-FU Dose: 750mg/m2/ day CI
Dose Level -1:
APR-246 Dose: 50mg/kg LBM Cisplatin Dose: 25mg/m2 5-FU Dose: 750mg/m2/ day CI


Treatment: Drugs: APR-246
APR-246 (also known as PRIMA-1MET), a first-in-class agent targeting mutant p53 resulting in re-expression of wild-type p53 activity.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Establish the safety profile of combined APR-246 plus cisplatin and 5FU as measured by the satisfactorily low rate of adverse events described according to NCI CTCAE v 4.03.
Timepoint [1] 0 0
3 weeks post commencement of treatment.
Secondary outcome [1] 0 0
Evidence of clinical efficacy of a combined APR-246 and cisplatin/5FU chemotherapy regimen as confirmed by CT/PET/MRI scan.
Timepoint [1] 0 0
6 and 12 weeks post commencement of treatment.

Eligibility
Key inclusion criteria
1. Male or female aged 18 years or older at screening

2. Histologically-confirmed metastatic or advanced oesophageal or oesophago-gastric
junction adenocarcinoma or squamous cell carcinoma

3. Radiologic disease progression at or within 6 months of platinum containing
chemotherapy in the advanced/metastatic or adjuvant setting

4. Measurable disease as per RECIST1.1 criteria

5. Measurable lesions must not have previously had radiotherapy or must have progressed
following radiotherapy

6. Patients may have had up to 2 lines of previous chemotherapy in the
metastatic/advanced setting or 3 lines including adjuvant therapy. If patients have a
maintenance strategy following platinum containing chemotherapy (e.g. fluoropyrimidine
alone) this will not be considered a separate line of treatment.

7. Patient has provided written informed consent for the trial

8. Tumour tissue available from the initial surgical resection or any previous biopsies
taken at any time before screening. Either a FFPE block or 15 unstained sections from
the tumour tissue block must be available for the purpose of translation research
studies. Obtaining archived tumour material or unstained sections from an archived
tumour block will suffice to meet this requirement. The availability of the tumour
material must be confirmed at Screening for a patient to be eligible. If no archival
tissue block is available and/or fewer than 15 unstained sections are available,
eligibility must be confirmed with the Coordinating Principal Investigator or
delegate.

9. Patients must have adequate haematological, renal, hepatic and pulmonary functions as
defined by:

- Absolute neutrophil count =1.5 x 109/L

- Haemoglobin = 10 g/L

- Platelet count =100 x 109/L

- Total serum bilirubin = 1.5 x upper normal limit

- Alanine aminotransferase (ALT) = 2.5 x upper normal limit or = 5 x upper limit of
normal if liver metastases are present

- Renal: A creatinine clearance rate of greater than 60 mL/minute

10. Have a performance status of 0 or 1 on the ECOG Performance Scale

11. Life expectancy greater than 3 months

12. Female patients of childbearing potential must be willing to use two methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 60 days after the last dose of study medication. Patients of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year.

13. Male patients should agree to use an adequate method of contraception starting with
the first dose of study therapy through 60 days after the last dose of study therapy.

14. Willing to comply with trial therapy and trial-related investigations and evaluations

15. Willing to consent to the use of their collected tumour specimen and blood samples as
detailed in the protocol for future scientific research including but not limited to
DNA, RNA and protein based biomarker detection

16. Patient is available for follow up throughout time on trial

17. Recovered from previous toxicities (except alopecia)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who are pregnant or lactating

2. More than 2 lines of previous chemotherapy in the advanced or metastatic setting

3. Previous radiotherapy to all sites of measurable disease without post-radiotherapy
progression

4. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the date of registration

5. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient's
participation for the full duration of the trial, or is not in the best interest of
the patient to participate, in the opinion of the treating investigator

6. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial

7. Patients with a history of non-compliance to medical regimens or who are considered
potentially unreliable or will be unable to complete the entire study

8. Surgery or over 40Gy radiation to the primary tumour within 6 weeks of date of
registration

9. Presence of symptomatic or uncontrolled brain or central nervous system metastases
which require radiotherapy, surgery or ongoing use of corticosteroids

10. Known HIV positive status, active hepatitis B or C

11. Patients requiring or undergoing concurrent treatment with live vaccines

12. Patients requiring or undergoing concurrent treatment with phenytoin

13. Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma
in-situ)

14. Common Terminology Criteria for Adverse Events of at least grade 2 neuropathy

15. Patient has hearing loss requiring a hearing aid or intervention indicated.

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
Suspended
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [2] 0 0
Austin Health - Heidelberg
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Alfred Hospital - Prahran
Recruitment hospital [5] 0 0
Sunshine Hospital Western Health - Sunshine
Recruitment postcode(s) [1] 0 0
3000 - Clayton
Recruitment postcode(s) [2] 0 0
3000 - Heidelberg
Recruitment postcode(s) [3] 0 0
3002 - Melbourne
Recruitment postcode(s) [4] 0 0
3000 - Prahran
Recruitment postcode(s) [5] 0 0
3000 - Sunshine

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine whether APR-246, 5-FU and cisplatin are safe and
effective in the treatment of platinum resistant oesophageal cancer.
Trial website
https://clinicaltrials.gov/show/NCT02999893
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Lara Lipton, MB.BS FRACP
Address 0 0
Peter MacCallum Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02999893