A Study of APR-246 in Oesophageal Cancer

NCT02999893 | Terminated Phase 1 DMC

• 1 other identifier: 16/012
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 5

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.

Conditions

Oesophageal Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  3 weeks post commencement of treatment.

Secondary Outcomes (1)

• Evidence of clinical efficacy of a combined APR-246 and cisplatin/5FU chemotherapy regimen as confirmed by CT/PET/MRI scan.

  6 and 12 weeks post commencement of treatment.

Other Outcomes (1)

• Number of patients who will benefit from APR-246 therapy as assessed by quantitation of ctDNA levels in patient serum and plasma samples.

  Through study completion, an average of 7 years.

Study Arms (1)

APR-246

EXPERIMENTAL

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

Drug: APR-246

Interventions

APR-246 DRUG

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

APR-246

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 years or older at screening
• Histologically-confirmed metastatic or advanced oesophageal or oesophago-gastric junction adenocarcinoma or squamous cell carcinoma
• Radiologic disease progression at or within 6 months of platinum containing chemotherapy in the advanced/metastatic or adjuvant setting
• Measurable disease as per RECIST1.1 criteria
• Measurable lesions must not have previously had radiotherapy or must have progressed following radiotherapy
• 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.
• Patient has provided written informed consent for the trial
• 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.
• 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

You may not qualify if:

• Women who are pregnant or lactating
• More than 2 lines of previous chemotherapy in the advanced or metastatic setting
• Previous radiotherapy to all sites of measurable disease without post-radiotherapy progression
• 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
• 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
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• 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
• Surgery or over 40Gy radiation to the primary tumour within 6 weeks of date of registration
• Presence of symptomatic or uncontrolled brain or central nervous system metastases which require radiotherapy, surgery or ongoing use of corticosteroids
• Known HIV positive status, active hepatitis B or C
• Patients requiring or undergoing concurrent treatment with live vaccines
• Patients requiring or undergoing concurrent treatment with phenytoin
• Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma in-situ)
• Common Terminology Criteria for Adverse Events of at least grade 2 neuropathy
• Patient has hearing loss requiring a hearing aid or intervention indicated.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (5)

Monash Medical Centre

Clayton, Victoria, 3000, Australia

Location

Austin Health

Heidelberg, Victoria, 3000, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

Alfred Hospital

Prahran, Victoria, 3000, Australia

Location

Sunshine Hospital Western Health

Sunshine, Victoria, 3000, Australia

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

eprenetapopt

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Lara Lipton, MB.BS FRACP

  Peter MacCallum Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2016
• First Posted: December 21, 2016
• Study Start: April 11, 2017
• Primary Completion: October 16, 2020
• Study Completion: February 7, 2021
• Last Updated: December 13, 2021

Record last verified: 2021-12

Locations

AU (5)