A Study of APR-246 in Oesophageal Cancer

• Status: Suspended
• Trial end date: 2019-10-07
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Peter MacCallum Cancer Centre, Australia

Criteria

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)

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.