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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06290505




Registration number
NCT06290505
Ethics application status
Date submitted
18/10/2023
Date registered
4/03/2024

Titles & IDs
Public title
A Trial of Palliative Chemotherapy, Radiation and Immune Treatment for Oesophageal Cancer: PALEO Study
Scientific title
PALEO: Phase II Clinical Trial of Chemoradioimmunotherapy for the ALleviation of oEsOphageal Cancer Complications
Secondary ID [1] 0 0
PALEO
Universal Trial Number (UTN)
Trial acronym
PALEO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Oesophageal Cancer 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 - Durvalumab

Experimental: Treatment - Participants will receive 2 weeks of therapy with concurrent hypofractionated radiotherapy (30Gy/10#), weekly carboplatin (AUC2), weekly paclitaxel (50mg/m2) and durvalumab (1500mg) intravenously every 4 weeks, followed by durvalumab monotherapy continuing at 1500mg intravenously every 4 weeks until disease progression or 24 months of therapy. A single metastasis will be treated with stereotactic radiotherapy (24Gy/3#) 4 weeks after the completion of the chemoradiotherapy to the primary tumour. Monitoring of adherence to treatment will be done by attendance at booked appointments


Treatment: Drugs: Durvalumab
Durvalumab will be supplied by AstraZeneca as a 500 mg vial concentrate for solution for infusion. The solution contains 50 mg/mL durvalumab, 26 mM histidine/histidine-hydrochloride, 275 mM trehalose dihydrate, and 0.02% weight/volume (w/v) polysorbate 80; it has a pH of 6.0 and density of 1.054 g/mL. The label-claim volume is 10 mL.

Durvalumab is a sterile, clear to opalescent, colorless to slightly yellow solution, free from visible particles.

Investigational product vials are stored at 2°C to 8°C and must not be frozen. Investigational product must be kept in original packaging until use to prevent prolonged light exposure.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression free survival rate is the proportion of patients alive and progression free (the cancer has not worsened) assessed by CT Scan and clinical review.
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Duration of dysphagia relief
Timepoint [1] 0 0
Mellow score will be assessed at days 1, 8, 15, 29, 43, 57 and then every 4 weeks thereafter until the end of treatment visit (30days after the last dose).
Secondary outcome [2] 0 0
Nutritional status
Timepoint [2] 0 0
To be administered by a qualified dietician from date of randomisation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 96 weeks.
Secondary outcome [3] 0 0
Quality of life change using the - European organisation for the research and treatment of cancer quality of life questionnaire QLQ-C30
Timepoint [3] 0 0
Through study completion, an average of 1 year, using the 4-point ordinal scale - not at all, a little, quite a bit and very much
Secondary outcome [4] 0 0
Quality of life change using the - European organisation for the research and treatment of cancer quality of life questionnaire QLQ-OES18
Timepoint [4] 0 0
Through study completion, an average of 1 year, using the 4-point ordinal scale - not at all, a little, quite a bit and very much
Secondary outcome [5] 0 0
Response rate in metastatic lesions
Timepoint [5] 0 0
Assessment with imaging scans is performed at baseline then every 6 weeks while in treatment, then every 12 weeks until disease progression or date of death from any cause, whichever came first, assessed up to 96 weeks.
Secondary outcome [6] 0 0
Physician graded toxicity
Timepoint [6] 0 0
Assessed from baseline to 90 days following last treatment dose.
Secondary outcome [7] 0 0
SAE Rate
Timepoint [7] 0 0
Days 1, 8, 15, 29, 43, 57 and then every 4 weeks thereafter until to 100 days after last dose durvalumab regardless of relationship to drug.
Secondary outcome [8] 0 0
Overall survival.
Timepoint [8] 0 0
Throughout study completion, average 2 years

Eligibility
Key inclusion criteria
1. Males and females > 18 years of age.
2. Biopsy proven carcinoma of the oesophagus or gastro-oesophageal junction
3. Oligometastatic disease (1-5 lesions outside the primary tumour radiotherapy field on FDG-PET scan), or locoregionally advanced disease unsuitable for either surgical resection or radical chemoradiotherapy
4. Symptomatic dysphagia (Mellow score greater than 0)
5. ECOG performance status 0-2
6. Anticipated life expectancy of greater than 12 weeks.
7. Body weight of greater than 30kg.
8. Adequate bone marrow function, with values within the ranges specified below. Blood transfusions are permissible.

1. White blood cell count greater than or equal to 2 x (10 to the power of 9)/L
2. Absolute neutrophil count greater than or equal to 1.5 x (10 to the power of 9)/L
3. Platelets greater than or equal to 100 x (10 to the power of 9)/L
4. Haemoglobin greater than or equal to 90g/L
9. Adequate liver function, with values within the ranges specified below:

1. Alanine transferase less than or equal to 2.5 x upper limit of normal (ULN)
2. Aspartate transferase less than or equal to 2.5 x ULN
3. Total bilirubin less than or equal to 1.5 x ULN (except patients with Gilbert's Syndrome, who can have total bilirubin less than or equal to 5 x ULN)
10. Adequate renal function, with values within the ranges specified below. Note that an estimated renal function of greater than 125mL/min by the Cockroft-Gault formula must not be used for carboplatin dosing, and must instead be determined using a direct method.

1. Serum creatinine less than or equal to 1.5 x ULN
2. Creatinine clearance (CrCl) greater than or equal to 40 mL/min using Cockroft-Gault formula
11. Tumour tissue (formalin-fixed, paraffin embedded) should be available for PD-L1 and mismatch repair (MMR) protein expression and can be provided as a block or slides (archival tissue is acceptable). Blocks prepared from cytological samples, where tumour cell number is sufficient, are also acceptable. Patients will not be selected by PD-L1 or MMR status.
12. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
13. Signed, written and informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Bulky or organ-threatening metastatic disease requiring upfront higher dose chemotherapy in the judgement of the treating clinician.
2. Known tumour HER2 positivity (IHC 2+ or more and HER2 gene amplification on in situ hybridisation)
3. Previous systemic therapy for oesophageal or GOJ carcinoma.
4. Previous thoracic radiotherapy. Prior palliative radiotherapy to bony metastases is permitted.
5. Oesophageal stent in situ.
6. Known tracheo-oesophageal fistula.
7. Known leptomeningeal or brain metastases.
8. Major surgical procedure (as defined by the Investigator) within 28 days prior to first day of study treatment. Note: Local surgery of isolated lesions for palliative intent is permitted.
9. History of another malignancy within the last 3 years, with the exception of adequately treated non-melanomatous skin cancer, carcinoma in situ and superficial transitional cell carcinoma of the bladder.
10. Prior therapy with an anti-PD1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
11. Sensory neuropathy of grade 2 or higher severity per CTCAE v5.0.
12. History of allergy or hypersensitivity to study drug components, or other contraindications to any of the study drugs. Active or prior documented autoimmune disorders (including inflammatory bowel disease [e.g., ulcerative colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc). Patients with the following conditions are exceptions to this criterion:

1. Vitiligo or alopecia.
2. Hypothyroidism (e.g., following Hashimoto syndrome) stable on thyroid hormone replacement.
3. Any chronic skin condition (e.g. psoriasis) that does not require systemic therapy.
4. Type 1 diabetes mellitus.
5. Coeliac disease controlled by diet alone.

Patients without active autoimmune disease in the last 5 years may also be included but only after consultation with the Chief Principal Investigators.
13. Any condition requiring continuous systemic treatment with either regular corticosteroids (>10mg daily prednisone or equivalent dose of an alternative corticosteroid) or other immunosuppressive medications within 14 days of study drug administration. Intranasal, inhaled or topical steroids, and adrenal replacement steroid doses >10mg daily oral prednisone equivalent, are permitted in the absence of active autoimmune disease.
14. Positive test for hepatitis B surface antigen (HBsAg) indicating acute or chronic infection. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HBsAg) are eligible.
15. Positive test for hepatitis C virus antibody (HCV antibody) , unless polymerase chain reaction is negative for HCV RNA.
16. History of other significant, or active, infection, including HIV or tuberculosis (TB). HIV testing is not mandatory unless clinically indicated. Clinical evaluation for active TB may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice.
17. Receipt of a transplanted solid organ (kidney, liver, heart or lung) or of an allogeneic bone marrow transplant.
18. Receipt of a live attenuated vaccine within 30 days prior to registration.
19. Use of alternative or traditional medicines within 14 days prior to registration.
20. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events or compromise the ability of the patient to give written informed consent.
21. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception to avoid pregnancy for 90 days after the last dose of durvalumab. Women of childbearing potential must have a negative pregnancy test within 24 hours prior to trial registration. Men must have been surgically sterilized or use a double barrier method of contraception if they are sexually active with a woman of childbearing potential for a period of 180 days after the last dose of durvalumab and chemotherapy, or 90 days after the last dose of durvalumab monotherapy (whichever is the longer time period). Sperm donation is not permitted for 180 days after the last dose of durvalumab and chemotherapy, or 90 days after the last dose of durvalumab monotherapy (whichever is the longer time period).

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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 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
8/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2028
Actual
Sample size
Target
54
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Border Medical Oncology - Albury
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 0 0
St Vincent's Hospital - Fitzroy
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [7] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2298 - Newcastle
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
- Bedford Park
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
Australasian Gastro-Intestinal Trials Group
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Fiona Day, Dr
Address 0 0
Calvary Mater
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Miriam Roesner
Address 0 0
Country 0 0
Phone 0 0
02 7208 2727
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data sharing is encouraged and will be considered following submission of a concept for a secondary analysis


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06290505