Trial Title:
A Trial of Palliative Chemotherapy, Radiation and Immune Treatment for Oesophageal Cancer: PALEO Study
NCT ID:
NCT06290505
Condition:
Esophageal Cancer
Conditions: Official terms:
Durvalumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
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.
Arm group label:
Treatment
Other name:
Imfinzi
Summary:
The purpose of this study is to investigate the effects of the addition of the
stereotactic body radiotherapy and durvalumab to a well tolerated 2 week chemotherapy and
radiation treatment regimen in people with esophageal cancer that is locally advanced or
has spread to another area of the body (metastasized).
Detailed description:
The purpose of this study is to investigate the effects of the addition of the
stereotactic body radiotherapy and durvalumab to a well tolerated 2 week chemotherapy and
radiation treatment regimen in people with esophageal cancer that is locally advanced or
has spread to another area of the body (metastasized).
Who is it for?
Participant may be eligible for this study if participant is an adult who has cancer of
the esophagus or gastro-esophageal junction that is locally advanced or has spread to
other parts of the participant's body.
Study details
All participants in this study will receive 10 treatments of radiotherapy to the primary
esophageal cancer, with one treatment given on each working day for two weeks. In
addition, all participants will receive chemotherapy (including carboplatin and
paclitaxel) given intravenously once per week for the same two weeks as the radiotherapy.
Durvalumab, an immune therapy, received intravenously; will be given every four weeks
from the beginning of radiation therapy.
After this participants will continue to receive immune therapy (durvalumab), received
intravenously once every 4 weeks for up to 24 months or until the cancer worsens. If
participants have a metastatic tumour, they will also be given 3 doses of radiotherapy in
one week. This radiotherapy will be received 4 weeks after the initial radiotherapy is
completed.
Safety blood tests will be collected throughout the study (every two weeks from week 2 of
treatment and then every four weeks from week 9 throughout the treatment and at other
times if clinically indicated). CT scans to evaluate the response to treatment will be
done every 6 weeks up to week 24 of treatment and then every 12 weeks or until the cancer
worsens. Study participants will also be asked to complete some questionnaires about
their wellbeing and nutritional status periodically throughout the study.
It is hoped that this trial can help determine if this chemotherapy with immune therapy
and radiotherapy combination is effective in increasing the ability of the body's immune
system to prevent worsening of the cancer and improve swallowing.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Males and females > 18 years of age.
2. Biopsy proven adenocarcinoma or squamous cell carcinoma of the esophagus 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.
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) if oligometastatic disease.
3. Previous systemic therapy for oesophageal or GOJ carcinoma.
4. Previous thoracic radiotherapy. Prior palliative radiotherapy to bony metastases is
permitted.
5. Esophageal 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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Border Medical Oncology
Address:
City:
Albury
Zip:
2640
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Jacqui McBurnie
Email:
jacqui.mcburnie@bordermedonc.com.au
Facility:
Name:
Calvary Mater Newcastle
Address:
City:
Newcastle
Zip:
2298
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Kim Adler
Email:
paleo@calvarymater.org.au
Facility:
Name:
Royal Brisbane and Women's Hospital
Address:
City:
Herston
Zip:
4029
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Jacqui Keller
Email:
jacqui.keller@health.qld.gov.au
Facility:
Name:
Flinders Medical Centre
Address:
City:
Bedford Park
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Aleksandra Kuruni, Dr
Email:
Aleksandra.Kuruni@sa.gov.au
Facility:
Name:
St Vincent's Hospital
Address:
City:
Fitzroy
Zip:
3065
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Nadia Ranieri
Email:
Nadia.RANIERI@svha.org.au
Facility:
Name:
Peter MacCallum Cancer Centre
Address:
City:
Melbourne
Zip:
3000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Shandelle Norman
Email:
Shandelle.Norman@ctaust.org
Facility:
Name:
Sir Charles Gairdner Hospital
Address:
City:
Nedlands
Zip:
6009
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Aylin Yahya
Email:
Aylin.Yahya@health.wa.gov.au
Facility:
Name:
Auckland Hospital
Address:
City:
Grafton
Zip:
1023
Country:
New Zealand
Status:
Recruiting
Contact:
Last name:
Sophie Goodger
Email:
SophieGo@adhb.govt.nz
Start date:
December 8, 2021
Completion date:
July 31, 2029
Lead sponsor:
Agency:
Australasian Gastro-Intestinal Trials Group
Agency class:
Other
Source:
Australasian Gastro-Intestinal Trials Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06290505