Trial Title:
NEO-adjuvant Chemo-immunotherapy in Pancreatic Cancer
NCT ID:
NCT06094140
Condition:
Pancreatic Cancer
Conditions: Official terms:
Pancreatic Neoplasms
Leucovorin
Oxaliplatin
Fluorouracil
Irinotecan
Durvalumab
Calcium
Levoleucovorin
Conditions: Keywords:
Resectable
Border-line
Pancreas
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 (36°F to 46°F) and must not be
frozen. Investigational product must be kept in original packaging until use to prevent
prolonged light exposure.
Arm group label:
Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.
Other name:
Imfinzi
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
85mg/m2 intravenously on day 1
Arm group label:
Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.
Other name:
Eloxatin
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
150mg/m2 intravenously on day 1
Arm group label:
Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.
Other name:
Camptosar
Other name:
Campto
Intervention type:
Drug
Intervention name:
Calcium folinate (leucovorin)
Description:
50mg as an intravenous bolus
Arm group label:
Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.
Other name:
Folinic acid
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
2400mg/m2 by continuous infusion via pump over 46 hours starting on day 1
Arm group label:
Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.
Other name:
Adrucil
Intervention type:
Drug
Intervention name:
Pegylated G-CSF
Description:
6mg by subcutaneous injection to be given on day 3 of each cycle.
Arm group label:
Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.
Other name:
Neulasta
Summary:
To determine the safety and tolerability of adding durvalumab to mFOLFIRINOX prior to
surgery in patients with resectable or borderline resectable pancreatic adenocarcinoma.
Detailed description:
Despite curative surgery, pancreatic cancer patients have five-year survival rates of
20%. Adjuvant chemotherapy has improved survival in resected pancreatic cancer patients
but only 10-15% are suitable for surgery and 30% of the resected pancreatic cancer
patients miss out on adjuvant chemotherapy due to postoperative complications.
Neoadjuvant chemotherapy has improved the resection rates in the patients with
non-metastatic pancreatic cancer. There is a growing interest to combine chemotherapy
with checkpoint inhibitors to improve disease control in the early stage of pancreas
cancer. The investigators propose a pilot study to evaluate the feasibility and safety of
combining modified FOLFIRINOX (mFOLFIRINOX) with durvalumab (MEDI4736) in patients with
resectable or borderline resectable pancreatic adenocarcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Adults, aged 18 years and older, with cytologically or histologically proven
resectable or borderline resectable pancreatic adenocarcinoma as per Australasian
Gastro-Intestinal Trials Group (AGITG) consensus guidelines. Those in whom cytology
is suspicious for pancreatic adenocarcinoma but not diagnostic may be allowed on
study following discussion with the study chair (or their representative).
2. ECOG 0-1
3. Adequate normal organ and marrow function as defined below:
- Haemoglobin ≥9.0 g/dL
- Absolute neutrophil count (ANC) ≥1.5 × 109 /L
- Platelet count ≥100× 109/L
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). [This will
not apply to patients with confirmed Gilbert's syndrome (persistent or
recurrent hyperbilirubinemia that is predominantly unconjugated in the absence
of hemolysis or hepatic pathology), who will be allowed only in consultation
with their physician.]
- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional ULN unless;
o There has been recent biliary drainage in the past 30 days, in which case it
must be ≤5 x ULN
- Measured creatinine clearance (CL) >50 mL/min or Calculated creatinine CL >50
mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
urine collection for determination of creatinine clearance: Males: Creatinine
CL (mL/min) = Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL)
Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 / 72 x serum
creatinine (mg/dL)
4. Study treatment both planned and able to start within 14 days of registration.
5. Body weight >30 kg.
6. Patient is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow up.
7. Must have a life expectancy of at least 12 weeks.
8. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging
(MRI) must be performed within 28 days prior to first study treatment.
9. Signed, written informed consent.
Exclusion Criteria:
1. Locally advanced or metastatic pancreatic adenocarcinoma.
2. Neuroendocrine pancreatic carcinoma.
3. Prior treatment for pancreatic cancer including chemotherapy, checkpoint inhibitor
or investigational treatments, the exception of a maximum of 1 cycle of neoadjuvant
intent mFOLFIRINOX.
4. Participation in another clinical study with an investigational product during the
last 30 days.
5. Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or enrolment occurs during the follow-up period.
6. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
replacement therapy) is acceptable.
7. Major surgical procedure (as defined by the Investigator) within 28 days prior to
the first dose of IP.
8. History of allogenic organ transplantation.
9. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to
this criterion:
1. Patients with vitiligo or alopecia.
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement.
3. Any chronic skin condition that does not require systemic therapy.
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician.
5. Patients with coeliac disease controlled by diet alone.
10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, active infection requiring systemic therapy within 14 days before the
first dose of study drug, 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 AEs or compromise the ability
of the patient to give written informed consent.
11. History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease ≥5
years before the first dose of IP and of low potential risk for recurrence.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
12. History of leptomeningeal carcinomatosis.
13. History of active primary immunodeficiency.
14. Active infection including:
1. Positive test for human immunodeficiency virus (HIV) (positive HIV 1/2
antibodies)
2. Active tuberculosis infection (clinical evaluation that may include clinical
history, physical examination and radiographic findings, or tuberculosis
testing in line with local practice)
3. Active hepatitis infection, positive hepatitis C virus (HCV) antibody,
hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (HBcAb or
anti-HBc), at screening. Participants with a past or resolved HBV infection
(defined as the presence of HBcAb or anti HBc and absence of HBsAg) are
eligible. Participants positive for HCV antibody are eligible only if
polymerase chain reaction is negative for HCV RNA
15. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection).
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent.
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication).
4. For patients enrolling after receipt of 1 cycle of mFOLFIRINOX, steroids given
pre and post chemotherapy as part of routine care.
16. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and
up to 30 days after the last dose of IP.
17. Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab.
18. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
19. Prior randomisation or treatment in a previous durvalumab clinical study regardless
of treatment arm assignment.
20. Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions and
requirements.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
GenesisCare North Shore
Address:
City:
Sydney
Zip:
2065
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Kathryn Jenkins
Investigator:
Last name:
Sarah Maloney
Email:
Principal Investigator
Facility:
Name:
Wollongong Hospital
Address:
City:
Wollongong
Zip:
2500
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Carly Leighton
Investigator:
Last name:
Lorraine Chantrill
Email:
Principal Investigator
Facility:
Name:
Warringal Private Hospital
Address:
City:
Melbourne
Zip:
3084
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Yuan Guo
Investigator:
Last name:
Niall Tebbutt
Email:
Principal Investigator
Start date:
May 20, 2022
Completion date:
June 2026
Lead sponsor:
Agency:
Australasian Gastro-Intestinal Trials Group
Agency class:
Other
Collaborator:
Agency:
The University of New South Wales
Agency class:
Other
Collaborator:
Agency:
Walter and Eliza Hall Institute of Medical Research
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/NCT06094140
