Overview

Gemcitabine and Nab-Paclitaxel vs Gemcitabine, Nab-Paclitaxel, Durvalumab and Tremelimumab as 1st Line Therapy in Metastatic Pancreatic Adenocarcinoma

Status:
Active, not recruiting
Trial end date:
2022-01-31
Target enrollment:
0
Participant gender:
All
Summary
The standard or usual treatment for this disease consists of two chemotherapy drugs gemcitabine and nab-paclitaxel given together.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Canadian Cancer Trials Group
Collaborator:
AstraZeneca
Treatments:
Albumin-Bound Paclitaxel
Antibodies, Monoclonal
Durvalumab
Gemcitabine
Paclitaxel
Tremelimumab
Criteria
Inclusion Criteria:

- Patients must have histologically or cytologically confirmed pancreatic ductal
adenocarcinoma which is metastatic.

- Must have presence of measurable or evaluable disease as defined by Response
Evaluation Criteria in Solid Tumours (RECIST 1.1).

- Patients must be considered suitable candidates for, and able to receive, first line
chemotherapy for metastatic disease with gemcitabine and nab-paclitaxel.

- Patient must consent to provision of, and investigator(s) must confirm access to and
agree to submit within 4 weeks of randomization to the CCTG Central Tumour Bank, a
representative formalin fixed paraffin block of tumour tissue of adequate amount and
quality in order that the specific correlative marker assays proscribed in the
protocol may be conducted.

- Patient must consent to provision of samples of blood, serum and plasma in order that
the specific correlative marker assays proscribed may be conducted.

- Patients must be ≥ 18 years of age.

- Patients must have an ECOG performance status of 0 or 1 with a life expectancy of at
least 12 weeks.

- No prior treatment for metastatic disease is permitted. Patients may have received
prior adjuvant chemotherapy if the last dose was given more than 6 months prior to
recurrence. Patients may not have received chemoradiotherapy or adjuvant radiation
therapy. Patient may not have received nab-paclitaxel as adjuvant therapy. Prior
systemic treatment for borderline resectable or locally advanced disease is not
permitted. Patients receiving a single dose of radiation (up to 8Gy/800RAD) with
palliative intent for pain control are eligible provided a minimum of 14 days have
elapsed between the radiation and the date of randomization.

- Adequate normal organ and marrow function as defined below (must be done within 14
days prior to registration).

Absolute neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L Hemoglobin ≥90 g/L Bilirubin ≤
1.5 x upper normal limit AST and ALT ≤ 2.5 x upper normal limit Serum creatinine <1.25 UNL
or Creatinine clearance ≥40mL/min

- Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as
necessary to document all sites of disease done within 28 days prior to randomization.

- Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life
questionnaires in either English or French.

- Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements.

- Patients must be accessible for treatment and follow-up. Patients registered on this
trial must be treated and followed at the participating centre. Patients must agree to
return to the participating centre for management of any adverse events which may
occur through the course of the trial. This implies there must be reasonable
geographical limits placed on patients being considered for this trial. Sites are
encouraged to contact CCTG (or their respective Cooperative Group for sites outside
Canada) for any questions regarding the interpretation of this criterion.
Investigators must assure themselves the patients randomized on this trial will be
available for complete documentation of the treatment, adverse events, and follow-up.

- In accordance with CCTG policy, protocol treatment is to begin within 2 working days
of patient randomization.

- Women/men of childbearing potential must have agreed to use a highly effective
contraceptive method

Exclusion Criteria:

- Patients with a history of other malignancies, except: adequately treated non-melanoma
skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively treated with no evidence of disease for ≥ 5 years. Patients with a history
of other malignancies detected at an early stage and whom the investigator believes
have been curatively treated and are at a low risk of recurrence MAY be eligible.
Contact CCTG to discuss eligibility prior to enrolling.

- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an
anti-CTLA4, including tremelimumab.

- History of primary immunodeficiency, history of organ transplant that requires
therapeutic immunosuppression or prior history of severe (grade 3 or 4)
immune-mediated toxicity from other immune therapy.

- Current or prior use of immunosuppressive medication within 28 days before the first
planned dose of study therapy, with the exceptions of intranasal and inhaled
corticosteroids or systemic corticosteroids at physiological doses, which are not to
exceed 10 mg/day of prednisone, or an equivalent corticosteroid.

- 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, celiac disease or other serious gastrointestinal chronic
conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome (granulomatosis with polyangitis), rheumatoid arthritis,
hypophysitis, uveitis, etc. within the past 3 years prior to the start of treatment.
The following are exceptions to this criterion:

- Patients with alopecia

- Patients with Grave's disease, vitiligo or psoriasis not requiring systemic
treatment (within the last 2 years).

- Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on
hormone replacement.

NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic
treatment (within the past 2 years) are not excluded.

- Patients with active or uncontrolled intercurrent illness including, but not limited
to:

- cardiac dysfunction (symptomatic congestive heart failure, uncontrolled
hypertension, unstable angina pectoris, cardiac arrhythmia);

- active peptic ulcer disease or gastritis;

- active bleeding diatheses;

- psychiatric illness/social situations that would limit compliance with study
requirements or compromise the ability of the subject to give written informed
consent;

- known history of previous clinical diagnosis of tuberculosis;

- known human immunodeficiency virus infection (positive HIV 1/2 antibodies);

- known active hepatitis B infection (positive HBV surface antigen (HBsAg)).
Patients with a past or resolved HBV infection (defined as presence of hepatitis
B core antibody (anti-HBc) and absence of HBsAg) are eligible;

- known active hepatitis C infection. Patients positive for hepatitis C (HCV)
antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

- History of leptomeningeal carcinomatosis.

- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive
of but not limited to surgery, radiation and/or corticosteroids.

- Receipt of live attenuated vaccination (examples include, but are not limited to,
vaccines for measles, mumps, and rubella, live attenuated influenza vaccine (nasal),
chicken pox vaccine, oral polio vaccine, rotavirus vaccine, yellow fever vaccine, BCG
vaccine, typhoid vaccine and typhus vaccine) within 30 days prior to randomization.

- Pregnant or lactating women.

- Any active disease condition which would render the protocol treatment dangerous or
impair the ability of the patient to receive protocol therapy.

- Any condition (e.g. psychological, geographical, etc.) that does not permit compliance
with the protocol.

- History of hypersensitivity to gemcitabine, nab-paclitaxel, durvalumab or tremelimumab
or any excipient.