Pancreatic Adenocarcinoma Signature Stratification for Treatment

Brief summary public domain (ClinicalTrials.gov)

This is a randomized multicentre phase II trial with a large translational component. The trial will evaluate the two standard chemotherapy regimens: modified folfirinox (mFFX) and gemcitabine/nab-paclitaxel (GA), in patients with untreated metastatic pancreatic ductal adenocarcinoma. Integrated into this phase II trial are a number of laboratory components including molecular profiling, patient derived organoid establishment, and drug testing sensitivity and other biomarkers.

Detailed description public domain (ClinicalTrials.gov)

The two chemotherapy regimens GA and mFFX remain standard treatment options without biomarkers to predict response. PASS-01 will for the first time explore progression free survival differences in the two standard backbone regimens used in the advanced setting. Biomarker driven strategies in pancreatic ductal adenocarcinoma (PDAC) are lacking, perhaps accounting for a large number of failed phase II studies. This study will evaluate two standard of care chemotherapy regimens, but will also explore high content molecular profiling, chemotherapy sensitivity signatures, GATA6 and other putative biomarkers as predictors of response to chemotherapy. In addition, the use of patient derived organoid models for personalized medicine in PDAC will continue to develop within this study. Approximately 150 patients diagnosed with untreated metastatic pancreatic cancer will be randomized to either arm.

Intervention public domain (ClinicalTrials.gov)

Drug: Folfirinox. Chemotherapy

Intervention public domain (ClinicalTrials.gov)

Drug: Gemcitabine/nab-paclitaxel. Chemotherapy

Arm public domain (ClinicalTrials.gov)

Modified Folfirinox (active comparator): Modified FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin) administered intravenously. Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.

Arm public domain (ClinicalTrials.gov)

Gemcitabine/nab-Paclitaxel (active comparator): Gemcitabine/nab-Paclitaxel administered intravenously. Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.

Primary outcome public domain (ClinicalTrials.gov)

Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial.. Time from the date of randomization to progression based on the radiology assessment of response using RECIST v1.1, or death, whichever is earlier Time frame: 2-4 years.

Secondary outcome public domain (ClinicalTrials.gov)

ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA. Time frame: 2-4 years.

Secondary outcome public domain (ClinicalTrials.gov)

Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping. Time frame: 2-4 years.

Secondary outcome public domain (ClinicalTrials.gov)

GATA6 as a biomarker of response to mFFX or GA. Time frame: 2-4 years.

Secondary outcome public domain (ClinicalTrials.gov)

• Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics). Time frame: 2-4 years.

Secondary outcome public domain (ClinicalTrials.gov)

• Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics).. Time frame: 2-4 years.

Secondary outcome public domain (ClinicalTrials.gov)

• Correlation of individual tumour cytokeratins (eg. CK5 and CK17 expression) with chemotherapy response and resistance. Time frame: 2-4 years.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: 1. Patients must have a histological or radiological diagnosis of untreated metastatic PDAC at screening with histology subsequently confirmed prior to randomization. 2. Eligible histologic variants include adenocarcinoma or variants to include mucinous adenocarcinoma or adenosquamous carcinoma. 3. Patients with a history of prior or concurrent second primary malignancy whose natural history or treatment does not have the potential to interfere with the safety or primary endpoint efficacy assessment of the pancreas cancer should generally be eligible for enrollment in clinical trials. 4. Age ≥18 years. 5. Patient must have a tumor lesion that is amenable to a core needle biopsy. 6. Patients must be suitable for treatment with either mFFX and GA without contraindications to either regimen. 7. Eastern Cooperative Group (ECOG) performance status 0-1. (Karnofsky ≥70%). 8. Life expectancy of greater than 90 days, as judged by the investigator 9. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test and must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 10. Within 14 days of the proposed randomization date, patients must have normal organ and marrow function Exclusion Criteria: 1. Patients who have received prior systemic treatment for PDAC, including treatment in the neoadjuvant or adjuvant setting. Prior surgery or palliative radiation is permitted. 2. Patients with histology other than pancreatic ductal adenocarcinoma. Those with adenosquamous are allowed. Acinar tumors and colloid are excluded. 3. Patients with one or more contraindications to tumor biopsy according to local institution's standard biopsy procedures. 4. Patients with known brain metastases are excluded from participation in this clinical study. 5. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, inability to stop anticoagulation medication for a biopsy, or psychiatric illness/social situations that would limit compliance with study requirements. 6. Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures. 7. Patients with a known germline mutation in BRCA, PALB2 or …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 150 participants (actual).