Stereotactic Body Radiotherapy Plus FAK and RAF/MEK Inhibition in Advanced Pancreatic Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorWashington University School of Medicine
About this trial
Advanced pancreatic cancer patients receiving treatment of adaptive stereotactic body radiotherapy (SBRT) with concurrent and adjuvant defactinib plus avutometinib will have increased progression-free survival (PFS) compared to historical PFS rates for patients receiving adaptive SBRT alone.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically or cytologically confirmed advanced pancreatic adenocarcinoma that is considered borderline resectable or locally advanced per institutional standardized criteria of unresectability or medical inoperability (NCCN guidelines 2.2021 PANC-C 1 of 2).
Patients with locoregional adenopathy are eligible as long as all suspicious lymph nodes are deemed to be adjacent to the primary tumor as per radiation oncologist assessment.
Patients must have received at least 2 months of systemic chemotherapy, such as FOLFOX, FOLFIRINOX, gemcitabine, nab-paclitaxel, cisplatin, or other regimens, for this disease without progression of local or systemic disease. Newly diagnosed patients may be screened for enrollment in this study and can be enrolled once they have completed 2 months of systemic chemotherapy (and still meet all eligibility criteria) prior to randomization. The last dose of chemotherapy must be ≥ 2 weeks prior to randomization.
At least 18 years of age.
Disqualifiers
A history of other malignancy with the exception of prior or concurrent malignancies whose natural history is unlikely to interfere with the safety or efficacy of the investigational regimen (in the opinion of the treating physician).
Clinically evident ascites or pleural effusion that requires therapeutic paracentesis or thoracentesis.
Prior treatment with a drug of the FAK inhibitor or RAF/MEK inhibitor class, or with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
Prior anti-human antibody response (AHA or ADA).
Trial design
Design model
Parallel
Treatments tested in this trial
Stereotactic body radiotherapy
RadiationMRIdian and Ethos (adaptive radiation platforms)
Defactinib
DrugTaken with 30 minutes of a meal
Avutometinib
DrugCan be taken without regard to food.
Treatment groups
36 Participants
are divided into 2 treatment groupsGroup A: Experimental Arm: SBRT + Defactinib + AvutometinibExperimental treatment 3 interventions
Group B: Control Arm: SBRTActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Progression-free survival (PFS) - Experimental Arm Only
Defined as the days from the date of standard of care (SOC) chemotherapy treatment start to progression or death.
Time frame
Through completion of follow-up (up to 2 years)Secondary outcomes
1
Number of patients with acute toxicity - Experimental Arm Only
Graded by CTCAE v. 5.0
Time frame
From start of treatment through 90 days2
Number of patients with late toxicity - Experimental Arm Only
Graded by CTCAE v. 5.0
Time frame
From day 91 through 2 years3
Local control - Experimental Arm Only
Time frame
At 12 months4
Distant metastasis progression-free survival (DM-PFS) - Experimental Arm Only
Defined as the days from the date of the SOC chemotherapy treatment to distant metastasis progression or death. The alive patients without distant metastasis progression are censored at the last follow-up.
Time frame
Through completion of follow-up (up to 2 years)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Washington University School of Medicine
Lead sponsor
Verastem, Inc.
Collaborator
The Foundation for Barnes-Jewish Hospital
Collaborator
Source ClinicalTrials.gov