Defactinib + Radiotherapy for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Washington University School of Medicine
Must not be taking: FAK inhibitors, Immunotherapy
Disqualifiers: Other malignancy, Immunodeficiency, Autoimmune, others
Stay on your current meds
No Placebo Group
Prior Safety Data
Approved in 4 jurisdictions
Trial Summary
What is the purpose of this trial?Patients with advanced pancreas adenocarcinoma will be randomized on a 6:1 basis to receive standard of care chemotherapy followed by adaptive stereotactic body radiotherapy (SBRT) with concurrent and adjuvant FAK inhibitor defactinib (experimental arm) or standard of care chemotherapy followed by SBRT (control arm). Patients enrolled to the experimental arm will be assessed for clinical outcomes such as progression free survival (PFS), local control, distant control, and toxicity. The first 6 patients randomized to the experimental arm will be considered the safety lead-in and will be assessed for dose-limiting toxicities (DLTs). The 6 patients randomized to the control arm will be evaluated for correlatives but will not be included in the analysis for primary and secondary endpoints.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require continued use of warfarin and cannot switch to another anticoagulant. Also, you should not have taken any investigational agents within 4 weeks before the trial.
What data supports the effectiveness of the treatment Defactinib + Radiotherapy for Pancreatic Cancer?
Research suggests that stereotactic ablative radiotherapy (SABR) can be a promising treatment for pancreatic cancer, offering high-dose, precise radiation that may improve disease control and quality of life for patients who cannot undergo surgery. This type of radiotherapy has shown potential benefits in local control and disease outcomes, making it a valuable option for those with locally advanced pancreatic cancer.
12345Is the combination of Defactinib and Stereotactic Body Radiotherapy safe for humans?
Stereotactic Ablative Radiotherapy (SABR) is generally considered safe, but gastrointestinal (GI) toxicity is a concern, meaning it can cause issues in the stomach and intestines. The safety of Defactinib specifically in combination with SABR for pancreatic cancer isn't detailed in the provided research, but SABR alone has been studied for its safety in pancreatic cancer treatment.
12367How is the treatment of Defactinib + Stereotactic Body Radiotherapy (SBRT) for pancreatic cancer different from other treatments?
The combination of Defactinib with Stereotactic Body Radiotherapy (SBRT) for pancreatic cancer is unique because SBRT delivers high-dose, precise radiation over a short period, potentially improving disease control and quality of life for patients who cannot undergo surgery or chemotherapy. This approach is particularly beneficial for those with localized pancreatic cancer, offering a novel option compared to traditional treatments.
138910Eligibility Criteria
Adults over 18 with advanced pancreatic adenocarcinoma that's borderline resectable or unresectable, who've had at least 3 months of chemo without disease progression. Participants must have a life expectancy over 3 months, adequate organ function, and agree to use effective contraception. Excluded are those with other recent cancers, certain health conditions like uncontrolled hypertension or active infections, prior FAK inhibitor treatment, known allergies to study drugs' components, or inability to swallow pills.Inclusion Criteria
My bone marrow and organs are functioning normally.
Your corrected QT interval is less than 480 milliseconds.
My blood clotting time is normal or managed with medication.
+16 more
Exclusion Criteria
I have had pneumonitis treated with steroids or have it now.
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry
I haven't needed systemic treatment for an autoimmune disease in the last 2 years.
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Chemotherapy
Participants receive standard of care chemotherapy
Estimated 12 weeks
Radiation
Participants receive 5 fractions of magnetic resonance adaptive stereotactic body radiation therapy (SBRT)
1 week
Treatment with Defactinib
Participants in the experimental arm receive 17 cycles of defactinib, each cycle lasting 21 days
Approximately 12 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Participant Groups
The trial is testing if adding the drug defactinib to standard chemotherapy and stereotactic body radiotherapy (SBRT) improves survival in patients with advanced pancreas cancer compared to SBRT alone. Patients will be randomly assigned in a ratio of 6:1 to either the experimental group receiving defactinib or the control group not receiving it.
2Treatment groups
Experimental Treatment
Active Control
Group I: Adaptive SBRT + DefactinibExperimental Treatment4 Interventions
* Participants in this study will receive 5 fractions of magnetic resonance adaptive stereotactic body radiation therapy (SBRT) and seventeen 21-day cycles of defactinib (beginning on Day 2 of radiation).
* Participants who are candidates for surgical resection will undergo standard of care surgery at 2 weeks post-end of SBRT (+/- 1 weeks) or 12 weeks post-end of SBRT (+/- 1 week). These participants will discontinue defactinib the day prior to the operation and will resume taking it for the remainder of the 17 cycles 4 to 6 weeks after surgery. Participants who are not candidates for surgical resection will continue to receive defactinib uninterrupted. All participants should receive 17 cycles of defactinib unless they experience disease progression or intolerable toxicity.
Group II: Adaptive SBRTActive Control2 Interventions
-Participants in this study will receive 5 fractions of magnetic resonance adaptive stereotactic body radiation therapy (SBRT)
Stereotactic Body Radiotherapy is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Stereotactic Body Radiation Therapy for:
- Lung cancer
- Liver cancer
- Spine tumors
- Pancreatic cancer
- Prostate cancer
🇺🇸 Approved in United States as Stereotactic Body Radiation Therapy for:
- Early-stage lung cancer
- Liver cancer
- Spine tumors
- Pancreatic cancer
- Prostate cancer
🇨🇦 Approved in Canada as Stereotactic Body Radiation Therapy for:
- Lung cancer
- Liver cancer
- Spine tumors
- Pancreatic cancer
- Prostate cancer
🇯🇵 Approved in Japan as Stereotactic Body Radiation Therapy for:
- Lung cancer
- Liver cancer
- Spine tumors
- Pancreatic cancer
- Prostate cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington University School of MedicineSaint Louis, MO
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
National Cancer Institute (NCI)Collaborator
Verastem, Inc.Industry Sponsor
References
Stereotactic ablative radiotherapy or best supportive care in patients with localized pancreatic cancer not receiving chemotherapy and surgery (PANCOSAR): a nationwide multicenter randomized controlled trial according to a TwiCs design. [2023]Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with 'best supportive care'. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible.
The Utility of Stereotactic Ablative Radiation Therapy for Palliation of Metastatic Pancreatic Adenocarcinoma. [2023]Our purpose was to report the outcome of stereotactic ablative radiation therapy (SABR) to the primary tumor for patients with metastatic pancreatic cancer.
Results of a prospective phase 2 clinical trial of induction gemcitabine/capecitabine followed by stereotactic ablative radiation therapy in borderline resectable or locally advanced pancreatic adenocarcinoma. [2023]Stereotactic ablative radiation therapy's (SABR's) great conformity and short duration has become an attractive treatment modality. We report a phase 2 clinical trial to evaluate efficacy and safety of induction chemotherapy (ICT) followed by SABR in patient with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).
Optimizing patient selection for stereotactic ablative radiotherapy in patients with locally advanced pancreatic cancer after initial chemotherapy - a single center prospective cohort. [2023]The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking.
Stereotactic body radiotherapy in the treatment of pancreatic cancer. [2022]Most patients diagnosed with pancreatic cancer are unable to have a curative surgical resection. Chemoradiation is a standard of care treatment for patients with locally advanced unresectable disease, but local failure rates are high with conventionally fractionated radiotherapy. However, stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy offers an alternative type of radiation therapy, which allows for the delivery of high-dose, conformal radiation. The high doses and shorter overall treatment time with SBRT may provide advantages in local control, disease outcomes, quality of life, and cost-effectiveness, and further investigation is currently underway. Here, we review the technology behind SBRT for pancreatic malignancy and its future direction in the overall management of pancreatic cancer.
Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity. [2018]Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. However, optimal dose planning and delivery strategies are unelucidated and gastro-intestinal (GI) toxicity remains a key concern.
Stereotactic body radiotherapy (SBRT) in recurrent or oligometastatic pancreatic cancer : A toxicity review of simultaneous integrated protection (SIP) versus conventional SBRT. [2022]Stereotactic body radiotherapy (SBRT) in pancreatic cancer can be limited by its proximity to organs at risk (OAR). In this analysis, we evaluated the toxicity and efficacy of two different treatment approaches in patients with locally recurrent or oligometastatic pancreatic cancer.
Phase 2 study of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy in patients with refractory pancreatic cancer (TRIPLE-R). [2023]Interleukin-6 blockade and radiation combined with immunotherapy may modulate the tumour microenvironment to overcome immune resistance. We assessed the efficacy of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy (SBRT) in patients with refractory pancreatic cancer (PC).
Neoadjuvant stereotactic body radiation therapy for nonmetastatic pancreatic adenocarcinoma. [2023]Background: Neoadjuvant therapy is a strategy for resectable and borderline resectable pancreatic cancer, but a consensus approach regarding optimal management is undetermined. Neoadjuvant options include chemotherapy with/without radiotherapy. Stereotactic body radiation therapy (SBRT) is a novel radiation technique that may provide benefit over conventionally fractionated radiation therapy (CFRT) in the neoadjuvant setting. The purpose of the present study is to determine neoadjuvant treatment with SBRT to other neoadjuvant treatment options for patients with resectable pancreatic cancer. Material and methods: The National Cancer Database was queried (2004-2015) for patients with nonmetastatic pancreatic adenocarcinoma receiving neoadjuvant therapy followed by pancreatectomy. Patients were categorized based on the type of neoadjuvant treatment administered. Statistics included temporal trend assessment by annual percent change (APC), predictors for SBRT by multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis without and with propensity matching, and Cox proportional hazards modeling for univariable OS analysis. Results: Of 5828 patients, 332 (5.7%), 3234 (55.5%) and 2262 (38.8%) received neoadjuvant chemo-SBRT, chemotherapy, and chemo-CFRT, respectively. SBRT utilization increased from 0% in 2004 to 9.5% in 2015, with a greater APC after 2010 (p < .001). SBRT was more likely to be utilized in patients with T3-4 and node-positive disease (p < .05 for all). The chemo-SBRT cohort was associated with a higher OS rate before and after propensity matching (p < .05 for both). The rate of R0 resection was higher in radiotherapy groups than the chemotherapy cohort (p < .001). Conclusions: Utilization of neoadjuvant SBRT for pancreatic cancer is increasing. In the neoadjuvant setting, chemo-SBRT may improve R0 resection and OS over chemotherapy and chemo-CFRT, although confirmatory prospective studies are needed for confirmation.
A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol. [2022]Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies shows the potential of neo-adjuvant chemo-radiotherapy but the relative radio-resistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic radiotherapy achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of clear resection margins and local disease control.