Radiotherapy + Defactinib + Avutometinib for Pancreatic Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial aims to determine if combining radiotherapy with two drugs, defactinib and avutometinib, can help people with advanced pancreatic cancer live longer without disease progression. One group will receive only radiotherapy, while the other will receive radiotherapy plus the two drugs. Suitable participants have pancreatic cancer that cannot be easily removed by surgery and have completed at least two months of chemotherapy without cancer spreading. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.
Do I have to stop taking my current medications for the trial?
The trial protocol does not clearly specify if you must stop taking your current medications. However, you cannot take medications that interact with the trial drugs, like strong CYP3A4, CYP2C9, P-glycoprotein, or breast cancer resistance protein inhibitors or inducers, within 14 days before starting the trial. It's best to discuss your current medications with the trial team.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that combining defactinib and avutometinib may help treat cancer. In one study, 83% of patients with advanced pancreatic cancer responded positively to the treatment, suggesting its effectiveness and general tolerability for many. Another study found that 92% of patients responded at different dose levels, which is encouraging.
While these results are promising, it's important to remember that researchers are still testing these treatments for safety. The trials aim to learn more about possible side effects and how well patients can tolerate the drugs. Those considering joining a trial should consult their doctor for advice based on their health needs.12345Why are researchers excited about this trial's treatments?
Researchers are excited about combining defactinib and avutometinib with stereotactic body radiotherapy (SBRT) for pancreatic cancer because these drugs target cancer cells in a unique way. Unlike standard treatments that mainly rely on chemotherapy or surgery, defactinib and avutometinib work by inhibiting specific pathways that help cancer cells grow and spread. This combination therapy aims to enhance the effectiveness of SBRT, potentially leading to better outcomes by attacking the cancer on multiple fronts. Plus, with defactinib and avutometinib administered orally, it offers a more convenient treatment option compared to traditional intravenous therapies.
What evidence suggests that this trial's treatments could be effective for pancreatic cancer?
In this trial, participants will join different treatment arms to evaluate various approaches for pancreatic cancer. One arm will receive a combination of defactinib and avutometinib with stereotactic body radiotherapy (SBRT). Studies have shown promising results for this combination in treating pancreatic cancer. In a recent study, 83% of patients with advanced pancreatic cancer experienced tumor shrinkage or disappearance. Another study found that patients on this treatment had a period during which their cancer did not worsen. Additionally, 92% of evaluable patients responded positively to the treatment. These findings suggest that the combination of defactinib and avutometinib could potentially help manage advanced pancreatic cancer.12345
Who Is on the Research Team?
Patrick Grierson, M.
Principal Investigator
Washington University School of Medicine
Are You a Good Fit for This Trial?
Adults with advanced pancreatic adenocarcinoma who've had at least 2 months of chemotherapy without disease progression, expected to live more than 3 months, and have good heart function. They must not be pregnant or breastfeeding and agree to use contraception. Excludes those with certain medical conditions, recent major surgery, other cancer treatments within the last 2 years (unless cured), active infections, or known allergies to study drugs.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Radiation
Participants receive 5 fractions of adaptive stereotactic body radiotherapy (SBRT)
Treatment
Participants receive 12 cycles of oral defactinib and avutometinib, with cycles being 28 days each
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Avutometinib
- Defactinib
- Stereotactic Body Radiotherapy
Trial Overview
The trial tests if combining stereotactic body radiotherapy (SBRT) with defactinib and avutometinib improves survival in advanced pancreatic cancer patients compared to SBRT alone. Participants will receive adaptive SBRT alongside these medications.
How Is the Trial Designed?
2
Treatment groups
Experimental Treatment
Active Control
Participants will receive approximately 12 months of treatment on study with 5 fractions of adaptive SBRT with 12 cycles of oral defactinib + avutometinib beginning on Day 2 of radiation. Cycles are 28 days in length. Defactinib is dosed twice a day and avutometinib is dosed twice a week (e.g. Monday and Thursday, Tuesday and Friday, etc.) on a 3 weeks on, 1 week off schedule. The first 6 participants will be enrolled in the Safety Lead-In cohort to monitor for dose-limiting toxicities. Patients 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 patients will discontinue defactinib and avutometinib the day prior to the operation and will resume taking it 4 to 6 weeks after surgery for the remainder of the 12 cycles. Patients who are not candidates for surgical resection will continue to receive defactinib plus avutometinib uninterrupted.
Participants will receive 5 fractions of adaptive SBRT.
Find a Clinic Near You
Who Is Running the Clinical Trial?
Washington University School of Medicine
Lead Sponsor
Verastem, Inc.
Industry Sponsor
The Foundation for Barnes-Jewish Hospital
Collaborator
Citations
Avutometinib/defactinib and gemcitabine/nab-paclitaxel ...
Avutometinib/defactinib and gemcitabine/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: Initial safety and ...
2.
cancernetwork.com
cancernetwork.com/view/avutometinib-defactinib-combo-may-elicit-efficacy-in-metastatic-pdacAvutometinib/Defactinib Combo May Elicit Efficacy in ...
Additionally, the RP2D demonstrated the highest response rate across 5 dose cohorts, and 92% (n = 48 of 52) of all evaluable patients showed ...
Defactinib with avutometinib in patients with solid tumors
Key findings include an objective response rate of 42.3% (11 of 26; 95% confidence interval 23.4–63.1) and a median progression-free survival of ...
4.
investor.verastem.com
investor.verastem.com/news-releases/news-release-details/verastem-oncology-announces-positive-updated-results-ramp-205Press Release - Verastem, Inc.
Selected recommended Phase 2 dose: Dose level 1 demonstrated an ORR of 83% (10/12) in frontline metastatic pancreatic ductal adenocarcinoma.
NCT05669482 | Study of Avutometinib (VS-6766) + ...
This study will assess the safety and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients with ...
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