Personalized Therapy for High-Risk Pancreatic Cancer

(PROTECT-PANC Trial)

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Must not be taking: Investigational agents

Disqualifiers: Metastatic disease, Infections, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 6 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if personalized treatments can effectively and safely assist individuals with pancreatic cancer who face a high risk of recurrence after surgery. A specialized team of doctors will develop a treatment plan, known as Personalized Matched Targeted Therapies or Individualized Targeted Therapy, tailored to each person's specific cancer type. Suitable candidates for this trial have had their pancreatic tumors removed, have undergone certain therapies, and show signs of potential cancer recurrence, such as elevated cancer markers or specific surgical findings. As an unphased trial, this study provides a unique opportunity to explore innovative treatments tailored to individual needs.

Will I have to stop taking my current medications?

The trial requires that you stop taking other anti-tumor medications for at least five half-lives of the drug or three weeks, whichever is shorter, before starting the study treatment.

What prior data suggests that this treatment plan is safe for high-risk pancreatic cancer patients?

Research has shown that personalized treatments for pancreatic cancer, tailored to the genetic makeup of a patient's cancer, have shown promise in terms of safety. In one study, patients received these tailored treatments, which they generally tolerated well. While some patients experienced side effects, most were mild and manageable. The most common issues were tiredness and nausea, but these were not severe for most participants.

These personalized treatments are still under study. However, their testing in patients suggests reasonable safety so far. Always consult a healthcare provider about potential risks and benefits before considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the personalized therapy for high-risk pancreatic cancer because it takes a highly individualized approach, unlike standard treatments that often involve chemotherapy or radiation. This treatment leverages insights from a Molecular Tumor Board, which includes specialists like medical and surgical oncologists and pathologists, to tailor a treatment plan based on the specific genetic mutations in a patient's tumor. By focusing on the unique molecular features of each patient's cancer, this approach aims to target the disease more effectively than one-size-fits-all treatments. This precision strategy could lead to better outcomes and fewer side effects, offering new hope for those battling this aggressive cancer.

What evidence suggests that this trial's treatments could be effective for high-risk pancreatic cancer?

Research has shown that personalized treatments, designed based on an individual's unique genetic makeup, may aid in treating pancreatic cancer. In this trial, participants will receive a Molecular Tumor Board (MTB)-recommended matched therapy, where treatments align with specific changes in their tumors. Early results from previous studies suggest that this personalized approach could improve patient outcomes. Experts believe these targeted treatments might offer new hope for those with advanced pancreatic cancer, although further research is needed to confirm these benefits. ^{1 2 3 6 7}

Who Is on the Research Team?

Mandana Kamgar, MD, MPH

Principal Investigator

Medical College of Wisconsin

Razelle Kurzrock, MD

Principal Investigator

Medical College of Wisconsin

Douglas Evans, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for individuals who have had surgery for pancreatic cancer and are at high risk of the cancer coming back. Specific details about who can join or reasons why someone might not be eligible to participate are not provided.

Inclusion Criteria

My cancer is a type of pancreatic cancer, not related to neuroendocrine cells.

Laboratory values: Absolute neutrophil count (ANC) ≥ 1.0 × 109/L, Platelet count ≥ 75,000/mm^3 (125 × 109/L), Hemoglobin (Hgb) ≥ 8 g/dL, aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT), alanine transaminase (ALT) serum glutamate-pyruvate transaminase (SGPT) ≤ 5 × upper limit of normal range (ULN), Eastern Cooperative Oncology Group (ECOG) Performance Status < 3

I don't have visible cancer recurrence or spread after my first post-surgery scan.

Exclusion Criteria

Is pregnant or breastfeeding or any patient with childbearing potential not using adequate pregnancy prevention

I do not have any severe illnesses like heart problems or mental health issues that would stop me from following the study's requirements.

I cannot take pills by mouth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Molecular Profiling

Participants' tumor tissue or blood is molecularly profiled and discussed by the Molecular Tumor Board to recommend matched therapy

2-4 weeks

1 visit (in-person or virtual)

Treatment

Participants receive the Molecular Tumor Board-recommended matched therapy

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Treatment Plan

Trial Overview The study is looking into how safe and effective personalized treatments are for patients with pancreatic cancer that's likely to return after surgery. It involves giving therapies that match each patient's unique molecular profile.

How Is the Trial Designed?

Group I: Molecular Tumor Board (MTB)-recommended matched therapy Experimental Treatment 1 Intervention

The MTB, a multidisciplinary group composed of medical oncologists (including those with expertise in precision oncology), surgical oncologists, and a pathologist, convenes periodically to discuss and recommend an individualized treatment plan that targets specific molecular alterations (e.g., genomic mutations) found in the patient's cancer while considering patient clinical and laboratory factors.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

Recent advances in targeted therapy and immunotherapy show promise for treating pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed at advanced stages and has limited treatment options.

Combining these new therapies may enhance treatment effectiveness and improve patient outcomes, as supported by current preclinical and clinical evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational advances in pancreatic ductal adenocarcinoma therapy. Hosein, AN., Dougan, SK., Aguirre, AJ., et al.[2023]

Erlotinib, a targeted therapy that inhibits the epidermal growth factor receptor, has been approved for use alongside gemcitabine in treating advanced pancreatic cancer, marking a significant step in personalized cancer treatment.

Despite the exploration of various targeted agents, most have shown limited success, highlighting the need for therapies tailored to the specific molecular characteristics of both the patient and the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future strategies for targeted therapies and tailored patient management in pancreatic cancer. Ko, AH.[2018]

The Know Your Tumor (KYT) program successfully analyzed tumor samples from 640 pancreatic cancer patients, revealing actionable genomic alterations in 50% of cases, with 27% classified as highly actionable.

Patients with highly actionable biomarkers who received matched therapies experienced significantly longer progression-free survival (4.1 months) compared to those who received unmatched therapies (1.9 months), highlighting the potential benefits of precision medicine in treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Profiling of Patients with Pancreatic Cancer: Initial Results from the Know Your Tumor Initiative. Pishvaian, MJ., Bender, RJ., Halverson, D., et al.[2022]

In a study of 1856 pancreatic cancer patients, those with actionable molecular alterations who received matched therapy had a significantly longer median overall survival of 2.58 years compared to 1.51 years for those who received unmatched therapies.

The results indicate that precision medicine, which tailors treatments based on specific molecular profiles, can substantially improve survival outcomes in pancreatic cancer patients, highlighting the need for further research into these targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial. Pishvaian, MJ., Blais, EM., Brody, JR., et al.[2021]

A patient with advanced pancreatic ductal adenocarcinoma harboring a V600E BRAF mutation showed an objective tumor response to a combination treatment of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.

This case highlights the potential for targeted therapy in a small subset of pancreatic cancer patients, suggesting that BRAF mutations, although rare, may offer a new avenue for treatment beyond conventional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Targeting of a BRAF Mutation in Pancreatic Ductal Adenocarcinoma: Case Report and Literature Review. Seghers, AK., Cuyle, PJ., Van Cutsem, E.[2021]

In the retrospective Know Your Tumor trial, patients with pancreatic cancer who received targeted therapies based on specific genomic alterations in their tumors experienced longer survival compared to those treated with standard therapies.

This suggests that personalized treatment approaches, which match therapies to the genetic profile of tumors, may improve outcomes for pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Approach Succeeds in Pancreatic Cancer. [2021]

The study analyzed 51 pure pancreatic acinar cell carcinoma (PACC) specimens, revealing significant genomic differences from pancreatic ductal adenocarcinomas (PDAC), including lower MAPK signaling and less stromal cell abundance.

One patient with a BRAF-V600E mutation responded exceptionally well to targeted therapy with encorafenib and binimetinib, achieving a complete response lasting over 3 years, highlighting the potential for precision oncology in treating PACC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Genomic Analysis of Pancreatic Acinar Cell Carcinoma (PACC) and Pancreatic Ductal Adenocarcinoma (PDAC) Unveils New Actionable Genomic Aberrations in PACC. Florou, V., Elliott, A., Bailey, MH., et al.[2023]

The IMPaCT trial successfully identified actionable genomic targets in pancreatic cancer patients, screening 76 out of 93 enrolled patients and finding 22 candidates with specific mutations or amplifications that could be targeted with existing therapies.

The trial demonstrated that high-quality genomic data could be returned within a median time of 21.5 days, highlighting the feasibility of personalized medicine approaches in treating pancreatic cancer, although challenges such as biopsy acquisition and patient performance status were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial. Chantrill, LA., Nagrial, AM., Watson, C., et al.[2022]

Current treatments for advanced pancreatic cancer, including cytotoxic agents, have shown only modest survival benefits, highlighting the need for more effective therapies.

The review emphasizes the importance of pharmacogenetic investigations to identify predictive markers, which could lead to personalized treatment strategies that enhance efficacy and reduce toxicity for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapies for pancreatic cancer--the role of pharmacogenetics. Soo, RA., Yong, WP., Innocenti, F.[2022]

A patient with advanced, gemcitabine-resistant pancreatic cancer experienced a remarkable 36+ month tumor response after treatment with Mitomycin C, a DNA damaging agent, based on preclinical activity observed in a personalized xenograft of their tumor.

Genomic sequencing revealed a biallelic inactivation of the PALB2 gene, suggesting that this mutation may serve as a new biomarker for predicting response to DNA damage therapies in pancreatic cancer, highlighting the potential for personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. Villarroel, MC., Rajeshkumar, NV., Garrido-Laguna, I., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9860045/

Personalized matched targeted therapy in advanced ... We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06228599

Study Details | NCT06228599 | Molecular Profile-related ... This is a prospective, open-label therapeutic interventional investigation designed to interrogate the efficacy and safety of individualized matched therapies ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36670111/

Personalized matched targeted therapy in advanced ... We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board).

4. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-473204

Treatment Innovations in Pancreatic Cancer Targeted approach and immunotherapies hold promise to improve outcomes for patients with advanced pancreatic cancer, but need to be tested in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225000957

Medical management of pancreatic cancer This review examines recently implemented strategies to integrate predictive tools and targeted therapies to improve treatments personalization and patient ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204520300747

Overall survival in patients with pancreatic cancer receiving ... Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor ...

7. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2820691

Pancreatic Cancer Surveillance and Survival of High-Risk ... This cohort study compares survival of high-risk patients with screen-detected pancreatic cancer with a matched cohort from the Surveillance,