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

Trial Summary

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 data supports the effectiveness of the treatment plan for high-risk pancreatic cancer?

Research shows that patients with pancreatic cancer who received personalized matched therapies based on their tumor's genetic profile lived longer than those who received standard treatments. Specifically, patients with highly actionable genetic changes who received matched therapy had a longer time before their cancer progressed. ^{1 2 3 4 5}

Is personalized therapy for high-risk pancreatic cancer safe for humans?

The research does not provide specific safety data for personalized therapy in pancreatic cancer, but it suggests that matching therapies to genetic changes in tumors may improve outcomes. However, the safety of these treatments in humans is not directly addressed in the available studies. ^{1 2 6 7 8}

How is the Personalized Therapy for High-Risk Pancreatic Cancer treatment different from other treatments?

This treatment is unique because it uses genomic profiling to tailor therapies specifically to the genetic alterations found in a patient's tumor, potentially leading to better outcomes compared to standard treatments that do not consider individual genetic differences. ^{1 2 3 9 10}

What is the purpose of this trial?

This is a prospective, open-label therapeutic interventional investigation designed to interrogate the efficacy and safety of individualized matched therapies in patients with pancreatic cancer at high risk of disease recurrence post-surgery.

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

Eligibility Criteria

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.

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Targeted Approach Succeeds in Pancreatic Cancer. [2021]

2. England 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Molecular Profiling of Patients with Pancreatic Cancer: Initial Results from the Know Your Tumor Initiative. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Molecular Targeting of a BRAF Mutation in Pancreatic Ductal Adenocarcinoma: Case Report and Literature Review. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Translational advances in pancreatic ductal adenocarcinoma therapy. [2023]

6. United States 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. [2023]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Systemic therapies for pancreatic cancer--the role of pharmacogenetics. [2022]

8. United States 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

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