Targeted Drug Therapy for Pancreatic Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Charles D. Lopez

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: OHSU Knight Cancer Institute

Must not be taking: CYP3A inducers, CYP3A inhibitors

Disqualifiers: Uncontrolled infection, Cardiac disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing four experimental drugs to see if they can help treat pancreatic cancer. The drugs work by blocking important processes that cancer cells need to grow and survive. The trial focuses on patients with pancreatic cancer who do not respond well to standard treatments. Gemcitabine was the first agent investigated for its potential to improve symptoms and overall well-being in pancreatic cancer patients.

Will I have to stop taking my current medications?

The trial requires a 10-day period without taking any previous cancer treatments before starting the study drugs. Additionally, you cannot take certain medications that affect liver enzymes (CYP3A) or those that prolong the QT interval (a heart rhythm measure).

What evidence supports the effectiveness of the drug combination including Cobimetinib, Cotellic, LY3214996, Temuterkib, Olaparib, Lynparza, and Onvansertib for pancreatic cancer?

There is some evidence that the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib showed a positive tumor response in a patient with a specific type of advanced pancreatic cancer. However, overall, targeted therapies have not shown significant benefits for most pancreatic cancer patients, and the effectiveness of the specific drug combination in the trial is not directly supported by the available research. ^{1 2 3 4 5}

Is targeted drug therapy for pancreatic cancer generally safe in humans?

Cobimetinib, one of the drugs mentioned, was used in combination with another drug in a case report for pancreatic cancer, showing a tumor response, but specific safety data for this combination in humans is not detailed in the provided research. ^{2 5 6 7 8}

How is the drug combination of Cobimetinib, LY3214996, Olaparib, and Onvansertib unique for treating pancreatic cancer?

This drug combination is unique because it targets specific pathways and molecules involved in the growth and spread of pancreatic cancer cells, unlike traditional chemotherapy that attacks all rapidly dividing cells. Cobimetinib, for example, is a MEK inhibitor that has shown promise in targeting specific mutations in pancreatic cancer, offering a more tailored approach to treatment. ^{5 9 10 11 12}

Research Team

Charles D. Lopez

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

Adults (18+) with pancreatic cancer, either resectable or metastatic adenocarcinoma, who can consent to treatment and biopsies. They may be new to treatment or have had prior therapy with a specific washout period. Good organ function is required, and they must not be pregnant or breastfeeding. Contraception use is necessary for participants of childbearing potential.

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3) (within 4 weeks prior to initiating window treatment)

My cancer can potentially be cured with surgery.

Platelet count >= 100 x 10^9/L (> 100,000 per mm^3) (within 4 weeks prior to initiating window treatment)

Exclusion Criteria

I have a condition that affects my ability to swallow or absorb pills.

I am not pregnant or breastfeeding.

I am not taking strong or moderate drugs that affect liver enzymes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive assigned study agent (cobimetinib, olaparib, onvansertib, azenosertib, AZD5305, or tremelimumab) for 10 days, followed by biopsy or surgery

10 days

1 visit (in-person) for treatment, 1 visit (in-person) for biopsy/surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Cobimetinib (MEK/ERK Inhibitor)
• LY3214996 (MEK/ERK Inhibitor)
• Olaparib (PARP Inhibitor)
• Onvansertib (Other)

Trial Overview The trial tests the effectiveness of cobimetinib, olaparib, LY3214996 (temuterkib), and onvansertib in treating pancreatic cancer by comparing tissue samples before and after treatment. It's an early phase I trial designed to inform future trials based on biomarkers.

Participant Groups

Group I: Arm Tremelimumab Experimental Treatment 1 Intervention

Patients receive tremelimumab IV over 60 minutes one-time. Within 12-24 hours of cycle completion, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Group II: Arm Onvansertib Experimental Treatment 1 Intervention

Patients receive onvansertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease. (Arm Closed as of 8/12/2024)

Group III: Arm Olaparib Experimental Treatment 1 Intervention

Patients receive olaparib PO BID on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease. (Arm Closed as of 8/12/2024)

Group IV: Arm Cobimetinib Experimental Treatment 1 Intervention

Patients receive cobimetinib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease. (Arm Closed as of 8/12/2024)

Group V: Arm Azenosertib Experimental Treatment 1 Intervention

Patients receive azenosertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Group VI: Arm AZD5305 Experimental Treatment 1 Intervention

Patients receive AZD5305 PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Cobimetinib is already approved in Canada, Switzerland, Japan for the following indications:

Approved in Canada as Cotellic for:

• Melanoma

Approved in Switzerland as Cotellic for:

• Melanoma

Approved in Japan as Cotellic for:

• Melanoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

OHSU Knight Cancer Institute Portland, OR

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Patients Recruited

2,089,000+

American Association for Cancer Research

Collaborator

Trials

9

Patients Recruited

830+

Cardiff Oncology

Industry Sponsor

Trials

12

Patients Recruited

650+

Oregon Health and Science University

Collaborator

Trials

1024

Patients Recruited

7,420,000+

Genentech, Inc.

Industry Sponsor

Trials

1578

Patients Recruited

569,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New directions in the management of advanced pancreatic cancer: a review. Rocha-Lima, CM.[2022]

The combination of cediranib and olaparib did not show clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not have a known BRCA mutation, as no objective responses were observed in the study of 19 patients.

Despite some patients experiencing stable disease for a median of 3.1 months, the overall survival was only 3.4 months, indicating limited efficacy of this treatment combination in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. Kim, JW., Cardin, DB., Vaishampayan, UN., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small molecule inhibitors in pancreatic cancer. Sun, J., Russell, CC., Scarlett, CJ., et al.[2023]

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of erlotinib plus capecitabine as first-line treatment for metastatic pancreatic cancer (XELTA study). López, R., Méndez, CM., Fernández, MJ., et al.[2015]

In a phase II trial involving 17 patients with advanced pancreatic cancer, the combination of sorafenib and gemcitabine showed no objective responses, with only 18% of patients achieving stable disease.

The treatment resulted in a median overall survival of 4.0 months and was associated with significant toxicities, including thrombosis in 18% of patients, indicating that this combination is not effective for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. Kindler, HL., Wroblewski, K., Wallace, JA., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. Starling, N., Watkins, D., Cunningham, D., et al.[2022]

Dovitinib, when combined with gemcitabine and capecitabine, was found to be safe at a recommended dose of 300 mg daily, with manageable side effects such as fatigue and neutropenia in a study involving 29 patients with advanced pancreatic and biliary tract cancers.

The combination treatment showed promising efficacy, with partial responses observed in 5 patients, indicating potential benefits for those suffering from advanced pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of the FGFR/VEGFR Inhibitor Dovitinib With Gemcitabine and Capecitabine in Advanced Solid Tumor and Pancreatic Cancer Patients. Ma, WW., Xie, H., Fetterly, G., 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]

In a study involving 745 patients with advanced pancreatic cancer, adding the EGFR-targeted drug cetuximab to standard gemcitabine therapy did not significantly improve overall survival compared to gemcitabine alone, with median survival times of 6.3 months versus 5.9 months, respectively.

Despite 90% of patients showing positive EGFR expression, there was no observed treatment benefit from cetuximab, suggesting that targeting EGFR may not be effective and highlighting the need to explore alternative therapeutic targets for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. Philip, PA., Benedetti, J., Corless, CL., et al.[2022]

Erlotinib, a small molecule tyrosine kinase inhibitor, is approved for treating advanced lung adenocarcinoma and pancreatic cancer, highlighting its efficacy in targeting the EGFR pathway.

Cetuximab, an antibody targeting EGFR, is registered for metastatic colorectal cancer and head and neck cancers, indicating the broad potential of EGFR-targeting therapies in various cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy of the epidermal growth factor receptor in the treatment of pancreatic cancer. Heeger, S.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

New directions in the management of advanced pancreatic cancer: a review. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Small molecule inhibitors in pancreatic cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Translational advances in pancreatic ductal adenocarcinoma therapy. [2023]

5. France pubmed.ncbi.nlm.nih.gov

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

6. Greece pubmed.ncbi.nlm.nih.gov

Phase II trial of erlotinib plus capecitabine as first-line treatment for metastatic pancreatic cancer (XELTA study). [2015]

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

Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. [2022]

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

Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. [2022]

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

A Phase Ib Study of the FGFR/VEGFR Inhibitor Dovitinib With Gemcitabine and Capecitabine in Advanced Solid Tumor and Pancreatic Cancer Patients. [2022]

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

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

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

Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Targeted therapy of the epidermal growth factor receptor in the treatment of pancreatic cancer. [2019]