Combination Therapy for Pancreatic Cancer

(PANGEA Trial)

Overseen By Catherine A Griffin

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must be taking: EGFR inhibitors

Disqualifiers: Non-measurable disease, Prior therapy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

104 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug combination therapy for pancreatic cancer?

Research shows that combining nab-paclitaxel (Abraxane) with gemcitabine improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. Additionally, adding erlotinib to gemcitabine has shown benefits in patients with advanced pancreatic cancer. ^{1 2 3 4 5}

Is the combination therapy for pancreatic cancer safe for humans?

The combination of erlotinib (Tarceva) and gemcitabine (Gemzar) has been associated with side effects like diarrhea and rash, while nab-paclitaxel (Abraxane) has shown an acceptable safety profile in patients with advanced pancreatic cancer. ^{3 6 7 8 9}

How is the drug combination of Erlotinib, Gemcitabine, and Nab-paclitaxel unique for treating pancreatic cancer?

This drug combination is unique because it combines Erlotinib, which targets specific cancer cell receptors, with Gemcitabine and Nab-paclitaxel, which work together to enhance the killing of cancer cells. This approach aims to improve survival rates in pancreatic cancer, which is typically resistant to treatment. ^{2 3 7 10 11}

What is the purpose of this trial?

This study explores the best dose of the combination treatment for subjects with advanced unresectable or metastatic basal-like subtype pancreatic adenocarcinoma. For that reason, the safety, efficacy, and tolerability, as well as preliminary estimates of anti-tumor effects of low-dose epidermal growth factor receptor EGFR inhibitors in combination with bi-weekly gemcitabine/nab-paclitaxel (GnP) will be examined in subjects with advanced basal-like pancreatic adenocarcinoma. The Purity Independent Subtyping of Tumors (PurIST) will determine the type of cancer either "basal type" or "classical". If cancer subtype-based first-line chemotherapy in combination with erlotinib will be safe and tolerable in subjects with advanced unresectable or metastatic pancreatic adenocarcinoma of the basal-like subtype as defined by PurIST, as well as provide a preliminary assessment of treatment response in basal-like subjects. This study will also follow a subset of subjects with classical subtypes that are treated per standard of care on oxaliplatin-based triplet chemotherapy.

Research Team

Ashwin Somasundaram, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with advanced basal-like subtype pancreatic adenocarcinoma that cannot be surgically removed or has spread. Participants must have their cancer type confirmed as 'basal type' by the PurIST test and should not have had prior chemotherapy for metastatic disease.

Inclusion Criteria

I am fully active or can carry out light work.

Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information

Subject must consent to a mandatory pre-study biopsy if archival tissue is not available or sufficient

Exclusion Criteria

I was diagnosed with brain metastasis in the last 4 weeks.

My cancer is not confirmed as metastatic pancreatic adenocarcinoma.

Disease is not measurable according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy with gemcitabine, erlotinib, and nab-paclitaxel for basal-like subtype or standard-of-care triplet chemotherapy for classical subtype

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

2 years

Treatment Details

Interventions

• Erlotinib
• Gemcitabine
• Nab paclitaxel

Trial Overview The study tests a combination of low-dose EGFR inhibitors with bi-weekly gemcitabine/nab-paclitaxel to determine safety, tolerability, and preliminary anti-tumor effects in patients with basal-like pancreatic adenocarcinoma. It also observes subjects with classical subtypes receiving standard oxaliplatin-based chemotherapy.

Participant Groups

Group I: PurIST Basal Experimental Treatment 3 Interventions

Subjects will be screened using the PurIST classifier and "basal-like" tumors will be assigned combination therapy with GnP and erlotinib.

Group II: PurIST Classical Active Control 2 Interventions

Subjects will be screened using the PurIST classifier and with classical tumors will be treated per standard of care on triplet therapy.

Erlotinib is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Tarceva for:

• Non-small cell lung cancer
• Pancreatic cancer

Approved in United States as Tarceva for:

• Non-small cell lung cancer
• Pancreatic cancer

Approved in Canada as Tarceva for:

• Non-small cell lung cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Findings from Research

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

Recent treatment regimens for advanced pancreatic cancer, including gemcitabine, FOLFIRINOX, and nab-paclitaxel, have shown varying levels of efficacy, highlighting the importance of understanding their unique safety profiles.

Nurses play a crucial role in patient education and symptom management, as each treatment regimen has different adverse events that need to be identified and managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. Hronek, JW., Reed, M.[2017]

Itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel and gemcitabine, showed an acceptable safety profile and clinical activity in patients with advanced solid tumors, including pancreatic cancer, with a 24% overall response rate across various doses.

The study indicated that while itacitinib was tolerated at lower doses, treatment-related toxicities such as neutropenia and fatigue were common, leading to dose adjustments; however, the study was terminated early due to negative results from a related phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Beatty, GL., Shahda, S., Beck, T., et al.[2022]

A combination of gemcitabine and erlotinib has been shown to provide a survival advantage in patients with locally advanced and metastatic pancreatic cancer compared to gemcitabine alone, highlighting its efficacy in a disease known for poor outcomes.

Erlotinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor, demonstrates anti-tumor activity when used alongside gemcitabine, suggesting a promising mechanism of action in treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of erlotinib in the management of pancreatic cancer. Starling, N., Neoptolemos, J., Cunningham, D.[2021]

References

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

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

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

Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. [2023]

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

Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Erlotinib: success of a molecularly targeted agent for the treatment of advanced pancreatic cancer. [2018]

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

Erlotinib/gemcitabine for first-line treatment of locally advanced or metastatic adenocarcinoma of the pancreas. [2022]

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

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. [2017]

9. England pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]

10. Greece pubmed.ncbi.nlm.nih.gov

Does erlotinib restore chemosensitivity to chemotherapy in pancreatic cancer? A case series. [2015]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Role of erlotinib in the management of pancreatic cancer. [2021]