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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with advanced pancreatic cancer that cannot be surgically removed. The researchers aim to determine the optimal dose and assess its safety and effectiveness, particularly for those with a specific type of pancreatic cancer called basal-like. The combination includes Erlotinib (Tarceva), Gemcitabine (Gemzar), and Nab paclitaxel (Abraxane). Participants with other types of pancreatic cancer will receive standard chemotherapy for comparison. The trial seeks participants whose cancer has spread and who have not previously received certain treatments for pancreatic cancer. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of erlotinib, gemcitabine, and nab-paclitaxel is supported by safety data. The FDA has already approved these drugs for treating pancreatic cancer. Studies have found that adding erlotinib or nab-paclitaxel to gemcitabine can extend the lives of people with advanced pancreatic cancer.

These treatments are generally well-tolerated, though they can have side effects, like many cancer treatments. Common side effects include tiredness and low blood counts, which are often manageable. This combination has been used in other studies and is considered safe and practical for people with advanced pancreatic cancer.

Prospective trial participants should discuss any concerns with their doctor, who can provide advice based on individual health and treatment goals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pancreatic cancer because they combine targeted therapies in a novel way. The combination of Erlotinib, Gemcitabine, and Nab-paclitaxel targets different aspects of cancer cell growth and survival, which might enhance treatment effectiveness. Unlike standard treatments that typically focus on a single pathway, this combination therapy aims to tackle the disease more comprehensively by using a multi-pronged approach. In particular, Erlotinib targets the epidermal growth factor receptor (EGFR), potentially offering benefits for patients with specific tumor types identified by the PurIST classifier. This personalized approach could lead to better outcomes and more precise treatment strategies.

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

Research has shown that a combination of three drugs—erlotinib, gemcitabine, and nab-paclitaxel—can extend the lives of patients with advanced pancreatic cancer. Studies have found that this combination improves survival rates more than gemcitabine alone. For instance, one study found that 35% of patients were alive after one year with the combination therapy, compared to 22% with just gemcitabine. In this trial, participants with basal-like tumors will receive the combination therapy of erlotinib, gemcitabine, and nab-paclitaxel. Another study also found that adding erlotinib and nab-paclitaxel to gemcitabine can extend patient survival. This suggests that the combination might be more effective than standard treatments for certain types of pancreatic cancer, such as the basal-like subtype. ^{1 2 4 6 7}

Who Is on the Research Team?

Ashwin Somasundaram, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1304369

Increased Survival in Pancreatic Cancer with nab ... The survival rate was 35% in the nab-paclitaxel–gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. ... The most common ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01010945

Erlotinib, Gemcitabine and Nab-Paclitaxel in Advanced ... This is a phase 1b study to evaluate the combination of gemcitabine and Tarceva (erlotinib) and nab-paclitaxel in patients with advanced pancreatic cancer.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26886016/

A phase 1b study of erlotinib in combination with ... Abstract. Purpose: Addition of either nab-paclitaxel or erlotinib to gemcitabine to treat advanced pancreatic cancer has demonstrated overall survival benefit.

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2014.32.3_suppl.353

Cost-effectiveness of nab-paclitaxel plus gemcitabine ... nab-P/G had higher 1 year OS (35% vs 22%) and improved PFS by 1.8 months (HR = 0.69, P < 0.01). nab-P/G is the first taxane based therapy to ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-00301

Erlotinib, Gemcitabine and Nab-Paclitaxel for the ... Giving erlotinib, gemcitabine and nab-paclitaxel may work better than standard chemotherapy in treating patients with metastatic basal-like pancreatic cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06483555

Basal-like PDAC Treated With Gemcitabine, Erlotinib, and ... However, the combinations of erlotinib, gemcitabine, and nab-paclitaxel are both approved by the FDA for the treatment of pancreatic cancer. The standard of ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00746

Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study TTFields therapy with gemcitabine ± nab-paclitaxel was feasible, safe, and active in patients with advanced pancreatic adenocarcinoma in the ...