Chemotherapy for Pancreatic Cancer

Overseen By Joyce Schaffer, RN, MSN, AOCNS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: HonorHealth Research Institute

Must not be taking: Non-FDA cannabinoids, QT prolonging

Disqualifiers: Metastatic disease, HIV, Hepatitis, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy drugs to determine their effectiveness for people with non-metastatic pancreatic cancer. Researchers aim to discover if this treatment can lower CA 19-9, a blood marker often elevated in individuals with this cancer type. The trial includes drugs such as Cisplatin, Gemcitabine, and Paclitaxel protein bound. It suits individuals diagnosed with pancreatic cancer that hasn't spread and who haven't received prior chemotherapy or radiation. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that patients on anticoagulation can be included at the discretion of the investigator. Additionally, non-FDA approved cannabinoids are prohibited, and there are specific criteria for those in the hydroxychloroquine expansion cohort regarding medications that affect heart rhythm.

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

Research has shown that a combination of four drugs—paclitaxel protein bound, gemcitabine, cisplatin, and hydroxychloroquine—has been studied for treating pancreatic cancer. One study examined the safety of these drugs when used together. The results indicated that most patients tolerated the treatment well, though some experienced manageable side effects.

The study detailed specific doses: 125 mg/m² of paclitaxel protein bound, 1000 mg/m² of gemcitabine, and 25 mg/m² of cisplatin. These doses were administered over a set period to observe patient reactions. While side effects like nausea or fatigue were reported, they were not severe for most patients.

This treatment is currently in a phase that examines both its effectiveness and safety. Although some safety information is available, more research is needed to fully understand the safety of these drugs when combined. Prospective trial participants should discuss these details with a doctor to understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for pancreatic cancer because it combines Paclitaxel protein bound, Gemcitabine, Cisplatin, and Hydroxychloroquine in a novel way. This combination targets the cancer cells more effectively by using multiple mechanisms of action, potentially improving outcomes compared to standard treatments like Gemcitabine alone or FOLFIRINOX. The inclusion of Hydroxychloroquine is particularly interesting as it may help overcome drug resistance by inhibiting autophagy, a survival mechanism used by cancer cells. This multi-drug approach aims to enhance treatment efficacy and provide new hope for patients facing this challenging disease.

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

Research has shown that a combination of three drugs—paclitaxel protein bound, gemcitabine, and cisplatin—may help treat pancreatic cancer. In earlier studies, this combination effectively controlled the disease in its early stages, reduced tumor size, and improved symptoms for patients. These treatments attack cancer cells, slow their growth, and sometimes shrink the tumors. Given the aggressive and difficult-to-treat nature of pancreatic cancer, this combination offers hope by potentially improving patient outcomes. Early results suggest it might help patients live longer, but more research is needed to confirm these benefits. Participants in this trial will receive this combination along with hydroxychloroquine as part of the treatment regimen. ^{1 4 5 6 7}

Who Is on the Research Team?

Erkut Borazanci, MD

Principal Investigator

HonorHealth Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with non-metastatic pancreatic cancer who haven't had chemotherapy or radiation. They must have a specific tumor marker elevated, normal organ function, and agree to use contraception if sexually active. Excluded are those with certain infections, recent major surgery, allergies to study drugs, lung conditions, heavy cannabinoid use, or other serious health risks.

Inclusion Criteria

My organs and bone marrow are functioning normally.

My blood clotting status is within the safe range.

If a female patient is of child-bearing potential, she must have a negative serum pregnancy test (≥β-hCG) documented within 72 hours of the first administration of study drug

Exclusion Criteria

My cancer has spread to distant parts of my body.

Serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the patient to receive an experimental research drug

I have a history of lung conditions like sarcoidosis or pulmonary fibrosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemotherapy with Paclitaxel Protein Bound, Gemcitabine, Cisplatin, and Hydroxychloroquine

6 months

Follow-up

Participants are monitored for safety, effectiveness, and resectability after treatment

6 months to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Gemcitabine
• Hydroxychloroquine
• Paclitaxel protein bound

Trial Overview The trial tests a combination of Paclitaxel Protein Bound + Gemcitabine + Cisplatin + Hydroxychloroquine in patients with pancreas cancer. It aims to see how this regimen affects the CA 19-9 tumor marker after up to six months before surgery.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 4 Interventions

Paclitaxel Protein Bound + Gemcitabine + Cisplatin + Hydrochloroquine

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

HonorHealth Research Institute

Lead Sponsor

Trials

26

Recruited

940+

Published Research Related to This Trial

In a study of 200 pancreatic cancer patients receiving gemcitabine and nanoparticle albumin-bound paclitaxel, treatment suspension occurred in 61% of cases, primarily due to severe neutropenia (grade 3/4) in 83.6% of patients.

Low baseline platelet counts and age over 65 were identified as risk factors for treatment suspension, while initiating treatment with a dose reduction helped prevent severe neutropenia and allowed for better management of the chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of risk factors related to administration suspension and severe neutropenia in gemcitabine and nab-paclitaxel treatment. Saito, Y., Takekuma, Y., Kobayashi, M., et al.[2022]

In a phase 2 study involving 36 patients with advanced pancreatic cancer, the combination of cisplatin and gemcitabine showed promising activity, with 62.8% of patients achieving stable disease or better, and a median survival of 9.5 months.

While significant hematological toxicities were observed, they were mostly asymptomatic, and the treatment regimen demonstrated potential for improving survival, warranting further investigation in a larger randomized controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of weekly cisplatin and gemcitabine in patients with advanced pancreatic cancer: is this a strategy still worth pursuing? Clayton, AJ., Mansoor, AW., Jones, ET., et al.[2022]

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 and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., et al.[2022]

In a phase III clinical trial involving 42 patients with locally advanced or metastatic pancreatic cancer, both gemcitabine (GEM) alone and GEM combined with cisplatin (CDDP) showed moderate efficacy, with overall response rates of 31.3% for GEM and 27.8% for the combination therapy.

The study demonstrated that GEM or GEM plus CDDP improved the quality of life and prolonged survival times, with 6-month survival rates of 81.3% for GEM and 61.6% for GEM plus CDDP, while maintaining a manageable toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine or gemcitabine plus cisplatin for in 42 patients with locally advanced or metastatic pancreatic cancer. Wang, X., Ni, Q., Jin, M., et al.[2022]

In a study of 58 patients with resectable metastatic pancreatic cancer treated with gemcitabine and docetaxel, the median overall survival was 52 months, with a 5-year survival rate of 49%, indicating a favorable outcome for this treatment approach.

The study found that while 52% of patients experienced significant toxicity (grade 3 or 4), the majority completed their treatment regimen, and the use of chemoradiation after gem/tax was positively associated with improved survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival? Kanji, ZS., Edwards, AM., Mandelson, MT., et al.[2022]

The combination of gemcitabine and low-dose cisplatin shows promising activity in treating metastatic and locally advanced pancreatic cancer, with a median progression-free survival of 4.4 months and median overall survival of 6.7 months based on a study of 58 patients.

While 66% of patients experienced significant toxicities, primarily hematologic, this treatment regimen is considered a viable first-line option for patients who cannot receive standard treatments like gemcitabine plus nab-paclitaxel, especially those with BRCA1 and/or BRCA2 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly gemcitabine and low-dose cisplatin in the treatment of locally advanced or metastatic pancreatic cancer patients: a single institute experience. Lundberg, J., Reardon, J., Blazer, M., et al.[2022]

In a phase II study involving 45 patients with advanced pancreatic cancer, the combination of gemcitabine and cisplatin resulted in a low overall response rate of only 9%, with one complete and four partial responses observed.

Despite some patients experiencing stable disease (46%) and a median survival of 5.6 months, the study concluded that this chemotherapy regimen did not provide a significant advantage in efficacy, and side effects were primarily hematological, with notable toxicities requiring dose reductions in 31% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Cascinu, S., Labianca, R., Catalano, V., et al.[2022]

Bortezomib enhances the effectiveness of gemcitabine in treating pancreatic cancer by altering the gene expression profile of cancer cells, particularly in those with varying sensitivity to gemcitabine, as shown in a study using pancreatic cancer cell lines BxPC-3 and PANC-1.

The study identified 44 genes that were significantly up-regulated by bortezomib, including the repression of the anti-apoptotic gene Bcl-2, suggesting that bortezomib may promote cancer cell death and could be a promising therapeutic target in pancreatic cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the proteasome inhibitor bortezomib on gene expression profiles of pancreatic cancer cells. Tang, ZY., Wu, YL., Gao, SL., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.667

Paclitaxel protein bound (A) plus gemcitabine (G) ... Outcomes of patients with borderline-resectable pancreatic cancer treated with FOLFIRINOX versus gemcitabine plus nab-paclitaxel. Shaina D ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.4631

Paclitaxel protein bound (A) plus gemcitabine (G) ... Outcomes and Immunogenicity of pancreatic cancer stratified by the HRDetect score. Previous · NEXT ARTICLE. Interim data: Phase I/IIa study of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11192994/

Phase II clinical trial of nab‐paclitaxel plus cisplatin plus ... NABPLAGEM has efficacy in advanced PDAC, demonstrating early disease control noted by improvement in patient symptoms, decrease in tumor volume and tumor ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03415854

Paclitaxel Protein Bound Plus Cisplatin Plus Gemcitabine ... Pancreatic cancer continues to be a highly lethal disease with an overall 5 year survival of only 8%. Since 2004, the incidence of pancreatic cancer has ...

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.70035

Advances in pancreatic cancer early diagnosis, prevention ... For the vast majority of patients diagnosed with metastatic PDAC, the 5-year overall survival rate remains below 10%, and two primary systemic ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04669197

Study of Paclitaxel Protein Bound + Gemcitabine ... To evaluate the normalization rate of CA 19-9 of individuals with non-metastatic pancreas cancer following up to 6 months of neoadjuvant chemotherapy. Official ...

7. researchgate.net researchgate.net/publication/377606252_Paclitaxel_protein_bound_A_plus_gemcitabine_G_plus_cisplatin_C_and_hydroxychloroquine_HCQ_neoadjuvant_therapy_for_localized_pancreatic_ductal_adenocarcinoma_PDAC

Paclitaxel protein bound (A) plus gemcitabine (G) ... Paclitaxel protein bound (A) plus gemcitabine (G) plus cisplatin (C) and hydroxychloroquine (HCQ) neoadjuvant therapy for localized pancreatic ductal ...