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

19 Participants Needed

Trial Summary

What is the purpose of this trial?

To evaluate the normalization rate of CA 19-9 of individuals with non-metastatic pancreas cancer following up to 6 months of neoadjuvant chemotherapy.

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.

What data supports the effectiveness of the drug combination used in the chemotherapy for pancreatic cancer trial?

Research shows that the combination of gemcitabine and nab-paclitaxel improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. Additionally, gemcitabine and cisplatin have been used together in trials for advanced pancreatic cancer, showing potential benefits. ^{1 2 3 4 5}

Is the chemotherapy treatment with gemcitabine and cisplatin safe for pancreatic cancer patients?

The combination of gemcitabine and cisplatin has been studied in pancreatic cancer patients and is generally considered to have manageable toxicities, although some patients may experience severe side effects like hematologic toxicity (blood-related issues) and neutropenia (low white blood cell count). ^{6 7 8 9 10}

What makes the chemotherapy treatment for pancreatic cancer unique?

This treatment combines cisplatin, gemcitabine, and paclitaxel protein bound, which is a novel approach as it uses a combination of drugs that have shown potential benefits in other cancers, but their effectiveness in pancreatic cancer is still being explored. The combination aims to improve outcomes by using different mechanisms to attack cancer cells, although previous studies have shown mixed results in terms of effectiveness. ^{2 4 5 9 11}

Research Team

Erkut Borazanci, MD

Principal Investigator

HonorHealth Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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 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 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]

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 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 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 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]

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

Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival? [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. [2022]

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

Phase I/II trial of induction chemotherapy followed by concurrent chemoradiotherapy and surgery for locoregionally advanced pancreatic cancer. [2022]

5. United States 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? [2022]

6. United States 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. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Detection of risk factors related to administration suspension and severe neutropenia in gemcitabine and nab-paclitaxel treatment. [2022]

8. China pubmed.ncbi.nlm.nih.gov

Gemcitabine or gemcitabine plus cisplatin for in 42 patients with locally advanced or metastatic pancreatic cancer. [2022]

9. England 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). [2022]

10. China pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gemcitabine plus S-1 vs. gemcitabine plus nab-paclitaxel in treatment-naïve advanced pancreatic ductal adenocarcinoma. [2023]

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

Effects of the proteasome inhibitor bortezomib on gene expression profiles of pancreatic cancer cells. [2022]