Chemotherapy + Radiation for Pancreatic Cancer

Overseen By Shagufta Shaheen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Loma Linda University

Disqualifiers: Metastatic disease, Recent malignancy, Infections, others

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: 14

30 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 coordinators or your doctor.

What data supports the effectiveness of the drug combination of nab-paclitaxel and gemcitabine for pancreatic cancer?

Research shows that combining nab-paclitaxel (Abraxane) with gemcitabine has led to higher tumor response and survival rates in patients with advanced pancreatic cancer compared to using gemcitabine alone. ^{1 2 3 4 5}

Is the combination of nab-paclitaxel and gemcitabine safe for treating pancreatic cancer?

The combination of nab-paclitaxel (Abraxane) and gemcitabine has been studied in several trials for pancreatic cancer, showing manageable side effects similar to those reported in the MPACT trial. These studies suggest that the treatment is generally safe for patients, including elderly individuals, with advanced pancreatic cancer. ^{5 6 7 8 9}

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

The combination of Gemcitabine and nab-paclitaxel is unique because it has shown significant improvements in survival rates for patients with advanced pancreatic cancer compared to Gemcitabine alone, making it a standard treatment option. Nab-paclitaxel is an albumin-bound form of paclitaxel, which helps deliver the drug more effectively to the tumor. ^{1 2 10 11 12}

What is the purpose of this trial?

The purpose of this phase 2 research study is to determine whether a combination of chemotherapy drugs plus radiation therapy, given before surgery in resectable pancreactic cancer, can help to increase the chances of surgeons achieving and R0 resection. The chemotherapy drugs used are gemcitabine and nab-paclitaxel. These drugs are both approved by the FDA for use in treating adults with pancreatic adenocarcinoma. The investigational portion of this study is providing the chemotherapy drugs and radiation therapy before surgery. Primary Endpoint, R) resection rate ≥70%. Secondary Endpoints, Disease free survival, Overall survival , Perioperative mortality and morbidity.

Research Team

Naveenraj Solomon, MD

Principal Investigator

Loma Linda University Cancer Center

Eligibility Criteria

This trial is for adults over 18 with confirmed pancreatic adenocarcinoma that hasn't been treated yet. They must have good blood, kidney, and liver function, no serious infections needing IV antibiotics, and tumors that can potentially be removed by surgery. Pregnant or breastfeeding individuals or those with recent other cancers are excluded.

Inclusion Criteria

My diagnosis is pancreatic adenocarcinoma.

My blood, kidney, and liver tests are within the required ranges.

Non-pregnant and non-breast-feeding

Exclusion Criteria

I haven't had any cancer except for minor skin cancers or cancers cured by surgery or surgery plus radiotherapy in the last 5 years.

I do not have any serious infections that need treatment with medication.

My cancer is at a stage where surgery might not remove it all, or it has spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Chemotherapy

Participants receive a combination of Gemcitabine and Nab-paclitaxel for a maximum of four 28-day cycles before surgery

16 weeks

3 visits per cycle (in-person)

Radiation Therapy

Participants receive Stereotactic Body Radiation Therapy (SBRT) with a total dose of 30 Gy

1 week

5 visits (in-person)

Surgery

Participants undergo pancreatic resection surgery

1 day

Post-operative Chemotherapy

Participants receive a combination of Gemcitabine and Nab-paclitaxel for a maximum of two 28-day cycles after surgery

8 weeks

3 visits per cycle (in-person)

Follow-up

Participants are monitored for disease-free survival and overall survival

Up to 6 years

Every 3 months for 2 years, then every 6 months up to 6 years (in-person)

Treatment Details

Interventions

• Gemcitabine
• nab-paclitaxel
• Stereotactic Body Radiation Therapy

Trial Overview The study tests if giving two FDA-approved chemotherapy drugs (gemcitabine and nab-paclitaxel) plus radiation therapy before surgery can improve the chances of completely removing pancreatic cancer. The main goal is to see if this approach leads to a high rate of complete tumor removal without any remaining cancer cells.

Participant Groups

Group I: Chemotherapy and SBRT Experimental Treatment 3 Interventions

Pre-Operative Chemotherapy: Within 28 days of study enrollment, subjects will receive a combination of Gemcitabine and Nab-paclitaxel for a maximum of four 28-day cycles. Gemcitabine 1000 mg/m2 IV on Days 1,8,15. Nab-paclitaxel 125 mg/m2 on Days 1,8,15. Post-Operative Chemotherapy: Within 5-10 weeks after surgery, subjects will receive a combination of Gemcitabine and Nab-paclitaxel for a maximum of two 28-day cycles. Gemcitabine 1000 mg/m2 IV on Days 1,8,15. Nab-paclitaxel 125 mg/m2 on Days 1,8,15. Standard Stereotactic Body Radiation Therapy (SBRT) fractionation of 6 Gy per day will be used for all patients to a total dose of 30 Gy.

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Findings from Research

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 patients with resected pancreatic ductal adenocarcinoma (PDAC), adjuvant chemotherapy with nab-paclitaxel plus gemcitabine (AG) significantly improved median disease-free survival (15.8 months) and overall survival (28.3 months) compared to gemcitabine alone (12.2 months and 20.6 months, respectively).

While AG showed better survival outcomes, it also led to a higher incidence of sensory neuropathy (53.3% in AG vs. 23.3% in GEM), indicating a trade-off between efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. Yin, ZZ., Zhao, ZM., Tang, WB., et al.[2020]

In a phase I trial involving 38 patients with borderline resectable pancreatic cancer, the recommended dose of gemcitabine and nab-paclitaxel for concurrent chemoradiation therapy was established at 800 mg/m² and 100 mg/m², respectively.

The treatment showed a high success rate, with 24 out of 30 patients undergoing surgery and a remarkable R0 resection rate of 96%, indicating effective tumor removal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial Evaluating the Safety of Preoperative Gemcitabine/nab-Paclitaxel With Concurrent Radiation Therapy for Borderline Resectable Pancreatic Cancer. Takahashi, H., Akita, H., Ioka, T., et al.[2022]

The combination of weekly paclitaxel and hyperfractionated radiotherapy at a total dose of 63.80 Gy was found to be tolerable for patients with unresectable pancreatic cancer, with a maximum tolerated dose of paclitaxel identified as 60 mg/m²/week.

The treatment showed promising antitumor activity, with 10 out of 17 assessable patients achieving stable disease or better, and significant pain relief reported in 10 of 14 patients, suggesting potential for further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperfractionated radiotherapy and paclitaxel for locally advanced/unresectable pancreatic cancer. Ashamalla, H., Zaki, B., Mokhtar, B., et al.[2019]

In a phase 1 study involving 9 patients with locally advanced pancreatic cancer, the combination of weekly nab-paclitaxel and daily radiotherapy was found to be safe and well-tolerated, with minimal severe side effects.

After treatment, 4 patients were able to undergo surgical resection with negative margins, indicating a significant treatment effect and limited tumor viability, suggesting potential for improved outcomes in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. Shabason, JE., Chen, J., Apisarnthanarax, S., et al.[2022]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

In a study of 27 elderly Japanese patients (aged ≥ 75) with non-curatively resectable pancreatic cancer, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed a high disease control rate of 92.6%, indicating strong efficacy in managing the disease.

Despite its effectiveness, the treatment was associated with significant adverse effects, including a 51.9% incidence of grade 3 or higher hemotoxicity and a 22% rate of grade ≥ 3 peripheral nerve disorders, highlighting the need for careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. Hasegawa, R., Okuwaki, K., Kida, M., et al.[2022]

A retrospective analysis of 59 patients with advanced refractory pancreatic cancer showed that the combination of nab-paclitaxel and gemcitabine (AG) is active as a second-line or beyond treatment, with 10% achieving a partial response and 47% having stable disease.

The median overall survival was 3.9 months and progression-free survival was 3 months, with toxicity levels similar to those reported in the earlier MPACT trial, indicating that AG has manageable side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. Palacio, S., Hosein, PJ., Reis, I., et al.[2020]

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

In a study of 11 patients with metastatic or recurrent pancreatic cancer, the combination of nab-paclitaxel and gemcitabine showed promising efficacy, with a 6-month overall survival rate of 66.7% and a disease control rate of 90.9%.

The treatment was well tolerated, with no treatment-related deaths and manageable side effects, making nab-paclitaxel plus gemcitabine a potential standard treatment for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. Takeda, Y., Katsura, Y., Ohmura, Y., 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]

The combination of nab-paclitaxel and gemcitabine is an effective first-line treatment for metastatic pancreatic cancer, significantly improving overall survival as demonstrated in the phase III trial (MPACT).

In this case study of a 64-year-old man with recurrent pancreatic cancer, the treatment was generally well-tolerated, although he experienced Grade 3 neutropenia, leading to missed doses; he ultimately passed away 9 months after starting chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A Case of Gemcitabine and Nab-Paclitaxel Therapy for Multiple Metastatic Pancreatic Cancer]. Takashima, Y., Shibamoto, J., Kawamura, Y., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

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

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. [2020]

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

Phase I Trial Evaluating the Safety of Preoperative Gemcitabine/nab-Paclitaxel With Concurrent Radiation Therapy for Borderline Resectable Pancreatic Cancer. [2022]

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

Hyperfractionated radiotherapy and paclitaxel for locally advanced/unresectable pancreatic cancer. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. [2022]

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

nab-Paclitaxel for the treatment of pancreatic cancer. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. [2022]

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

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. [2020]

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

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. [2022]

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

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

12. Japan pubmed.ncbi.nlm.nih.gov

[A Case of Gemcitabine and Nab-Paclitaxel Therapy for Multiple Metastatic Pancreatic Cancer]. [2022]