Combination Chemotherapy + TTF for Pancreatic Cancer

Recruiting at2 trial locations

Overseen by Hani M. Babiker, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Arizona

Must not be taking: Torsades de Pointes drugs

Disqualifiers: Brain metastasis, Heart block, Pacemakers, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for advanced pancreatic cancer using a mix of three chemotherapy drugs and a special device that uses electric fields to target cancer cells. Patients continue with one drug and the electric field device. The goal is to find a more effective front-line therapy for patients whose cancer has spread. The use of electric fields to disrupt cancer cell division is a novel approach that has shown promise in other cancers, such as malignant pleural mesothelioma.

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 prohibit the use of drugs with a black box warning for Torsades de Pointes if they cannot be replaced by another drug. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Combination Chemotherapy + TTF for Pancreatic Cancer?

Research shows that combining nab-paclitaxel (a form of paclitaxel linked to albumin) with gemcitabine has improved survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. This suggests that the combination of these drugs can be effective in treating pancreatic cancer. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs and TTF generally safe for humans?

Research shows that the combination of albumin-bound paclitaxel (nab-paclitaxel) with other chemotherapy drugs like cisplatin and gemcitabine has been studied for safety in various cancers, including lung and pancreatic cancer. These studies indicate that this combination can be effective and generally safe, with reduced adverse reactions compared to traditional chemotherapy regimens. ^{3 6 7 8 9}

What makes the combination chemotherapy with TTF for pancreatic cancer unique?

This treatment is unique because it combines traditional chemotherapy drugs with Tumor Treating Fields (TTF), a novel therapy that uses electric fields to disrupt cancer cell division, potentially enhancing the effectiveness of the chemotherapy. ^{1 2 10 11 12}

Research Team

Hani M. Babiker, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with stage IV metastatic pancreatic cancer who haven't had treatment for advanced disease. They can join if they've had certain previous therapies, but not if they have brain metastasis or heart issues. Participants need functioning major organs and no severe cardiac risks, and women must not be pregnant.

Inclusion Criteria

Laboratory data as specified below:

Patients must have measurable disease on scans per RECIST 1.1

Ability to operate the Novo TTF-100L (P) system

Exclusion Criteria

Patients who are pregnant or breastfeeding

I have cancer that has spread to my brain.

I have received initial treatment for cancer that has spread.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gemcitabine, cisplatin, and protein-bound paclitaxel combined with Tumor Treatment Fields (TTF) for 6 cycles

12 weeks

Every 2 weeks

Maintenance

Participants transition to maintenance therapy with gemcitabine and daily TTF until disease progression

Until progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Cisplatin (Alkylating agents)
• Gemcitabine (Anti-metabolites)
• Nab-Paclitaxel (Alkylating agents)
• TTF (Other)

Trial Overview The study tests a combination of chemotherapy drugs (Protein-bound Paclitaxel, Cisplatin, Gemcitabine) with Tumor Treatment Fields (TTF), followed by maintenance therapy. It's an early-phase trial to see how safe this approach is and how well it works in patients.

Participant Groups

Group I: Modified GCN+TTF treatment Experimental Treatment 1 Intervention

The trial will compose of 2 parts with a total of 40 subjects. The regimen will consist of gemcitabine (G) administered at a dose of 800 mg/m2, cisplatin (C) 30 mg/m2, and protein-bound paclitaxel (N) 150 mg/m2 administered on cycle 1 day 1 and every 2 weeks thereafter and TTF will be administered daily (150kHz 18 hours/day) starting with Cycle 1 Day 1 (dose level 1). After completing 6 cycles, patients will then transition to a maintenance phase of G administered at a dose of 1000 mg/m2 every 2 weeks and daily TTF (150 KHZ 18 hours/day) until progression of disease (POD) per RECIST v1.1. If 6 patients tolerate the dose level of GCN+TTF through the 1st cycle without defined dose limiting toxicities (DLTs) or grade 4 treatment related adverse events (TRAE), the 2nd part of the study (phase Ib portion) will commence. An additional 34 patients will be enrolled in the expansion cohort (phase Ib).

Cisplatin is already approved in Canada, Japan for the following indications:

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?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

Dr. Richard Carmona

University of Arizona

Chief Medical Officer since 2021

MD, University of Arizona

Dr. Evan Unger

University of Arizona

Chief Executive Officer since 2021

PhD in Medical Imaging, University of Arizona

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

NovoCure Ltd.

Industry Sponsor

Trials

64

Recruited

6,100+

Ashley Cordova

NovoCure Ltd.

Chief Executive Officer

Bachelor of Science in Material Engineering from Ben-Gurion University of the Negev, Israel

Uri Weinberg

NovoCure Ltd.

Chief Medical Officer since 2020

MD from an unspecified institution

Findings from Research

A phase I study is being conducted to evaluate the safety and determine the maximum tolerated dose of albumin-bound paclitaxel (ABP) delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal metastases from various cancers.

The study will involve three treatments with ABP, escalating the dose from 35 to 140 mg/m², and will assess not only toxicity but also factors like surgical morbidity and quality of life, aiming to set the stage for future randomized phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. Van De Sande, L., Graversen, M., Hubner, M., 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 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]

Nab-paclitaxel, a nanoparticle formulation of paclitaxel, has improved solubility and pharmacokinetics, leading to slightly better survival rates in pancreatic cancer when combined with gemcitabine compared to gemcitabine alone, as shown in Phase III clinical trials.

Innovative laboratory techniques to manipulate cancer cell cycles may enhance the effectiveness of nab-paclitaxel, potentially allowing it to target more tumor cells effectively, even in treatment-resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound-paclitaxel: a limited improvement under the current therapeutic paradigm of pancreatic cancer. Hoffman, RM., Bouvet, M.[2022]

Nanoparticles show great potential in cancer therapy and diagnosis, but there is a significant gap between experimental research and clinical application, with only a few formulations currently in use.

Notable examples of nanoparticle therapies include nanoparticle-albumin-bound paclitaxel and liposomal irinotecan, both of which are approved for treating pancreatic cancer, demonstrating their efficacy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nanoparticles for cancer therapy]. Löhr, M., van der Wijngaart, W., Fagerberg, B.[2019]

In a trial involving 84 patients with advanced non-small-cell lung cancer, the efficacy of weekly nab-paclitaxel plus cisplatin was found to be similar to that of gemcitabine plus cisplatin, with median progression-free survival of 4.8 months for nab-TP and 5.2 months for GP.

Nab-paclitaxel showed improved overall survival in patients with EGFR mutations (26.7 months) and those with a performance status of 0 (23.5 months) compared to gemcitabine, indicating potential benefits in specific patient subgroups while maintaining comparable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer: A phase II open-label clinical study. Qin, S., Yu, H., Wu, X., et al.[2022]

In a study of 78 patients with non-small cell lung cancer, treatment with nano-albumin paclitaxel combined with cisplatin resulted in a significantly higher disease control rate of 79.49% compared to 38.46% for traditional paclitaxel combined with cisplatin after four treatment cycles.

The nano-albumin regimen also showed a lower incidence of adverse reactions, such as myelosuppression, nausea, vomiting, and hyperglycemia, indicating it is both effective and safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Clinical Efficacy of Nano-Albumin Paclitaxel Treatment for Advanced Cell Lung Cancer. Li, X., Zhang, Y., Zhi, X., et al.[2022]

Nab-paclitaxel has recently been introduced as a first-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC), showing promising improvements in patient outcomes after years of stagnation in treatment options.

The review highlights the unique mechanism of action of nab-paclitaxel, particularly its interaction with albumin and SPARC, which may enhance its efficacy in targeting cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel for metastatic pancreatic cancer: clinical outcomes and potential mechanisms of action. Al-Batran, SE., Geissler, M., Seufferlein, T., et al.[2015]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

Total serum nanoparticles (TSN) loaded with piperlongumine (PL) showed greater cytotoxic effects against pancreatic cancer cells compared to those loaded with paclitaxel (PTX) and standard treatments, indicating a promising new approach for cancer therapy.

The TSN-PL nanoparticles demonstrated significant antitumor efficacy in pancreatic cancer xenograft models, suggesting their potential for effective cancer treatment in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer nanomedicine developed from total human serum: a novel approach for making personalized nanomedicine. Thayath, J., Pavithran, K., Nair, SV., et al.[2021]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

In a small study of 3 patients with metastatic ampullary and duodenal adenocarcinoma who had previously failed standard chemotherapy, treatment with nab-paclitaxel and gemcitabine (with or without cisplatin) resulted in excellent tumor responses and over a year of progression-free survival.

All patients showed significant reductions in tumor markers and have survived for 2-3 years since their diagnosis, suggesting that nab-paclitaxel combined with gemcitabine could be a promising salvage therapy for these difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable response for ampullary and duodenal adenocarcinoma with a nab-paclitaxel plus gemcitabine ± cisplatin combination. Cen, P., Wray, CJ., Zhang, S., et al.[2022]

References

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

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. [2023]

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

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

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

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

4. England pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound-paclitaxel: a limited improvement under the current therapeutic paradigm of pancreatic cancer. [2022]

5. Sweden pubmed.ncbi.nlm.nih.gov

[Nanoparticles for cancer therapy]. [2019]

6. China pubmed.ncbi.nlm.nih.gov

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer: A phase II open-label clinical study. [2022]

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

Analysis of Clinical Efficacy of Nano-Albumin Paclitaxel Treatment for Advanced Cell Lung Cancer. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel for metastatic pancreatic cancer: clinical outcomes and potential mechanisms of action. [2015]

9. Germany pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Cancer nanomedicine developed from total human serum: a novel approach for making personalized nanomedicine. [2021]

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

Treatment of ovarian cancer: current status. [2015]

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

Durable response for ampullary and duodenal adenocarcinoma with a nab-paclitaxel plus gemcitabine ± cisplatin combination. [2022]