What is the mechanism of action of this treatment?

Gemcitabine, a DNA synthesis inhibitor, interferes with the replication of DNA, preventing cancer cells from multiplying. Nab-paclitaxel, a microtubule inhibitor, disrupts the microtubule structures essential for cell division, leading to cell death. These mechanisms are crucial for pancreatic cancer patients as they target the rapid and uncontrolled cell division characteristic of cancer, potentially improving survival rates and quality of life.

What side effects are associated with this type of intervention?

The combination of gemcitabine and nab-paclitaxel for treating pancreatic cancer is associated with several side effects. Commonly reported grade 3 or 4 toxicities include neutropenia (low white blood cell count), fatigue, neuropathy (nerve damage), and diarrhea. Other side effects may include nausea, thrombocytopenia (low platelet count), and febrile neutropenia (fever with low white blood cell count). These side effects can vary in severity and frequency among patients.

What prior FDA approvals exist?

Gemcitabine, a DNA synthesis inhibitor, was approved by the FDA in 1996 for the treatment of pancreatic cancer. Nab-paclitaxel, a microtubule inhibitor, was later approved in 2013 for use in combination with gemcitabine for the treatment of metastatic pancreatic cancer. This combination has shown improved response rates and survival benefits compared to gemcitabine alone. Other FDA-approved treatments for pancreatic cancer include FOLFIRINOX, a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin, which is used for patients with good performance status.

What other types of research exist?

Promising novel alternatives to Gemcitabine and Nab-Paclitaxel for pancreatic cancer patients include FOLFIRINOX (a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin), which has shown improved survival rates in some patients. Additionally, immunotherapy agents such as pembrolizumab for patients with mismatch repair deficiency and PARP inhibitors for those with BRCA mutations are emerging as potential options. Targeted therapies and combination regimens involving new agents like pegylated irinotecan (Onivyde) are also being explored in clinical trials.

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Anti-metabolites

Gemcitabine/Nab-paclitaxel + Radiation Therapy + Surgical Resection for Pancreatic Cancer

Phase 1 & 2

Waitlist Available

Led By Neesha Dhani, M.D.

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

All Individual Drugs Already Approved

Approved for 10 Other Conditions

No Placebo-Only Group

Summary

This trial tests a combination of cancer treatments and radiation before surgery, followed by additional treatment after surgery. It targets patients with advanced pancreatic cancer affecting major arteries. The treatment aims to shrink the tumor and kill cancer cells before surgery, then continue to eliminate any remaining cancer cells afterward.

Who is the study for?

This trial is for under-70s with advanced pancreatic cancer affecting one major artery, but no metastases or aortic involvement. Candidates must be fit for surgery, not pregnant, agree to contraception use, and have good organ function. Exclusions include HIV/HBV/HCV infection, certain heart diseases, recent major surgery or chemo/radiotherapy to the pancreas within a year.

What is being tested?

The study tests gemcitabine/nab-paclitaxel with radiation therapy before and after surgical removal of the tumor in patients with advanced pancreatic cancer. It aims to determine safety (phase 1) and effectiveness (phase 2) of this combined treatment approach.

What are the potential side effects?

Potential side effects may include reactions from chemotherapy like nausea, fatigue, blood cell count changes leading to increased infection risk; radiation therapy might cause skin irritation or gastrointestinal symptoms; surgery carries risks such as bleeding or infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2012 Phase 3 trial • 256 Patients • NCT01005680

51%

Neutropenia

47%

Leukopenia

46%

Nausea

43%

Vomiting

35%

Anaemia

31%

Decreased appetite

26%

Haemoglobin decreased

26%

Fatigue

25%

Constipation

25%

White blood cell count decreased

24%

Neutrophil count decreased

19%

Alanine aminotransferase increased

13%

Platelet count decreased

12%

Rash

10%

Aspartate aminotransferase increased

10%

Thrombocytopenia

Blood sodium decreased

Hypokalaemia

Insomnia

Pyrexia

Hyponatraemia

Blood creatinine increased

Lymphopenia

Diarrhoea

Dyspepsia

Red blood cell count decreased

Cough

Dizziness

Bone marrow failure

Cerebral infarction

Dyspnoea

Ischaemic stroke

Pulmonary embolism

Embolism venous

Superior vena cava syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Gemcitabine Plus Cisplatin (GC)

Pemetrexed Plus Cisplatin (PC)

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Gemcitabine/Nab-paclitaxel, Radiation and SurgeryExperimental Treatment4 Interventions

Gemcitabine (neoadjuvant and adjuvant), intravenously, at a dose of 1000 mg/m2 given over 30-40 minutes, on Day 1 of every 28 day cycle for 2 cycles. Nab-paclitaxel, intravenously, at a dose of 125 mg/m2 given over 30-40 minutes, on Days 1, 8, and 15 of every 28 day cycle for 2 cycles. Radiation Therapy: 50.4 Gy in 28 fractions (1.8 Gy/fraction) Surgery: Tumor resection and arterial resection/reconstruction

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gemcitabine

FDA approved

Paclitaxel

FDA approved

Radiation Therapy

2017

Completed Phase 3

~7250

Surgical Resection

2018

Completed Phase 2

~420

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Gemcitabine, a DNA synthesis inhibitor, interferes with the replication of DNA, preventing cancer cells from multiplying. Nab-paclitaxel, a microtubule inhibitor, disrupts the microtubule structures essential for cell division, leading to cell death. These mechanisms are crucial for pancreatic cancer patients as they target the rapid and uncontrolled cell division characteristic of cancer, potentially improving survival rates and quality of life.