Nab-Paclitaxel Plus Gemcitabine With Concurrent MR-Guided IMRT in Patients With Locally Advanced Pancreatic Cancer

NCT02283372 | Completed Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 201412038
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A phase I study to evaluate safety of gemcitabine with nab-paclitaxel and concurrent IMRT for locally advanced and borderline resectable pancreatic cancer. The goal of this study is to evaluate if a chemotherapy regimen that provides superior systemic efficacy may be safely delivered and enhance efficacy of tumor directed radiation therapy.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  For the toxicity endpoint purposes of this trial, the patient will be followed from start of treatment until the patient completes 60 days of follow-up from the start of radiation therapy, has a dose-limiting toxicity (DLT), or is lost to follow-up.

  Completion of toxicity follow-up for all patients (up to 32 months)

Secondary Outcomes (6)

• Rate of conversion of patients with locally advanced pancreatic cancer or borderline resectable to resectable

  1 year

• Local control (Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

  1 year

• Progression-free survival (PFS)

  1 year

• Overall survival (OS)

  1 year

• Quality of life as measured by the EORTC QLQ-C30

  3 months after completion of treatment (up to 18 weeks)

Study Arms (1)

nab-Paclitaxel + Gemcitabine + IMRT

EXPERIMENTAL

* Prior to initiation of chemoradiation, patients will undergo 1 full cycle of gemcitabine and nab-paclitaxel on Days 1, 8, and 15 of a 28-day cycle. * Both gemcitabine and nab-paclitaxel will be given intravenously on an outpatient basis during the one-month lead-in period and during Weeks 1 and 2 (and, if enrolled to Dose Level or 2, Weeks 4 and 5) of radiotherapy. There may be up to 21 days between the last dose of lead-in chemotherapy (given on Day 15) and initiation of chemoradiation (inclusive of the week following Day 15, the fourth week of the lead-in cycle (an off-week), and an additional week following that). * Intensity modulated radiation (IMRT) - the prescribed dose will range from 40-67.5 Gy over 15 to 25 fractions.

Drug: nab-Paclitaxel; Drug: Gemcitabine; Radiation: Intensity modulated radiation

Interventions

nab-Paclitaxel DRUG

Also known as: Abraxane, Albumin-bound paclitaxel

nab-Paclitaxel + Gemcitabine + IMRT

Gemcitabine DRUG

Also known as: Gemzar®

nab-Paclitaxel + Gemcitabine + IMRT

Intensity modulated radiation RADIATION

Also known as: IMRT

nab-Paclitaxel + Gemcitabine + IMRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas that is considered unresectable or borderline resectable based on institutional standardized criteria of unresectability or medical inoperability. Patients with and without regional adenopathy are eligible.
• Prior systemic chemotherapy allowed. It is anticipated and suggested that most patients enrolled on study will have received a minimum of approximately 2 months of systemic therapy according to routine institutional practices. The patient must also be felt by the treating medical oncologist and radiation oncologist to be a candidate for treatment with gemcitabine/nab-paclitaxel chemoradiotherapy.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,000/mcl
• Platelets ≥ 100,000/mcl
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x ULN
• AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN
• Serum creatinine ≤ 1.5 mg/dL or calculated CrCL\>60mL/min using Cockcroft and Gault formula
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

You may not qualify if:

• Distant metastatic disease, including known brain metastases.
• History of prior malignancy is acceptable, but prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields is not allowed.
• Currently receiving any other investigational agents.
• Major surgery within 4 weeks prior to first study drug administration.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or nab-paclitaxel or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14 days of study entry.
• Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with gemcitabine and nab-paclitaxel. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Hyun Kim, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2014
• First Posted: November 5, 2014
• Study Start: January 21, 2015
• Primary Completion: May 14, 2018
• Study Completion: April 18, 2019
• Last Updated: June 19, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)