A Phase I Dual Dose Escalation Study Of Radiation And Nab-Paclitaxel In Patients With Unresectable And Borderline Resectable Pancreatic Cancer

Study Overview

A Phase I Dual Dose Escalation Study of Radiation and Nab-Paclitaxel in Patients With Unresectable and Borderline Resectable Pancreatic Cancer

The investigators hypothesize that intensification of local therapy will lead to improvements in local control and survival in patients with unresectable and borderline resectable pancreatic cancer. We propose to do this by combining nab-paclitaxel concurrently with dose-escalated radiation therapy. In the first part of this phase I study (sub-trial 1), the nab-paclitaxel dose will be escalated while the radiation dose is held constant at a standardly accepted level. The use of this novel chemoradiotherapy regimen will take advantage of nab-paclitaxel's specific anti-tumor and anti-stromal properties, which may enhance the efficacy of radiation therapy, and thereby improve local control. After the MTD of nab-paclitaxel had been determined, a second arm in sub-trial 1 will evaluate the addition of paricalcitol to nab-paclitaxel concurrently with dose-escalated radiation therapy. In addition, after the MTD of the nab-paclitaxel is reached in sub-trial 1 arm A, in the second part of this study (sub-trial 2), we will administer nab-paclitaxel at the determined MTD concurrently with escalated doses of radiation. We will utilize IMRT or protons to safely deliver high doses of radiation while maximally sparing surrounding normal tissue. Patients will also preferentially have 2-3 fiducial markers placed in or around the tumor for daily localization. Chemotherapy before and/or after chemoradiotherapy may be given as per standard of care. Correlative tissue and serum biomarkers are an important, but optional, part of this study.

N/A

Locally Advanced Unresectable Pancreatic Cancer Treated With Chemoradiotherapy
Borderline Resectable Pancreatic Cancer Treated With Chemoradiotherapy

RADIATION: Radiotherapy
DRUG: Abraxane

UPCC 32213

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-07-31	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-11-06
First Submitted that Met QC Criteria 2014-08-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-11-07
First Posted (ACTUAL) 2014-08-04	Results First Posted N/A	Last Verified 2024-11

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Subtrial 1-Arm A (Dose Level 1 of Abraxane) Determine if it is safe or not (via occurrence of dose limiting toxicities) for patients to receive both Abraxane and radiation therapy.	RADIATION: Radiotherapy DRUG: Abraxane Dose varies within subtrial 1 to determine maximum dose. All patients in subtrial 2 receive 125mg Abraxane
EXPERIMENTAL: Subtrial 1-Arm B (Dose Level 2 of Abraxane: 3+4 enrollment) Determine the maximum dose of Abraxane that is allowable and safe for patients receiving both Abraxane and radiation therapy.	RADIATION: Radiotherapy DRUG: Abraxane Dose varies within subtrial 1 to determine maximum dose. All patients in subtrial 2 receive 125mg Abraxane
EXPERIMENTAL: Subtrial 2- Abraxane 125mg; Borderline get 55cGY, unresectable get 57.5cGY until next escalation	RADIATION: Radiotherapy DRUG: Abraxane Dose varies within subtrial 1 to determine maximum dose. All patients in subtrial 2 receive 125mg Abraxane

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Subtrial 1-Arm A (Dose Level 1 of Abraxane)

Determine if it is safe or not (via occurrence of dose limiting toxicities) for patients to receive both Abraxane and radiation therapy.

RADIATION: Radiotherapy

DRUG: Abraxane

Dose varies within subtrial 1 to determine maximum dose. All patients in subtrial 2 receive 125mg Abraxane

EXPERIMENTAL: Subtrial 1-Arm B (Dose Level 2 of Abraxane: 3+4 enrollment)

Determine the maximum dose of Abraxane that is allowable and safe for patients receiving both Abraxane and radiation therapy.

RADIATION: Radiotherapy

DRUG: Abraxane

Dose varies within subtrial 1 to determine maximum dose. All patients in subtrial 2 receive 125mg Abraxane

EXPERIMENTAL: Subtrial 2- Abraxane 125mg; Borderline get 55cGY, unresectable get 57.5cGY until next escalation

RADIATION: Radiotherapy

DRUG: Abraxane

Dose varies within subtrial 1 to determine maximum dose. All patients in subtrial 2 receive 125mg Abraxane

Primary Outcome Measures	Measure Description	Time Frame
Number of Adverse Events		4 years

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Edgar Ben-Josef, MD

Phone Number: 215-662-6567

Email: Edgar.Ben-Josef@pennmedicine.upenn.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Pathologically confirmed adenocarcinoma of the pancreas.
Unresectable disease or borderline resectable disease assessed by a multidisciplinary panel of pancreas surgeon, medical and radiation oncologist, and a radiologist. Criteria defining unresectable and borderline resectable patients will be based on the NCCN Guidelines (v 1.2014):

Greater than 180 degrees of SMA encasement
Any celiac abutment
Unreconstructible SMV/portal occlusion
Aortic invasion or encasement
Nodal metastases beyond the field of resection Borderline resectable
Venous involvement of the SMV/portal vein demonstrating tumor abutment with impingement and narrowing of the lumen
Encasement of the SMV/portal vein but without encasement of the nearby arteries
Short-segment venous occlusion resulting from either tumor thrombus or encasement with suitable proximal and distal vessel for reconstruction/grafting.
Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to celiac axis
Tumor abutment to SMA but not to exceed greater than 180 degrees of circumferential vessel wall
Age > 18 years.
ECOG performance status of ≤ 1.
Adequate organ function defined as follows: absolute neutrophil count of ≥ 1500/mm3, platelets ≥ 100,000/mm3, serum creatinine ≤ 2 mg/dl, total bilirubin ≤ 3, (with relief of biliary obstruction if present (PTC tube or endobiliary stent) and AST < 5 times the upper limit of normal.
Patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial and for 6 months after the trial.
Patients must be able to provide written informed consent.

Distant metastatic disease.
Prior history of abdominal radiation therapy.
Prior systemic therapy for pancreatic cancer.
Prior or simultaneous malignancy within the past 2 years (other than cutaneous squamous or basal cell carcinoma, melanoma in situ, thyroid carcinoma, or low-risk prostate cancer). In-situ carcinoma is allowed.
Serious uncontrolled concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy.
Treatment with an investigational anti-cancer agent within 4 weeks prior to enrollment into the study.
Pregnant women, women planning to become pregnant and women that are nursing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Edgar Ben-Josef, MD, Abramson Cancer Center at Penn Medicine

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

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Clinical Trial Record