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

Primary Purpose

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

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Radiotherapy

Abraxane

About this trial

This is an interventional treatment trial for Locally Advanced Unresectable Pancreatic Cancer Treated With Chemoradiotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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):

Unresectable

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.

Exclusion Criteria:

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

Sites / Locations

Abramson Cancer Center of the University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

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

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

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

Arm Description

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

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

Outcomes

Primary Outcome Measures

Number of Adverse Events

Secondary Outcome Measures

Full Information

NCT ID

NCT02207465

First Posted

July 31, 2014

Last Updated

January 9, 2023

Sponsor

Abramson Cancer Center at Penn Medicine

1. Study Identification

Unique Protocol Identification Number

NCT02207465

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 2014 (undefined)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Abramson Cancer Center at Penn Medicine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Experimental

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Intervention Type

Drug

Intervention Name(s)

Abraxane

Other Intervention Name(s)

nab-paclitaxel

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Adverse Events

Time Frame

4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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): Unresectable 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. Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Edgar Ben-Josef, MD

Phone

855-216-0098

PennCancerTrials@emergingmed.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edgar Ben-Josef, MD

Organizational Affiliation

Abramson Cancer Center at Penn Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Abramson Cancer Center of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dana Patsch

Phone

215-615-5645

Dana.Patsch@uphs.upenn.edu

First Name & Middle Initial & Last Name & Degree

Edgar Ben-Josef, MD

12. IPD Sharing Statement

Learn more about this trial

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

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