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Paricalcitol, Fluorouracil, and Radiation Therapy in Treating Patients With Rectal Cancer That Can Be Removed in Surgery

Primary Purpose

Mucinous Adenocarcinoma of the Rectum, Stage IIA Rectal Cancer, Stage IIB Rectal Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

paricalcitol

radiation therapy

laboratory biomarker analysis

fluorouracil

About this trial

This is an interventional treatment trial for Mucinous Adenocarcinoma of the Rectum

Eligibility Criteria

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

Inclusion Criteria:

Patients must have histologically confirmed T3-T4 adenocarcinoma of rectal mucosal origin or node positive, with no confirmed distant metastases, and that has been shown to be resectable Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Total bilirubin within normal institutional limits Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Patients must not have deficient levels of Vitamin D, 1, 25 Hydroxy as defined by the institution (this allows patients with normal vitamin D or insufficient vitamin D) Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

No prior pelvic radiation therapy or chemo-radiation to the rectum; no chemo-radiation for any other reason in the last 8 weeks Patients may not be receiving any other investigational agents Patients with a history of or current hypercalcemia may not be enrolled in this study History of allergic reactions attributed to compounds of similar chemical or biologic composition to paricalcitol 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 women and nursing mothers are excluded from this study because the adverse effects on the fetus from chemo radiation Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with these agents; 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

Sites / Locations

Wake Forest University Health Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (paricalcitol and chemoradiotherapy)

Arm II (chemoradiotherapy)

Arm Description

Patients receive paricalcitol PO daily. Patients also receive standard care chemoradiotherapy with fluorouracil PO.

Patients receive standard care chemoradiotherapy as in Arm I.

Outcomes

Primary Outcome Measures

Toxicity and tolerability of the paricalcitol regimen, as measured by calcium levels

Calcium levels will be noted on a weekly basis during chemoradiotherapy and graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Secondary Outcome Measures

Biologic effects of oral paricalcitol with oral fluorouracil chemoradiation on vitamin D receptor staining, MIB-1, caspase 3, p 21, and bax protein expression

Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol

Full Information

NCT ID

NCT01197664

First Posted

September 2, 2010

Last Updated

June 29, 2018

Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01197664

Brief Title

Paricalcitol, Fluorouracil, and Radiation Therapy in Treating Patients With Rectal Cancer That Can Be Removed in Surgery

Official Title

A Pilot Study of Paricalcitol Synergism in Conjunction With Standard-of-Care Chemo-Radiation for Resectable Rectal Cancers

Study Type

Interventional

2. Study Status

Record Verification Date

June 2018

Overall Recruitment Status

Terminated

Why Stopped

Study terminated due to funding issues

Study Start Date

August 2010 (undefined)

Primary Completion Date

July 2012 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This randomized pilot clinical trial studies the side effects of giving paricalcitol together with fluorouracil and radiation therapy in treating patients with rectal cancer that can be removed in surgery. Paricalcitol may help rectal cancer cells become more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill tumor cells. It not yet known if chemotherapy and radiation therapy are more effective with or without paricalcitol in treating rectal cancer

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate toxicity and tolerability of oral paricalcitol at 2 μg/day when co-administered with oral 5-fluorouracil (fluorouracil)-based chemoradiation in patients with histologically confirmed, resectable T3-T4 adenocarcinoma of rectal mucosal origin or node-positive disease with no known distant metastases. SECONDARY OBJECTIVES: I. To study the biologic effects of oral paricalcitol in addition to oral 5-fluorouracil chemoradiation on Vitamin D receptor staining, MIB-1, Caspase 3, P 21, and Bax protein expression in these patients. II. To identify patterns of gene expression in tumor samples of patients who receive chemo radiation with and without Paricalcitol supplementation using gene microarray technology. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive paricalcitol orally (PO) daily. Patients also receive standard care chemoradiotherapy with fluorouracil PO. ARM II: Patients receive standard care chemoradiotherapy as in Arm I. In both arms, treatment continues until surgical resection in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 1 month after surgery.

6. Conditions and Keywords

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

Mucinous Adenocarcinoma of the Rectum, Stage IIA Rectal Cancer, Stage IIB Rectal Cancer, Stage IIC Rectal Cancer, Stage IIIB Rectal Cancer, Stage IIIC Rectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I (paricalcitol and chemoradiotherapy)

Arm Type

Experimental

Arm Description

Patients receive paricalcitol PO daily. Patients also receive standard care chemoradiotherapy with fluorouracil PO.

Arm Title

Arm II (chemoradiotherapy)

Arm Type

Active Comparator

Arm Description

Patients receive standard care chemoradiotherapy as in Arm I.

Intervention Type

Drug

Intervention Name(s)

paricalcitol

Other Intervention Name(s)

Zemplar

Intervention Description

Given PO

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Other Intervention Name(s)

irradiation, radiotherapy, therapy, radiation

Intervention Description

Undergo radiotherapy

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Other Intervention Name(s)

5-fluorouracil, 5-Fluracil, 5-FU

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Toxicity and tolerability of the paricalcitol regimen, as measured by calcium levels

Description

Calcium levels will be noted on a weekly basis during chemoradiotherapy and graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Time Frame

Assessed up to surgical resection

Secondary Outcome Measure Information:

Title

Biologic effects of oral paricalcitol with oral fluorouracil chemoradiation on vitamin D receptor staining, MIB-1, caspase 3, p 21, and bax protein expression

Time Frame

Baseline

Title

Biologic effects of oral paricalcitol with oral fluorouracil chemoradiation on vitamin D receptor staining, MIB-1, caspase 3, p 21, and bax protein expression

Time Frame

Day 14

Title

Biologic effects of oral paricalcitol with oral fluorouracil chemoradiation on vitamin D receptor staining, MIB-1, caspase 3, p 21, and bax protein expression

Time Frame

At surgical resection

Title

Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol

Time Frame

Baseline

Title

Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol

Time Frame

Day 14

Title

Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol

Time Frame

At surgical resection

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have histologically confirmed T3-T4 adenocarcinoma of rectal mucosal origin or node positive, with no confirmed distant metastases, and that has been shown to be resectable Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Total bilirubin within normal institutional limits Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Patients must not have deficient levels of Vitamin D, 1, 25 Hydroxy as defined by the institution (this allows patients with normal vitamin D or insufficient vitamin D) Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: No prior pelvic radiation therapy or chemo-radiation to the rectum; no chemo-radiation for any other reason in the last 8 weeks Patients may not be receiving any other investigational agents Patients with a history of or current hypercalcemia may not be enrolled in this study History of allergic reactions attributed to compounds of similar chemical or biologic composition to paricalcitol 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 women and nursing mothers are excluded from this study because the adverse effects on the fetus from chemo radiation Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with these agents; 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

George Yacoub, MD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wake Forest University Health Sciences

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

12. IPD Sharing Statement

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Paricalcitol, Fluorouracil, and Radiation Therapy in Treating Patients With Rectal Cancer That Can Be Removed in Surgery

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