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

This study has been terminated.
(Study terminated due to funding issues)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT01197664
First received: September 2, 2010
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
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
Drug: paricalcitol
Radiation: radiation therapy
Other: laboratory biomarker analysis
Drug: fluorouracil
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Paricalcitol Synergism in Conjunction With Standard-of-Care Chemo-Radiation for Resectable Rectal Cancers

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • Toxicity and tolerability of the paricalcitol regimen, as measured by calcium levels [ Time Frame: Assessed up to surgical resection ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
  • Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol [ Time Frame: At surgical resection ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: August 2010
Study Completion Date: April 2014
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (paricalcitol and chemoradiotherapy)
Patients receive paricalcitol PO daily. Patients also receive standard care chemoradiotherapy with fluorouracil PO.
Drug: paricalcitol
Given PO
Other Name: Zemplar
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Drug: fluorouracil
Given PO
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Active Comparator: Arm II (chemoradiotherapy)
Patients receive standard care chemoradiotherapy as in Arm I.
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Drug: fluorouracil
Given PO
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01197664

Locations
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Principal Investigator: George Yacoub, MD Comprehensive Cancer Center of Wake Forest University
  More Information

No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT01197664     History of Changes
Other Study ID Numbers: CCCWFU 54110, NCI-2011-02409
Study First Received: September 2, 2010
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Cystic, Mucinous, and Serous
Fluorouracil
Ergocalciferols
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamins

ClinicalTrials.gov processed this record on July 31, 2014