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

NCT01197664 | Terminated Phase 1 FDA Drug

• 3 other identifiers: IRB00013006NCI-2011-02409CCCWFU 54110
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Assessed up to surgical resection

Secondary Outcomes (6)

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

  Baseline

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

  Day 14

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

  At surgical resection

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

  Baseline

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

  Day 14

Study Arms (2)

Arm I (paricalcitol and chemoradiotherapy)

EXPERIMENTAL

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

Drug: paricalcitol; Radiation: radiation therapy; Other: laboratory biomarker analysis; Drug: fluorouracil

Arm II (chemoradiotherapy)

ACTIVE COMPARATOR

Patients receive standard care chemoradiotherapy as in Arm I.

Radiation: radiation therapy; Other: laboratory biomarker analysis; Drug: fluorouracil

Interventions

paricalcitol DRUG

Given PO

Also known as: Zemplar

Arm I (paricalcitol and chemoradiotherapy)

radiation therapy RADIATION

Undergo radiotherapy

Also known as: irradiation, radiotherapy, therapy, radiation

Arm I (paricalcitol and chemoradiotherapy); Arm II (chemoradiotherapy)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (paricalcitol and chemoradiotherapy); Arm II (chemoradiotherapy)

fluorouracil DRUG

Given PO

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Arm I (paricalcitol and chemoradiotherapy); Arm II (chemoradiotherapy)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

paricalcitol; Radiotherapy; Radiation; Fluorouracil

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• George Yacoub, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 2, 2010
• First Posted: September 9, 2010
• Study Start: August 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: April 1, 2014
• Last Updated: July 2, 2018

Record last verified: 2018-06

Locations

US (1)