Mucinous Adenocarcinoma of the RectumPhase 1NCT01197664
Paricalcitol, Fluorouracil, and Radiation Therapy in Treating Patients With Rectal Cancer That Can Be Removed in Surgery
A Phase 1 study testing paricalcitol, radiation therapy and laboratory biomarker analysis in people with Mucinous Adenocarcinoma of the Rectum and Stage IIA Rectal Cancer, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mucinous Adenocarcinoma of the Rectum, Stage IIA Rectal Cancer, Stage IIB Rectal Cancer
- What is being tested?
- paricalcitol, radiation therapy and laboratory biomarker analysis
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to Apr 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: A Pilot Study of Paricalcitol Synergism in Conjunction With Standard-of-Care Chemo-Radiation for Resectable Rectal Cancers
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
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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
- Being tested
- paricalcitol, radiation therapy, laboratory biomarker analysis, fluorouracil
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
paricalcitolDrug
Also called Zemplar
Given PO
radiation therapyRadiation
Also called irradiation, radiotherapy, therapy, radiation
Undergo radiotherapy
laboratory biomarker analysisOther
Correlative studies
fluorouracilDrug
Also called 5-fluorouracil, 5-Fluracil, 5-FU
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (paricalcitol and chemoradiotherapy) | Experimental | Patients receive paricalcitol PO daily. Patients also receive standard care chemoradiotherapy with fluorouracil PO. Receives: 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. Receives: Radiation: radiation therapy; Other: laboratory biomarker analysis; Drug: fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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
Measured: At surgical resection
Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol
Measured: Baseline
Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol
Measured: Day 14
Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol
Measured: At surgical resection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2010 (estimated)
- Study startAug 2010
- Primary completionJul 2012
- Study completionApr 2014
Why it stopped: Study terminated due to funding issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucinous Adenocarcinoma of the RectumStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- George Yacoub, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01197664
- Sponsor's protocol ID
- IRB00013006
- Other IDs
- NCI-2011-02409, CCCWFU 54110
- Status last verified
- Jun 2018
- First submitted
- 2 Sep 2010
- Last updated
- 2 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Paricalcitol Synergism in Conjunction With Standard-of-Care Chemo-Radiation for Resectable Rectal Cancers
- ClinicalTrials.gov ID
- NCT01197664
- Acronym / sponsor ID
- IRB00013006
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to funding issues
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2010
- Primary completion
- Jul 2012 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 9 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (paricalcitol and chemoradiotherapy) | Experimental | Drug: paricalcitol, Radiation: radiation therapy, Other: laboratory biomarker analysis, Drug: fluorouracilPatients receive paricalcitol PO daily. Patients also receive standard care chemoradiotherapy with fluorouracil PO. |
| Arm II (chemoradiotherapy) | Active comparator | Radiation: radiation therapy, Other: laboratory biomarker analysis, Drug: fluorouracilPatients receive standard care chemoradiotherapy as in Arm I. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| paricalcitolAlso: ZemplarGiven PO | Drug | Arm I (paricalcitol and chemoradiotherapy) |
| radiation therapyAlso: irradiation, radiotherapy, therapy, radiationUndergo radiotherapy | Radiation | Arm I (paricalcitol and chemoradiotherapy), Arm II (chemoradiotherapy) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (paricalcitol and chemoradiotherapy), Arm II (chemoradiotherapy) |
| fluorouracilAlso: 5-fluorouracil, 5-Fluracil, 5-FUGiven PO | Drug | Arm I (paricalcitol and chemoradiotherapy), Arm II (chemoradiotherapy) |
Primary outcome
Toxicity and tolerability of the paricalcitol regimen, as measured by calcium levels
Time frame: Assessed up to surgical resection
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.
6 secondary outcomes
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
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
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
Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol
Time frame: Baseline
Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol
Time frame: Day 14
Patterns of gene expression in tumor samples of patients who receive chemoradiation with and without paricalcitol
Time frame: At surgical resection
Results and safety
The study was stopped early (reason given: Study terminated due to funding issues). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George Yacoub, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing paricalcitol, radiation therapy and laboratory biomarker analysis in people with Mucinous Adenocarcinoma of the Rectum and Stage IIA Rectal Cancer, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study terminated due to funding issues). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity and tolerability of the paricalcitol regimen, as measured by calcium levels (time frame: Assessed up to surgical resection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2018.