Calcitriol in Combination With Ketoconazole and Therapeutic Hydrocortisone in Treating Patients With Prostate Cancer

May 15, 2017 updated by: Roswell Park Cancer Institute

A Phase I/II Study of Oral Calcitriol in Combination With Ketoconazole in Androgen Independent Prostate Cancer

This phase I/II trial studies the side effects and best dose of calcitriol when given in combination with ketoconazole and therapeutic hydrocortisone and to see how well it works in treating patients with prostate cancer. Calcitriol may help prostate cancer cells become more like normal cells and grow and spread more slowly. Ketoconazole and therapeutic hydrocortisone may help calcitriol work better by making tumor cells more sensitive to the drug. Giving calcitriol together with ketoconazole and therapeutic hydrocortisone may be a better treatment for prostate cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole (400 mg thrice daily [TID]) + oral hydrocortisone (20 mg AM, 10 mg PM) in men with androgen independent prostate cancer (AIPC). (Phase I) II. To estimate the prostate-specific antigen (PSA) response rate. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate the pharmacokinetics of the phase II dose of oral calcitriol with and without ketoconazole (400 mg TID).

II. Describe any objective tumor responses to the combination of oral calcitriol and ketoconazole and hydrocortisone among patients with measurable disease using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

III. Determine toxicities and tolerability of oral calcitriol combination with daily oral ketoconazole and hydrocortisone.

OUTLINE: This is a phase I, dose-escalation study of calcitriol followed by a phase II study.

PHASE I: Patients receive calcitriol orally (PO) once daily (QD) on days 1-3, 8-10, 15-17, and 22-24. Patients also receive ketoconazole PO TID on days 1-24 and therapeutic hydrocortisone PO twice daily (BID) on days -1 to 24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive calcitriol and therapeutic hydrocortisone as in phase I. Patients also receive ketoconazole PO TID on days 4-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
51

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma consistent clinically with androgen independent prostate cancer
  • Measurable disease with elevated PSA or evaluable disease (PSA elevation will constitute evaluable disease)
  • =< 2 regimens of cytotoxic chemotherapy prior to study entry; retinoids, vitamin D analogues, peroxisome proliferator-activated receptor (PPAR) gamma agonists or antagonists, antiandrogens, progestational agents, estrogens, prostate cancer (PC)-SPES, luteinizing hormone-releasing hormone (LHRH)-analogues, vaccines, cytokines will not be considered "cytotoxics"; patients who have previously received ketoconazole + glucocorticoids will be eligible for this trial
  • Patients who have received antiandrogens or progestational agents as therapy for prostate cancer must discontinue therapy and demonstrate a rising PSA >= 28 days following discontinuation (antiandrogen withdrawal- AAW) (>= 42 days for bicalutamide or nilutamide); patients who receive megestrol acetate as therapy for "hot flashes" at a dose of =< 40 mg per day may continue this therapy during this trial; the dose of the megestrol acetate should not be changed during protocol treatment; patients undergoing androgen deprivation using LHRH analogues must continue such agents or undergo orchiectomy to maintain castrate levels of testosterone
  • Patients must have prostate cancer that is advanced or recurrent and for which standard curative or reliable palliative therapies do not exist or are no longer effective
  • Patients should not have received any chemotherapy or investigational agents for at least 4 weeks before entering the study (6 weeks for nitrosoureas or mitomycin C)
  • Eastern Clinical Oncology Group performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy > 3 months
  • Leukocytes: >= 3,000/ul
  • Hemoglobin: >= 8 g/dl
  • Absolute neutrophil count (ANC): >= 1,500/ul
  • Platelets: >= 75,000/ul
  • Total bilirubin: within normal institutional limit
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): =< 2.5 x institutional upper limit of normal
  • Creatine: =< 2 mg/dL
  • Calcium: not above normal institutional limit
  • Patients should be able to receive oral medications
  • Patients with brain metastases which are stable and have been treated with surgery or irradiation will be eligible for this trial
  • Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform the treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • PHASE II - GROUP B: Progressive disease must have occurred on abiraterone within the prior 12 months and patient has not received treatment with enzalutamide
  • Men of all ethnic groups are eligible for this trial; efforts will be made to include minority groups and all representative ethnicities and races in the community serviced by Roswell Park Cancer Institute (RPCI)

Exclusion Criteria:

  • Known severe hypersensitivity to ketoconazole, calcitriol or any of the excipients of these products
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to calcitriol, ketoconazole, or other agents used in study
  • Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial
  • History of kidney, ureteral, or bladder stones within the last 5 years
  • Heart failure or significant heart disease including significant arrhythmias, myocardial infarction within the last 3 months, unstable angina, documented ejection fraction < 30%, or current digoxin therapy
  • Thiazide therapy within 7 days from entering the study
  • Requirement for concurrent systemic glucocorticoid therapy at greater than physiologic replacement doses
  • Unwillingness to stop calcium supplementation
  • As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) or 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 lit compliance with study requirements
  • Human immunodeficiency virus-positive patients receiving combination anti-retroviral therapy are excluded from the study
  • Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St John's wort, alfentanil, alfuzosin, almotriptan, alprazolam, amiodarone, amitriptyline, amprenavir, aprepitant, aripiprazole, bepridil, bortezomib, bosentan, budesonide, buprenorphine, buspirone, carbamazepine, cilostazol, cisapride, cyclosporine, delavirdine, didanosine, digoxin, disopyramide dofetilide, donepezil, eletriptan, eplerenone, fluticasone, fosamprenavir, galantamine, systemic griseofulvin, indinavir, levobupivacaine, lopinavir, midazolam, mifepristone, modafinil, nateglinide, nefazodone, nelfinavir, oxcarbazepine, pimozide, quetiapine, quinidine, repaglinide, rifabutin, rifampin, rifapentine, ritonavir, saquinavir, sildenafil, sirolimus, tacrolimus, tadalafil, tolterodine, theophyllines, tolterodine, triazolam, valdecoxib, vardenafil, ziprasidone, zonisamide, statins, with the exception of pravastatin (Pravachol) or other "statins" which are not metabolized by or induce cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), calcium channel blockers, Coumadin and macrolides or other agents that will be significantly perturbed in a clinically important way by the P450 inhibitory properties of ketoconazole
  • Concomitant use of proton pump inhibitors or histamine (H)2 blockers
  • Treatment with a non-approved or investigational drug or agent within 30 days before day 1 of trial treatment
  • Any unresolved chronic toxicity greater then Common Terminology Criteria (CTC) grade 2 from previous anticancer therapy
  • Incomplete healing from previous oncologic treatments or other major surgery
  • Inability to swallow oral capsules
  • Patients on digoxin will be excluded from this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment (calcitriol, ketoconazole, hydrocortisone)

PHASE I: Patients receive calcitriol PO QD on days 1-3, 8-10, 15-17, and 22-24. Patients also receive ketoconazole PO TID on days 1-24 and therapeutic hydrocortisone PO BID on days -1 to 24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive calcitriol and therapeutic hydrocortisone as in phase I. Patients also receive ketoconazole PO TID on days 4-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Dietary supplement: Calcitriol
Given PO
Other Names:
  • Rocaltrol
  • 1,25-Dihydroxycholecalciferol
  • 1,25(OH)2-D3
  • Calcijex
Drug: Ketoconazole
Given PO
Other Names:
  • Nizoral
  • Fungarest
  • Fungoral
  • Ketoderm
  • Ketoisdin
  • Orifungal M
  • Panfungol
  • R-41400
  • Xolegel
Drug: Therapeutic Hydrocortisone
Given PO
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Barseb-HC
  • Cetacort
  • Cort-Dome
  • Cortef
  • Cortenema
  • Cortifan
  • Cortisol
  • Cortispray
  • Cortril
  • Dermacort
  • Domolene
  • Eldecort
  • Hautosone
  • Heb-Cort
  • Hydrocortone
  • Hytone
  • Komed-HC
  • Nutracort
  • Proctocort
  • Rectoid
  • HYDROCORTISONE

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Determine the Maximum Tolerated Dose (MTD)
Time Frame: up to 11 years
Determine the maximum tolerated dose (MTD) of oral calcitriol daily x 3 consecutive days a week in combination with oral ketoconazole (400 mg thrice daily [TID]) + oral hydrocortisone (20 mg AM, 10 mg PM)
up to 11 years
PSA Response Rate
Time Frame: Up to 11 years
Patients will be considered evaluable for PSA response if they have at least two post-baseline PSA measurements at least 4 weeks apart, or if they have other evidence of disease progression. A PSA response will be considered a PSA decline of at least 50% must be confirmed by a second PSA value four or more weeks later. The reference PSA for these declines should be a PSA measured within 2 weeks prior to the initiation of therapy.
Up to 11 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of Toxicity Graded According to the National Cancer Institute CTC Version 3.0
Time Frame: Up to 11 years
Count of participants with serious adverse event. Please refer to the adverse event reporting for more detail.
Up to 11 years
Objective Tumor Response, Assessed by RECIST
Time Frame: Up to 11 years
Judged by monthly physical exam and radiographic evaluation. Patients will be considered evaluable for tumor response if they have at least two post-baseline tumor assessments at least 4 weeks apart, received study medication for 8 weeks or if they have evidence of disease progression. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Up to 11 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Roswell Park Cancer Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 27, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 27, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 28, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 14, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • I 68905 (Other Identifier: Roswell Park Cancer Institute)
  • NCI-2011-00129 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • RPCI-I-68905
  • P30CA016056 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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