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Prostate AdenocarcinomaPhase 1/2NCT00536991

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

A Phase 1/2 study testing Calcitriol, Ketoconazole and Laboratory Biomarker Analysis in people with Prostate Adenocarcinoma and Recurrent Prostate Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Calcitriol, Ketoconazole and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
1 siteUnited States
Study dates
Oct 2006to Oct 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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)

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Calcitriol, Ketoconazole, Laboratory Biomarker Analysis, Pharmacological Study, Therapeutic Hydrocortisone
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CalcitriolDietary supplement

    Also called 1,25(OH)2-D3, 1,25-Dihydroxycholecalciferol, Calcijex, Rocaltrol

    Given PO

  • KetoconazoleDrug

    Also called Fungarest, Fungoral, Ketoderm, Ketoisdin

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Therapeutic HydrocortisoneDrug

    Also called Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort

    Given PO

Study groups in NCT00536991
Study groupRoleWhat they receive
Treatment (calcitriol, ketoconazole, hydrocortisone)ExperimentalPHASE 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.
Receives: Dietary Supplement: Calcitriol; Drug: Ketoconazole; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Therapeutic Hydrocortisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine the Maximum Tolerated Dose (MTD)

    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)

    Measured: up to 11 years

  2. PSA Response Rate

    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.

    Measured: Up to 11 years

Secondary outcomes (2)

  1. Incidence of Toxicity Graded According to the National Cancer Institute CTC Version 3.0

    Count of participants with serious adverse event. Please refer to the adverse event reporting for more detail.

    Measured: Up to 11 years

  2. Objective Tumor Response, Assessed by RECIST

    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.

    Measured: Up to 11 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2007 (estimated)
  2. Study startOct 2006
  3. Primary completionOct 2016
  4. Study completionOct 2016

Why it stopped: difficult to recruit

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00536991
Sponsor's protocol ID
I 68905
Other IDs
NCI-2011-00129, RPCI-I-68905, I 68905, P30CA016056
Status last verified
May 2017
First submitted
27 Sep 2007
Last updated
14 Jun 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Calcitriol, Ketoconazole and Laboratory Biomarker Analysis in people with Prostate Adenocarcinoma and Recurrent Prostate Carcinoma, run by Roswell Park Cancer Institute 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 22 inclusion and 17 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 14 Jun 2017. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Determine the Maximum Tolerated Dose (MTD) (time frame: up to 11 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00536991.

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 14 Jun 2017.

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