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

NCT00536991 | Terminated Phase 1 Results DMC

• 4 other identifiers: I 68905NCI-2011-00129RPCI-I-68905P30CA016056
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage III Prostate Cancer; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• 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)

  up to 11 years

• 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.

  Up to 11 years

Secondary Outcomes (2)

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

  Up to 11 years

• Objective Tumor Response, Assessed by RECIST

  Up to 11 years

Study Arms (1)

Treatment (calcitriol, ketoconazole, hydrocortisone)

EXPERIMENTAL

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.

Dietary Supplement: Calcitriol; Drug: Ketoconazole; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Therapeutic Hydrocortisone

Interventions

Calcitriol DIETARY_SUPPLEMENT

Given PO

Also known as: 1,25(OH)2-D3, 1,25-Dihydroxycholecalciferol, Calcijex, Rocaltrol

Treatment (calcitriol, ketoconazole, hydrocortisone)

Ketoconazole DRUG

Given PO

Also known as: Fungarest, Fungoral, Ketoderm, Ketoisdin, Nizoral, Orifungal M, Panfungol, R-41400, Xolegel

Treatment (calcitriol, ketoconazole, hydrocortisone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (calcitriol, ketoconazole, hydrocortisone)

Pharmacological Study OTHER

Correlative studies

Treatment (calcitriol, ketoconazole, hydrocortisone)

Therapeutic Hydrocortisone DRUG

Given PO

Also known as: Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort, Cort-Dome, Cortef, Cortenema, Cortifan, Cortisol, Cortispray, Cortril, Dermacort, Domolene, Eldecort, Hautosone, Heb-Cort, HYDROCORTISONE, Hydrocortone, Hytone, Komed-HC, Nutracort, Proctocort, Rectoid

Treatment (calcitriol, ketoconazole, hydrocortisone)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Calcitriol; Ketoconazole; Hydrocortisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnenediones; Pregnenes; Pregnanes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

716-845-2300

Study Officials

• Saby George

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 27, 2007
• First Posted: September 28, 2007
• Study Start: October 1, 2006
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: June 14, 2017
• Results First Posted: May 15, 2017

Record last verified: 2017-05

Locations

US (1)