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Calcitriol, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors That Cannot Be Removed by Surgery

11 januari 2016 uppdaterad av: Roswell Park Cancer Institute

A Phase I Clinical Trial of Oral Calcitriol With Fixed Dose of Cisplatin and Gemcitabine in Patients With Advanced Solid Tumors

This phase I trial studies the side effects and best dose of calcitriol when given with cisplatin and gemcitabine hydrochloride in treating patients with advanced solid tumors that cannot be removed by surgery. Drugs used in chemotherapy, such as cisplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Calcitriol may stop the growth of tumor cells by blocking blood flow to the tumor. Calcitriol may also help cisplatin and gemcitabine hydrochloride kill more tumor cells by making them more sensitive to the drug.

Studieöversikt

Detaljerad beskrivning

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of oral calcitriol when combined with a standard dose of gemcitabine (gemcitabine hydrochloride) and cisplatin in a 28-day cycle.

SECONDARY OBJECTIVES:

I. Describe the toxicity of this combination using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

II. Study the pharmacokinetics of calcitriol at the maximum tolerated dose (MTD) in an expanded cohort of 6 patients.

III. Describe the clinical activity associated with this regimen in this advanced solid tumor population.

OUTLINE:

Patients receive calcitriol orally (PO) on days 1, 2, 8, 9, 15 and 16; cisplatin intravenously (IV) over 2 hours on day 2; and gemcitabine hydrochloride IV over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Studietyp

Interventionell

Inskrivning (Faktisk)

14

Fas

  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

    • New York
      • Buffalo, New York, Förenta staterna, 14263
        • Roswell Park Cancer Institute
    • Virginia
      • Charlottesville, Virginia, Förenta staterna, 22903
        • Emily Couric Clinical Cancer Center

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • Patients with a diagnosis of advanced unresectable non-hematological malignancy that has no known standard of care or for which the use of gemcitabine plus cisplatin constitutes a reasonable option
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  • White blood cell (WBC) >= 3.0 x 10^9/L
  • Neutrophils >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Hemoglobin (Hgb) >= 10 g/dL
  • Bilirubin =< institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x institutional ULN unless metastatic to liver in which case AST and ALT should be < 5 x institutional ULN
  • Creatinine =< 1.5 x institutional ULN
  • Corrected calcium =< institutional ULN (corrected calcium = (4- Albumin) x 0.8 + calcium)
  • Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment
  • Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
  • No treatment with investigational agents within 4 weeks prior to study drug administration, except patients receiving targeted therapies such as kinase inhibitors with half-lives < 48 hours may be treated if > 14 days have elapsed after the last dose and related toxicities have recovered to =< grade 1
  • No chemotherapy within 4 weeks prior to study treatment administration; nitrosoureas and mitomycin C are not allowed within 6 weeks prior to initiation of study treatment
  • Palliative radiation, including whole brain radiation therapy (WBRT), is allowed prior to enrollment as long as it is completed > 2 weeks from initiation of study treatment, and provided patient has recovered from treatment toxicities to =< grade 1
  • Patients should be able to take oral medications

Exclusion Criteria:

  • Known hypersensitivity to any of the study drugs involved
  • Brain metastases are excluded unless treated and shown to be controlled more than 1 month from after craniotomy or more than 2 weeks after gamma knife radiosurgery and not associated with central nervous system (CNS) symptoms
  • History of clinically significant hypercalcemia
  • Evidence of nephrectomy
  • History of (within 24 months prior to enrollment) of kidney, ureter, or bladder stones with clinically significant sequelae (e.g. (painless gross hematuria; pain with or without infection; hydronephrosis, etc); patients with otherwise stable non-occluding kidney stones regardless of stone type incidentally found in computed tomography (CT) scans are eligible; patients with prior history of uric acid stones are eligible regardless of time of onset
  • Unwillingness to stop calcium supplementation (during the first cycle of treatment) or vitamin D supplementation throughout the study
  • Thiazide (e.g HCTZ, Hydrochoirthiazide) or digoxin therapy (e.g Lanoxicaps, Lanoxin)
  • Pregnant or nursing female patients.
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the investigator's opinion deems the patient an unsuitable candidate to receive study drug
  • Received an investigational agent within 4 weeks prior to enrollment, except patients receiving targeted therapies such as kinase inhibitors with half-lives < 48 hours may be treated if > 14 days have elapsed after the last dose and related toxicities have recovered to =< grade 1
  • Nut allergy

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Treatment (calcitriol, cisplatin, gemcitabine hydrochloride)
Patients receive calcitriol PO on days 1, 2, 8, 9, 15 and 16; cisplatin IV over 2 hours on day 2; and gemcitabine hydrochloride IV over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Korrelativa studier
Andra namn:
  • farmakologiska studier
Givet IV
Givet IV
Andra namn:
  • dFdCyd
  • dFdC
Givet PO
Andra namn:
  • Rocaltrol
  • 1,25-dihydroxikolekalciferol
  • 1,25(OH)2-D3
  • Calcijex

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
MTD of oral calcitriol when combined with a standard dose of gemcitabine hydrochloride and cisplatin, determined according to incidence of dose-limiting toxicity, graded using the National Cancer Institute (NCI) CTCAE version 4.0
Tidsram: 28 days
A standard 3+3 with de-escalation will be used to estimate the MTD.
28 days

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Toxicity of this combination, graded according to NCI CTCAE version 4.0
Tidsram: Up to 30 days after last dose of study drug
Tabulated overall or by dose level (as appropriate).
Up to 30 days after last dose of study drug
Pharmacokinetic (PK) analyses of calcitriol at the MTD in an expanded cohort of 6 patients, including peak levels, area under the concentration-time curve from time 0-72 hours, terminal half-life, volume of distribution, and total body clearance
Tidsram: Days 1-3 of course 1
PK data will be presented as plots of serum calcitriol concentration over time for each patient. An assessment of whether systemic calcitriol exposure associated with antitumor activity in preclinical models is achieved in these patients will be made.
Days 1-3 of course 1
Objective tumor response, described using Response Evaluation Criteria in Solid Tumors 1.1
Tidsram: Up to 5 years
Responses tabulated as appropriate.
Up to 5 years

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Utredare

  • Huvudutredare: Grace Dy, Roswell Park Cancer Institute

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 september 2011

Primärt slutförande (Faktisk)

1 juni 2015

Avslutad studie (Faktisk)

1 november 2015

Studieregistreringsdatum

Först inskickad

24 mars 2010

Först inskickad som uppfyllde QC-kriterierna

24 mars 2010

Första postat (Uppskatta)

25 mars 2010

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

12 januari 2016

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

11 januari 2016

Senast verifierad

1 januari 2016

Mer information

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