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Trial record 1 of 1 for:    NCT01093092
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Calcitriol, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors That Cannot Be Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01093092
First received: March 24, 2010
Last updated: August 25, 2014
Last verified: August 2014

March 24, 2010
August 25, 2014
September 2011
December 2014   (final data collection date for primary outcome measure)
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 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
A standard 3+3 with de-escalation will be used to estimate the MTD.
Maximum tolerated dose (MTD) of oral calcitriol when combined with a standard dose of gemcitabine and cisplatin [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01093092 on ClinicalTrials.gov Archive Site
  • Toxicity of this combination, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
    Tabulated overall or by dose level (as appropriate).
  • 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 [ Time Frame: Days 1-3 of course 1 ] [ Designated as safety issue: No ]
    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.
  • Objective tumor response, described using Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Responses tabulated as appropriate.
  • Toxicity of this combination as assessed by NCI CTCAE version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of calcitriol at the MTD in an expanded cohort of 6 patients [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Clinical activity associated with this regimen in patients with advanced solid tumors [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Calcitriol, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors That Cannot Be Removed By Surgery
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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • Dietary Supplement: calcitriol
    Given PO
    Other Names:
    • 1,25(OH)2-D3
    • 1,25-dihydroxycholecalciferol
    • CALTROL
    • Rocaltrol
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: gemcitabine hydrochloride
    Given IV
    Other Names:
    • dFdC
    • difluorodeoxycytidine hydrochloride
    • gemcitabine
    • Gemzar
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
Experimental: 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.
Interventions:
  • Dietary Supplement: calcitriol
  • Drug: cisplatin
  • Drug: gemcitabine hydrochloride
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
42
Not Provided
December 2014   (final data collection date for primary outcome measure)

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 10^9/1
  • Hemoglobin (Hgb) >= 10g/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 or vitamin D supplementation
  • Thiazide (e.g HCTZ, Hydrochorothiazide) 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
Both
18 Years and older
No
United States
 
NCT01093092
I 163509, NCI-2010-00263, I 163509, P30CA016056
No
Roswell Park Cancer Institute
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Grace Dy Roswell Park Cancer Institute
Roswell Park Cancer Institute
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP