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 February 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: February 24, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Dietary Supplement: calcitriol
Drug: cisplatin
Drug: gemcitabine hydrochloride
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial of Oral Calcitriol With Fixed Dose of Cisplatin and Gemcitabine in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 42
Study Start Date: September 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01093092

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell K. Park    877-275-7724    ASKRPCI@roswellpark.org   
Principal Investigator: Grace K. Dy         
United States, Virginia
Emily Couric Clinical Cancer Center Not yet recruiting
Charlottesville, Virginia, United States, 22903
Contact: Paula M. Fracasso    434-243-6143    Fracasso@virginia.edu   
Principal Investigator: Paula M. Fracasso         
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Grace Dy Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01093092     History of Changes
Other Study ID Numbers: I 163509, NCI-2010-00263, I 163509, P30CA016056
Study First Received: March 24, 2010
Last Updated: February 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Calcitriol
Dihydroxycholecalciferols
Gemcitabine
Cisplatin
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Antineoplastic Agents
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2014