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

NCT01093092 | Terminated Phase 1

• 3 other identifiers: I 163509NCI-2010-00263P30CA016056
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Adult Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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

  A standard 3+3 with de-escalation will be used to estimate the MTD.

  28 days

Secondary Outcomes (3)

• Toxicity of this combination, graded according to NCI CTCAE version 4.0

  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

  Days 1-3 of course 1

• Objective tumor response, described using Response Evaluation Criteria in Solid Tumors 1.1

  Up to 5 years

Study Arms (1)

Treatment (calcitriol, cisplatin, gemcitabine hydrochloride)

EXPERIMENTAL

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; Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Other: Pharmacological Study

Interventions

Calcitriol DIETARY_SUPPLEMENT

Given PO

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

Treatment (calcitriol, cisplatin, gemcitabine hydrochloride)

Cisplatin DRUG

Given IV

Treatment (calcitriol, cisplatin, gemcitabine hydrochloride)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdC, dFdCyd

Treatment (calcitriol, cisplatin, gemcitabine hydrochloride)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (calcitriol, cisplatin, gemcitabine hydrochloride)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Emily Couric Clinical Cancer Center

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Interventions

Calcitriol; Cisplatin; Gemcitabine

Intervention Hierarchy (Ancestors)

Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Grace Dy

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

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: March 24, 2010
• First Posted: March 25, 2010
• Study Start: September 1, 2011
• Primary Completion: June 1, 2015
• Study Completion: November 1, 2015
• Last Updated: January 12, 2016

Record last verified: 2016-01

Locations

US (2)