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

Condition(s) targeted: Advanced Solid Tumors

Intervention: calcitriol (Dietary Supplement); cisplatin (Drug); gemcitabine hydrochloride (Drug); pharmacological study (Other)

Phase: Phase 1

Status: Recruiting

Sponsored by: Roswell Park Cancer Institute

Official(s) and/or principal investigator(s):
Grace K Dy, MD, Principal Investigator, Affiliation: Roswell Park Cancer Institute

Overall contact:
AskRPCI, Phone: 1-877-275-7724, Email: AskRPCI@roswellpark.org

RATIONALE: 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. PURPOSE: This phase I trial is studying the side effects and best dose of calcitriol when given together with cisplatin and gemcitabine hydrochloride in treating patients with advanced solid tumors that cannot be removed by surgery.

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

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum tolerated dose (MTD) of oral calcitriol when combined with a standard dose of gemcitabine and cisplatin

Secondary outcome:

Toxicity of this combination as assessed by NCI CTCAE version 4.0

Pharmacokinetics of calcitriol at the MTD in an expanded cohort of 6 patients

Clinical activity associated with this regimen in patients with advanced solid tumors

Detailed description: PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of oral calcitriol when combined with a standard dose of gemcitabine and cisplatin in a 28-day cycle. SECONDARY OBJECTIVES: I. Describe the toxicity of this combination using CTCAE version 4. 0. II. Study the pharmacokinetics of calcitrio1 at the 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 oral calcitriol 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, 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 ECOG Performance Status of 0-1

- Have the following clinical values:

- WBC ≥ 3. 0 x 10 to the 9th/L and Neutrophils ≥ 1. 5 x 10 to the 9th/L and

platelets ≥ 100 x 10 to the 9th/L and Hgb ≥ 10g/dL

- Bilirubin ≤ institutional upper limit of normal (ULN); AST and ALT < 2. 5 x

institutional ULN unless metastatic to liver in which case AST and AL T 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

- 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 is allowed prior to enrollment as long as it is completed > 4

weeks from initiation of study treatment

- 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 2

months from completion of treatment and not associated with CNS symptoms

- History of hypercalcemia

- Evidence of nephrectomy

- History of (within 24 months prior to enrollment) of kidney, ureter, or bladder

stones or active kidney, ureteral, or bladder stones - with the exception of uric

acid stones

- Unwillingness to stop calcium supplementation or vitamin D supplementation

- Thiazide or digoxin therapy

- 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

- Nut allergy

Inclusion of Women and Minorities

- Both men and women and members of all races and ethnic groups are eligible for this study

AskRPCI, Phone: 1-877-275-7724, Email: AskRPCI@roswellpark.org

Roswell Park Cancer Institute, Buffalo, New York 14263, United States; Recruiting
Grace K. DY, MD, Principal Investigator

Starting date: May 2010
Last updated: November 1, 2012