Official Title: “A Phase I/II Clinical Trial of Intravenous (IV) Calcitriol With Fixed Dose of Cisplatin and Docetaxel in Advanced Non-Small Cell Lung Cancer”

RATIONALE: Calcitriol may help non-small cell lung cancer cells become more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving calcitriol together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of calcitriol when given together with cisplatin and docetaxel and to see how well they work in treating patients with advanced non-small cell lung cancer.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label

Study Primary Completion Date: October 2011

OBJECTIVES:

Primary - Determine the maximum tolerated dose and dose-limiting toxicity of calcitriol when combined with cisplatin and docetaxel in patients with advanced non-small cell lung cancer. (Phase I) - Determine the response in patients treated with this regimen. (Phase II) - Determine the toxicity of this regimen in these patients. (Phase II)

Secondary - Assess pharmacokinetics of this regimen in these patients. (Phase II) - Correlate the pharmacokinetic parameters of systemic calcitriol exposure with single nucleotide polymorphisms of 24-hydroxylase (CYP24), the major vitamin D_3 inactivating enzyme.

OUTLINE: This is an open-label, nonrandomized, phase I, dose-escalation study of calcitriol followed by a phase II study. - Phase I: Patients receive calcitriol IV over 1 hour, docetaxel IV over 1 hour, and cisplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of calcitriol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. - Phase II: Patients receive calcitriol at the MTD determined in phase I, docetaxel, and cisplatin as in phase I. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

All patients undergo blood collection at baseline for CYP24 polymorphism analysis. Patients enrolled in phase II also undergo blood collection at baseline and twice on day 1 for pharmacokinetic studies.

After completion of study treatment, patients are followed for 30 days and then periodically thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: calcitriol
• Drug: cisplatin
• Drug: docetaxel
• Procedure: laboratory biomarker analysis
• Procedure: pharmacological study
• Procedure: polymorphism analysis

Primary Measures

• Tumor response (complete and partial response)
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer
• Stage IIIB disease due to malignant pleural effusions or stage IV disease
• Patients with stage IIIB disease must not be eligible for definitive chemoradiotherapy
• Incurable with other modalities
• Measurable disease (Phase II)
• Treated brain metastases allowed provided the patient is neurologically stable for at least 4 weeks after completion of gamma-knife or whole brain radiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• Platelet count ≥ 100,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• WBC > 3,000/mm^3
• Bilirubin normal
• Creatinine normal or creatinine clearance ≥ 50 mL/min
• SGOT or SGPT ≤ 1.5 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 2 years except for nonmelanoma skin cancer or carcinoma in situ of the cervix
• No evidence of peripheral neuropathy ≥ grade 2
• No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• No known hypersensitivity to vitamin D or cisplatin
• No hypercalcemia (albumin corrected calcium > 10.7 mg/dL)
• No other serious illness or medical condition, including any of the following:
• Uncontrolled cardiac disease requiring treatment
• Unstable angina or congestive heart failure within the past 6 weeks
• New onset crescendo or rest angina
• History of significant neurological or psychiatric disorders (e.g., psychotic disorders, dementia, or seizures)
• Active infection
• No renal or bladder stones within the past 10 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy
• No prior nephrectomy
• At least 1 week since prior palliative radiotherapy
• No prior palliative radiotherapy to > 10% of marrow
• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas) or radiotherapy
• More than 30 days since prior investigational drugs (either on phase I, II, or III trials)
• No prior chemotherapy for stage IV non-small cell lung cancer
• Prior adjuvant therapy allowed
• No concurrent digoxin therapy
• No concurrent phenytoin, barbiturates, rifampin, carbamazepine, phenobarbital, or Hypericum perforatum (St. John's wort)
• No concurrent thiazide, digoxin, or glucocorticoid therapy
• Concurrent dexamethasone as pre-medication allowed
• No concurrent calcium supplementation

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Roswell Park Cancer Institute

Overall Clinical Trial Officials and Contacts

Grace K. Dy, MD Principal Investigator Roswell Park Cancer Institute  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00470431

Study ID Number: CDR0000543415

ClinicalTrials.gov Identifier: NCT00470431

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database