Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Calcitriol, Cisplatin, and Docetaxel in Treating Patients With Advanced Non-Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Biomarker/Laboratory analysis, Treatment	Temporarily closed	Over 18	NCI	RPCI-I-83706 NCT00470431, I 83706

Objectives

Primary

1. 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)
2. Determine the response in patients treated with this regimen. (Phase II)
3. Determine the toxicity of this regimen in these patients. (Phase II)

Secondary

1. Assess pharmacokinetics of this regimen in these patients. (Phase II)
2. Correlate the pharmacokinetic parameters of systemic calcitriol exposure with single nucleotide polymorphisms of 24-hydroxylase (CYP24), the major vitamin D₃ inactivating enzyme.

Entry Criteria

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

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

Patient Characteristics:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• Platelet count ≥ 100,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• WBC > 3,000/mm³
• 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

Expected Enrollment

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

Outcomes

Tumor response (complete and partial response)

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.

Trial Contact Information

Trial Lead Organizations

Roswell Park Cancer Institute

Grace Dy, MD, Principal investigator		Ph: 507-538-1760; 800-685-6825

Registry Information
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
Trial Start Date		2007-01-18
Trial Completion Date		2011-10-05 (estimated)
Registered in ClinicalTrials.gov		NCT00470431
Date Submitted to PDQ		2007-04-06
Information Last Verified		2009-06-07
NCI Grant/Contract Number		CA16056

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