Phase I/II Study of High-Dose Calcitriol Plus Temodar for Patients With Metastatic Melanoma

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00301067
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 20
• Location: 1
• Arms: 4
• Actual Duration (Months): 89.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Calcitriol may help temozolomide kill more tumor cells by making them more sensitive to the drug. Calcitriol may also stop the growth of melanoma by blocking blood flow to the tumor.

PURPOSE: This phase I/II trial is studying the best dose of calcitriol, the side effects of calcitriol when given together with temozolomide, and to see how well they work in treating patients with metastatic stage IV melanoma.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Melanoma	Dietary Supplement: Calcitriol; Drug: Temozolomide	Phase 1/Phase 2

Detailed Description

• Phase I: Patients receive oral calcitriol on days 1 and 15 and oral temozolomide on days 2-8 and 16-22. Treatment repeats every 28 days for 2 courses in the absence of unacceptable toxicity. Responding patients continue therapy for up to 6 courses in the absence of 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 temozolomide and calcitriol at the MTD as in phase I.

After completion of study treatment, patients are followed every 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: 3+3 dose escalation design study. (3) patients per dose stratum will be entered in the following cohorts: Cohort 1 - Temozolomide and Calcitriol 0.2mcg/kg days 1 + 15 Cohort 2 - Temozolomide and Calcitriol 0.3 mcg/kg days 1 + 15 Cohort 3 - Temozolomide and Calcitriol 0.5 mcg/kg days 1 + 15 Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every 28 day cycle in each cohort. If 1 patient experiences dose limiting toxicity (DLT) at any dose, that cohort will be expanded to 6 patients. If 2 patients experience DLT in that cohort, further dose escalation will cease and the cohort immediately preceding that cohort will be considered the maximum tolerated dose (MTD). Alternatively, if no more patients experience DLT, then dose will be escalated to the next cohort.3+3 dose escalation design study. (3) patients per dose stratum will be entered in the following cohorts: Cohort 1 - Temozolomide and Calcitriol 0.2mcg/kg days 1 + 15 Cohort 2 - Temozolomide and Calcitriol 0.3 mcg/kg days 1 + 15 Cohort 3 - Temozolomide and Calcitriol 0.5 mcg/kg days 1 + 15 Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every 28 day cycle in each cohort. If 1 patient experiences dose limiting toxicity (DLT) at any dose, that cohort will be expanded to 6 patients. If 2 patients experience DLT in that cohort, further dose escalation will cease and the cohort immediately preceding that cohort will be considered the maximum tolerated dose (MTD). Alternatively, if no more patients experience DLT, then dose will be escalated to the next cohort.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of High-Dose Calcitriol in Combination With Temozolomide for Patients With Metastatic Melanoma
• Actual Study Start Date: Jan 30, 2005
• Actual Primary Completion Date: Apr 5, 2012
• Actual Study Completion Date: Jul 9, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 - Temozolomide and Calcitriol Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days.	Dietary Supplement: Calcitriol; The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle; Drug: Temozolomide; The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Experimental: Cohort 2 - Temozolomide and Calcitriol Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.3 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days.	Dietary Supplement: Calcitriol; The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle; Drug: Temozolomide; The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Experimental: Cohort 3 - Temozolomide and Calcitriol Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days.	Dietary Supplement: Calcitriol; The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle; Drug: Temozolomide; The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Experimental: Expansion - Temozolomide and Calcitriol Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days.	Dietary Supplement: Calcitriol; The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle; Drug: Temozolomide; The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle

Outcome Measures

Primary Outcome Measures

1. Number and Frequency of Dose Limiting Toxicities (DLTs) With High-dose Calcitriol in Combination With Temozolomide [From start of treatment, up to 12 cycles where 1 cycle equals 28 days]

   Determine number and frequency of dose limiting toxicities (DLT) of high-dose calcitriol when administered with temozolomide in patients with metastatic melanoma for up to 12 cycles of therapy, where 1 cycle equals 28 days. 3 patients per dose cohort will be entered into the trial at doses of 0.2, 0.3, and 0.5 mcg/kg of calcitriol administered orally. If 1 patient experiences dose limiting toxicity (DLT) at any dose, that dose cohort will be expanded to a maximum of 6 patients. If 1 additional patient experiences DLT at that dose stratum, further dose escalation will cease and the dose cohort immediately preceding the dose cohort where the 2 experiences of DLT occurred will be considered the MTD. If no additional patients experience DLT, dose escalation to the next higher dose stratum will take place. DLT is defined as National Cancer Institute Common Toxicity Criteria, version 3.0 grade 3 toxicity determined to be related to calcitriol.

2. Number of Patients With Toxicity [From the start of treatment and every 2 weeks for a maximum of 12 cycles, and 30 days post last treatment, where 1 cycle equals 28 days]

   Toxicity will be assessed for each patient on a seven-day on/seven-day off temozolomide in combination with high-dose calcitriol for every 2 weeks for up to 12 cycles where 1 cycle equals 28 days. Toxicity will be assessed during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) and defined by any toxicity determined to be at least possibly related to either study drug (temozolomide or calcitriol). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE Grade 3 and grade 4 toxicities where relatedness to either study drug could not be ruled out were collected and recorded only.

Secondary Outcome Measures

1. Tumor Response [At baseline and every 8 weeks during treatment for a maximum of 12 cycles where one cycle equals 28 days.]

   Determine best tumor response during treatment. Response and progression was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). The same method of assessment and the same technique should be used to characterize each identified and reported lesion at baseline and during follow-up. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

2. The Relationship Between Vitamin D-receptor Gene Polymorphisms and Tumor Response [Baseline and at disease progression or when patient goes off study up to a maximum of 12 months]

   Investigate the relationship between vitamin D-receptor (VDR) gene polymorphisms in Taq1 and Fok1 (analyzed from baseline blood sample) and tumor response. VDR gene analysis was completed using PCR-RFLP based assays.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed malignant melanoma

• Any primary tumor site

• Stage IV disease

• CNS metastases allowed

• Measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension as ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• Must have had at least 1 prior systemic therapy

• Negative pregnancy test

• Fertile patients must use effective contraception

• Patients with no prior systemic therapy are eligible provided they are not candidates for high-dose interleukin-2

• Recovered from all toxic effects of prior therapy

• More than 4 weeks since prior and no concurrent radiotherapy, chemotherapy, or immunotherapy

• More than 4 weeks since prior and no concurrent radiotherapy, chemotherapy, or immunotherapy

• Fertile patients must use effective contraception

Exclusion Criteria:

• Life expectancy less than 4 months

• known HIV positivity

• evidence of active infection requiring antibiotic therapy

• other malignancy within the past 5 years except surgically resected basal cell or squamous cell skin cancer

• significant medical disease which, in the opinion of the investigator, may interfere with study completion

• pregnant or nursing

• Negative pregnancy test

• prior temozolomide or dacarbazine

• investigational agent within 4 weeks prior to study entry

• concurrent magnesium-containing antacids, digitalis, bile-resin binding drugs, or calcium supplements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013

Sponsors and Collaborators

• Northwestern University
• National Cancer Institute (NCI)

Investigators

• Study Chair: Timothy M. Kuzel, MD, Robert H. Lurie Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT00301067
• Other Study ID Numbers: NU 05M1; P30CA060553; NU-05M1; NU-0310-093; SPRI-NU-05M1
• First Posted: Mar 10, 2006
• Last Update Posted: Jun 4, 2019
• Last Verified: May 1, 2019

• Keywords provided by Northwestern University: stage IV melanoma; recurrent melanoma
• Additional relevant MeSH terms: Melanoma; Calcitriol; Temozolomide

Study Results

Participant Flow

Recruitment Details	The study opened for accrual on January 13, 2005 with an accrual goal of between 19-28 patients. Accrual was suspended on March 22 2007, reopening May 7 2007, suspended again January 4, 2008, reopening February 14 2008 both times for toxicity evaluations. The study closed permanently on October 28, 2011 with 20 patients enrolled on the study.

Arm/Group Title	Cohort 1 - Temozolomide and Calcitriol	Cohort 2 - Temozolomide and Calcitriol	Cohort 3 - Temozolomide and Calcitriol	Expansion - Temozolomide and Calcitriol
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.3 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Period Title: Completed DLT Period/1st Cycle
STARTED	4	3	3	10
COMPLETED	3	3	3	9
NOT COMPLETED	1	0	0	1
Period Title: Completed DLT Period/1st Cycle
STARTED	3	3	3	9
COMPLETED	1	2	2	7
NOT COMPLETED	2	1	1	2
Period Title: Completed DLT Period/1st Cycle
STARTED	1	2	2	7
COMPLETED	0	1	0	2
NOT COMPLETED	1	1	2	5
Period Title: Completed DLT Period/1st Cycle
STARTED	0	1	0	2
COMPLETED	0	0	0	0
NOT COMPLETED	0	1	0	2
Period Title: Completed DLT Period/1st Cycle
STARTED	4	3	3	3
COMPLETED	3	3	3	2
NOT COMPLETED	1	0	0	1

Baseline Characteristics

Arm/Group Title	Temozolomide and Calcitriol (Cohort 1-3+Expansion)
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2, 0.3, or 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 55%
>=65 years	9 45%
Sex: Female, Male (Count of Participants)
Female	5 25%
Male	15 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	20 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	20 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Number and Frequency of Dose Limiting Toxicities (DLTs) With High-dose Calcitriol in Combination With Temozolomide
Description	Determine number and frequency of dose limiting toxicities (DLT) of high-dose calcitriol when administered with temozolomide in patients with metastatic melanoma for up to 12 cycles of therapy, where 1 cycle equals 28 days. 3 patients per dose cohort will be entered into the trial at doses of 0.2, 0.3, and 0.5 mcg/kg of calcitriol administered orally. If 1 patient experiences dose limiting toxicity (DLT) at any dose, that dose cohort will be expanded to a maximum of 6 patients. If 1 additional patient experiences DLT at that dose stratum, further dose escalation will cease and the dose cohort immediately preceding the dose cohort where the 2 experiences of DLT occurred will be considered the MTD. If no additional patients experience DLT, dose escalation to the next higher dose stratum will take place. DLT is defined as National Cancer Institute Common Toxicity Criteria, version 3.0 grade 3 toxicity determined to be related to calcitriol.
Time Frame	From start of treatment, up to 12 cycles where 1 cycle equals 28 days

Outcome Measure Data

Analysis Population Description

1 patient enrolled in cohort 1 was not evaluable for this outcome measure as the patient only received 8 days of treatment. Patients enrolled in the expansion cohort were not evaluable for this outcome measure.

Arm/Group Title	Cohort 1 - Temozolomide and Calcitriol	Cohort 2 - Temozolomide and Calcitriol	Cohort 3 - Temozolomide and Calcitriol
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.3 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Measure Participants	3	3	3
Number [DLT]	0	0	0

2. Primary Outcome

Title	Number of Patients With Toxicity
Description	Toxicity will be assessed for each patient on a seven-day on/seven-day off temozolomide in combination with high-dose calcitriol for every 2 weeks for up to 12 cycles where 1 cycle equals 28 days. Toxicity will be assessed during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) and defined by any toxicity determined to be at least possibly related to either study drug (temozolomide or calcitriol). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE Grade 3 and grade 4 toxicities where relatedness to either study drug could not be ruled out were collected and recorded only.
Time Frame	From the start of treatment and every 2 weeks for a maximum of 12 cycles, and 30 days post last treatment, where 1 cycle equals 28 days

Outcome Measure Data

Analysis Population Description

All patients that receive one dose of study drug were evaluable for this outcome measure.

Arm/Group Title	Cohort 1 - Temozolomide and Calcitriol	Cohort 2 - Temozolomide and Calcitriol	Cohort 3 - Temozolomide and Calcitriol	Expansion - Temozolomide and Calcitriol
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.3 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Measure Participants	4	3	3	9
Thrombocytopenia	1 5%	0 NaN	0 NaN	1 NaN
Vascular	1 5%	0 NaN	0 NaN	1 NaN
Nausea	0 0%	0 NaN	1 NaN	0 NaN
Vomiting	0 0%	0 NaN	1 NaN	0 NaN
Leukopenia	0 0%	0 NaN	1 NaN	1 NaN
Fatigue	0 0%	0 NaN	0 NaN	1 NaN
Anemia	0 0%	0 NaN	0 NaN	2 NaN
Lymphopenia	0 0%	0 NaN	0 NaN	2 NaN
Hemorrhage	0 0%	0 NaN	0 NaN	1 NaN
Rash	0 0%	0 NaN	0 NaN	1 NaN
Anorexia	0 0%	0 NaN	0 NaN	1 NaN

3. Secondary Outcome

Title	Tumor Response
Description	Determine best tumor response during treatment. Response and progression was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). The same method of assessment and the same technique should be used to characterize each identified and reported lesion at baseline and during follow-up. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame	At baseline and every 8 weeks during treatment for a maximum of 12 cycles where one cycle equals 28 days.

Outcome Measure Data

Analysis Population Description

Cohort results for this outcome measure are combined as the objective was to determine the tumor response of patients with this drug combination (dose was irrelevant)

Arm/Group Title	Temozolomide and Calcitriol (Cohort 1-3+Expansion)
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2, 0.3, or 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Measure Participants	20
Complete Response	0 0%
Partial Response	2 10%
Stable Disease	1 5%
Progressive Disease	17 85%

4. Secondary Outcome

Title	The Relationship Between Vitamin D-receptor Gene Polymorphisms and Tumor Response
Description	Investigate the relationship between vitamin D-receptor (VDR) gene polymorphisms in Taq1 and Fok1 (analyzed from baseline blood sample) and tumor response. VDR gene analysis was completed using PCR-RFLP based assays.
Time Frame	Baseline and at disease progression or when patient goes off study up to a maximum of 12 months

Outcome Measure Data

Analysis Population Description

Cohort results for this outcome measure are combined as the objective was to investigate relationship of VDR gene polymorphisms present and tumor response of patients with this drug combination (dose was irrelevant) Data was not collected or analyzed for this outcome measure.

Arm/Group Title	Temozolomide and Calcitriol (Cohort 1-3+Expansion)
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2, 0.3, or 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Measure Participants	0

5. Post-Hoc Outcome

Title	Overall Response Rate
Description	Overall Response Rate (ORR) is defined as percentage of patients who's best response to treatment is complete response plus those with partial response. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time Frame	From the start of treatment, every 2 cycles where 1 cycle equals 28 days, for a maximum of 12 cycles

Outcome Measure Data

Analysis Population Description

Cohort results for this outcome measure are combined as the objective was to determine the ORR of patients with this drug combination (dose was irrelevant)

Arm/Group Title	Temozolomide and Calcitriol (Cohort 1-3+Expansion)
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2, 0.3, or 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Measure Participants	20
Count of Participants [Participants]	2 10%

6. Post-Hoc Outcome

Title	Time to Progression
Description	Time to progression (TTP) is measured from the start of treatment until the time of first documentation of disease progression.
Time Frame	From the start of treatment, until progressive disease, up to 12 months

Outcome Measure Data

Analysis Population Description

Cohort results for this outcome measure are combined as the objective was to determine the TTP for patients with this drug combination (dose was irrelevant)

Arm/Group Title	Temozolomide and Calcitriol (Cohort 1-3+Expansion)
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2, 0.3, or 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Measure Participants	20
Median (Inter-Quartile Range) [Months]	1.81

7. Post-Hoc Outcome

Title	Overall Survival
Description	Overall Survival (OS) will be measured from first day of treatment until death of any cause. Patients still alive at the last data cut off point will be censored.
Time Frame	From the first day of treatment until death from any cause, up to a maximum of 6 and half years

Outcome Measure Data

Analysis Population Description

Cohort results for this outcome measure are combined as the objective was to determine the OS of patients with this drug combination (dose was irrelevant)

Arm/Group Title	Temozolomide and Calcitriol (Cohort 1-3+Expansion)
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2, 0.3, or 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Measure Participants	20
Median (Inter-Quartile Range) [Months]	5.5

8. Post-Hoc Outcome

Title	Overall Survival (OS) Stratified by Vitamin D-Receptor (VDR) Gene Polymorphisms
Description	Investigate the relationship between vitamin D-receptor (VDR) gene polymorphisms in Taq1 and Fok1 (analyzed from baseline blood sample) and Overall Survival (OS). VDR gene analysis was completed using PCR-RFLP based assays.
Time Frame	at baseline and until death from any cause up to 6 and half years

Outcome Measure Data

Analysis Population Description

Cohort results for this outcome measure are combined as the objective was to determine the relationship between VDR gene polymorphisms and OS for patients with this drug combination (dose was irrelevant)

Arm/Group Title	Temozolomide and Calcitriol (Cohort 1-3+Expansion)
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2, 0.3, or 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
Measure Participants	17
VDR genotype (tt+/-ff)	3.8
non tt+/-ff VDR genotype	7.4

Adverse Events

Time Frame	Adverse events for the study were collected over a 6 year and 3 month period. For each patient adverse events were collected for a maximum of 12 cycles where 1 cycle equals 28 days.
Arm/Group Title	Cohort 1 - Temozolomide and Calcitriol		Cohort 2 - Temozolomide and Calcitriol		Cohort 3 - Temozolomide and Calcitriol		Expansion - Temozolomide and Calcitriol
Arm/Group Description	Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.2 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle		Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.3 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle		Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle		Temozolomide dose of 150 mg/m2 will be administered orally on days 2-8 and 16-22 every cycle where 1 cycle equals 28 days. Calcitriol dose of 0.5 mcg/kg will be administered orally on days 1 and 15 every cycle where 1 cycle equals 28 days. Calcitriol: The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle Temozolomide: The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
All Cause Mortality
	Cohort 1 - Temozolomide and Calcitriol		Cohort 2 - Temozolomide and Calcitriol		Cohort 3 - Temozolomide and Calcitriol		Expansion - Temozolomide and Calcitriol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		3/3 (100%)		3/3 (100%)		9/10 (90%)
Serious Adverse Events
	Cohort 1 - Temozolomide and Calcitriol		Cohort 2 - Temozolomide and Calcitriol		Cohort 3 - Temozolomide and Calcitriol		Expansion - Temozolomide and Calcitriol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		1/3 (33.3%)		2/3 (66.7%)		4/10 (40%)
Blood and lymphatic system disorders
Thrombocytopenia	0/4 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Gastrointestinal disorders
Nausea and vomiting	0/4 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	0/4 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rapidly declining performance status	0/4 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/10 (0%)	0
Death related to disease	0/4 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/10 (0%)	0
Nervous system disorders
Confusion	1/4 (25%)	1	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0
Slurred speech and drooling	0/4 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/4 (25%)	1	0/3 (0%)	0	0/3 (0%)	0	0/10 (0%)	0
Pulmonary embolus	0/4 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Rash	0/4 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Cohort 1 - Temozolomide and Calcitriol		Cohort 2 - Temozolomide and Calcitriol		Cohort 3 - Temozolomide and Calcitriol		Expansion - Temozolomide and Calcitriol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		3/3 (100%)		3/3 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Anemia (Hemoglobin decrease)	2/4 (50%)		2/3 (66.7%)		2/3 (66.7%)		6/10 (60%)
Neutrophils decreased	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		1/10 (10%)
Leukocytes (white blood count)	0/4 (0%)		0/3 (0%)		2/3 (66.7%)		3/10 (30%)
Lymphopenia	0/4 (0%)		0/3 (0%)		0/3 (0%)		2/10 (20%)
Platelets decreased (thrombocytopenia)	2/4 (50%)		0/3 (0%)		1/3 (33.3%)		2/10 (20%)
Limb edema	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		1/10 (10%)
Edema in head and neck	0/4 (0%)		1/3 (33.3%)		0/3 (0%)		0/10 (0%)
Cardiac disorders
Hypotension	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		0/10 (0%)
Tachycardia	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		0/10 (0%)
Eye disorders
Vision changes	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Gastrointestinal disorders
Anorexia	0/4 (0%)		2/3 (66.7%)		2/3 (66.7%)		5/10 (50%)
Constipation	2/4 (50%)		2/3 (66.7%)		1/3 (33.3%)		5/10 (50%)
Dehydration	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		1/10 (10%)
Diarrhea	0/4 (0%)		1/3 (33.3%)		1/3 (33.3%)		1/10 (10%)
Nausea	4/4 (100%)		2/3 (66.7%)		1/3 (33.3%)		9/10 (90%)
Vomiting	2/4 (50%)		1/3 (33.3%)		1/3 (33.3%)		9/10 (90%)
Blood in stool	0/4 (0%)		1/3 (33.3%)		0/3 (0%)		0/10 (0%)
Hemorrhage CNS	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Abdominal pain - NOS	0/4 (0%)		1/3 (33.3%)		0/3 (0%)		0/10 (0%)
General disorders
Fatigue	0/4 (0%)		2/3 (66.7%)		2/3 (66.7%)		6/10 (60%)
Fever	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		1/10 (10%)
Sweating	1/4 (25%)		0/3 (0%)		1/3 (33.3%)		0/10 (0%)
Weight loss	0/4 (0%)		0/3 (0%)		0/3 (0%)		5/10 (50%)
Weight gain	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		0/10 (0%)
Pain not otherwise specified	1/4 (25%)		2/3 (66.7%)		0/3 (0%)		1/10 (10%)
Infections and infestations
Urinary tract infection NOS	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		2/10 (20%)
Oral infection	0/4 (0%)		0/3 (0%)		0/3 (0%)		2/10 (20%)
Skin infection	1/4 (25%)		0/3 (0%)		0/3 (0%)		0/10 (0%)
Conjunctivitis	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Metabolism and nutrition disorders
Albumin, serum-low	0/4 (0%)		0/3 (0%)		0/3 (0%)		2/10 (20%)
Alkaline phosphatase	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Transaminase	0/4 (0%)		0/3 (0%)		0/3 (0%)		3/10 (30%)
Bicarbonate - low	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Bilirubin, serum high	0/4 (0%)		0/3 (0%)		0/3 (0%)		2/10 (20%)
Calcium, serum low	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Creatinine - high	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Glucose, serum high	0/4 (0%)		0/3 (0%)		0/3 (0%)		2/10 (20%)
Lactic acid dehydrogenase (LDH) increase	0/4 (0%)		0/3 (0%)		0/3 (0%)		2/10 (20%)
Sodium, serum low	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
Back pain	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Chest pain	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		0/10 (0%)
Joint pain	1/4 (25%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Neck pain	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	0/4 (0%)		0/3 (0%)		2/3 (66.7%)		1/10 (10%)
Nervous system disorders
Confusion	0/4 (0%)		0/3 (0%)		0/3 (0%)		2/10 (20%)
Memory impairment	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Motor Neuropathy	1/4 (25%)		0/3 (0%)		0/3 (0%)		2/10 (20%)
Motor Neuropathy - Foot drop	1/4 (25%)		0/3 (0%)		0/3 (0%)		0/10 (0%)
Lightheadedness	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Cerebral vascular accident (CVA)	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Headache	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Psychiatric disorders
Mood alteration - Anxiety	0/4 (0%)		1/3 (33.3%)		1/3 (33.3%)		1/10 (10%)
Mood alteration - Depression	0/4 (0%)		1/3 (33.3%)		0/3 (0%)		2/10 (20%)
Reproductive system and breast disorders
Menstrual cramps	0/4 (0%)		1/3 (33.3%)		0/3 (0%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Hyperpigmentation	0/4 (0%)		0/3 (0%)		1/3 (33.3%)		0/10 (0%)
Rash/desquamation	0/4 (0%)		0/3 (0%)		0/3 (0%)		1/10 (10%)
Vascular disorders
Thrombosis	1/4 (25%)		0/3 (0%)		1/3 (33.3%)		1/10 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.