Trial Outcomes & Findings for Phase I/II Study of High-Dose Calcitriol Plus Temodar for Patients With Metastatic Melanoma (NCT NCT00301067)

Last Updated: 2019-06-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

20 participants

Primary outcome timeframe

From start of treatment, up to 12 cycles where 1 cycle equals 28 days

Results posted on

2019-06-04

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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. 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	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. 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	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. 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	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. 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
Completed DLT Period/1st Cycle STARTED	4	3	3	10
Completed DLT Period/1st Cycle COMPLETED	3	3	3	9
Completed DLT Period/1st Cycle NOT COMPLETED	1	0	0	1
Reached 1st Response/2 Cycles STARTED	3	3	3	9
Reached 1st Response/2 Cycles COMPLETED	1	2	2	7
Reached 1st Response/2 Cycles NOT COMPLETED	2	1	1	2
Completed 4 Cycles of Treatment STARTED	1	2	2	7
Completed 4 Cycles of Treatment COMPLETED	0	1	0	2
Completed 4 Cycles of Treatment NOT COMPLETED	1	1	2	5
Completed 12 Cycles of Treatment STARTED	0	1	0	2
Completed 12 Cycles of Treatment COMPLETED	0	0	0	0
Completed 12 Cycles of Treatment NOT COMPLETED	0	1	0	2
Follow up Until Death STARTED	4	3	3	3
Follow up Until Death COMPLETED	3	3	3	2
Follow up Until Death NOT COMPLETED	1	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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. 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	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. 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	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. 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	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. 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
Completed DLT Period/1st Cycle Progressive Disease	1	0	0	1
Reached 1st Response/2 Cycles Progressive Disease	2	1	1	2
Completed 4 Cycles of Treatment Progressive disease	1	1	2	5
Completed 12 Cycles of Treatment Progressive Disease	0	1	0	1
Completed 12 Cycles of Treatment Adverse Event	0	0	0	1
Follow up Until Death Alive at last data cut point	1	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Temozolomide and Calcitriol (Cohort 1-3+Expansion) n=20 Participants 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
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=93 Participants
Age, Categorical >=65 years	9 Participants n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	15 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	20 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	20 Participants n=93 Participants

PRIMARY outcome

Timeframe: From start of treatment, up to 12 cycles where 1 cycle equals 28 days

Population: 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.

Outcome measures

Outcome measures
Measure	Cohort 1 - Temozolomide and Calcitriol n=3 Participants 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	Cohort 2 - Temozolomide and Calcitriol n=3 Participants 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	Cohort 3 - Temozolomide and Calcitriol n=3 Participants 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	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. 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
Number and Frequency of Dose Limiting Toxicities (DLTs) With High-dose Calcitriol in Combination With Temozolomide	0 DLT	0 DLT	0 DLT	—

PRIMARY outcome

Timeframe: 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

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

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.

Outcome measures

Outcome measures
Measure	Cohort 1 - Temozolomide and Calcitriol n=4 Participants 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	Cohort 2 - Temozolomide and Calcitriol n=3 Participants 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	Cohort 3 - Temozolomide and Calcitriol n=3 Participants 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	Expansion - Temozolomide and Calcitriol n=9 Participants 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
Number of Patients With Toxicity Fatigue	0 participants	0 participants	0 participants	1 participants
Number of Patients With Toxicity Thrombocytopenia	1 participants	0 participants	0 participants	1 participants
Number of Patients With Toxicity Vascular	1 participants	0 participants	0 participants	1 participants
Number of Patients With Toxicity Nausea	0 participants	0 participants	1 participants	0 participants
Number of Patients With Toxicity Vomiting	0 participants	0 participants	1 participants	0 participants
Number of Patients With Toxicity Leukopenia	0 participants	0 participants	1 participants	1 participants
Number of Patients With Toxicity Anemia	0 participants	0 participants	0 participants	2 participants
Number of Patients With Toxicity Lymphopenia	0 participants	0 participants	0 participants	2 participants
Number of Patients With Toxicity Hemorrhage	0 participants	0 participants	0 participants	1 participants
Number of Patients With Toxicity Rash	0 participants	0 participants	0 participants	1 participants
Number of Patients With Toxicity Anorexia	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: At baseline and every 8 weeks during treatment for a maximum of 12 cycles where one cycle equals 28 days.

Population: 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)

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.

Outcome measures

Outcome measures
Measure	Cohort 1 - Temozolomide and Calcitriol n=20 Participants 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	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. 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	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. 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	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. 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
Tumor Response Complete Response	0 Participants	—	—	—
Tumor Response Partial Response	2 Participants	—	—	—
Tumor Response Progressive Disease	17 Participants	—	—	—
Tumor Response Stable Disease	1 Participants	—	—	—

SECONDARY outcome

Timeframe: Baseline and at disease progression or when patient goes off study up to a maximum of 12 months

Population: 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.

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.

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: From the start of treatment, every 2 cycles where 1 cycle equals 28 days, for a maximum of 12 cycles

Population: 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)

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.

Outcome measures

Outcome measures
Measure	Cohort 1 - Temozolomide and Calcitriol n=20 Participants 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	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. 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	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. 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	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. 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 Response Rate	2 Participants	—	—	—

POST_HOC outcome

Timeframe: From the start of treatment, until progressive disease, up to 12 months

Population: 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)

Time to progression (TTP) is measured from the start of treatment until the time of first documentation of disease progression.

Outcome measures

Outcome measures
Measure	Cohort 1 - Temozolomide and Calcitriol n=20 Participants 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	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. 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	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. 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	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. 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
Time to Progression	1.81 Months Interval 1.15 to 1.99	—	—	—

POST_HOC outcome

Timeframe: From the first day of treatment until death from any cause, up to a maximum of 6 and half years

Population: 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)

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.

Outcome measures

Outcome measures
Measure	Cohort 1 - Temozolomide and Calcitriol n=20 Participants 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	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. 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	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. 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	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. 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 Survival	5.5 Months Interval 2.7 to 12.3	—	—	—

POST_HOC outcome

Timeframe: at baseline and until death from any cause up to 6 and half years

Population: 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)

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.

Outcome measures

Outcome measures
Measure	Cohort 1 - Temozolomide and Calcitriol n=17 Participants 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	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. 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	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. 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	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. 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 Survival (OS) Stratified by Vitamin D-Receptor (VDR) Gene Polymorphisms VDR genotype (tt+/-ff)	3.8 Months Interval 2.0 to 5.7	—	—	—
Overall Survival (OS) Stratified by Vitamin D-Receptor (VDR) Gene Polymorphisms non tt+/-ff VDR genotype	7.4 Months Interval 3.0 to 12.3	—	—	—

Adverse Events

Cohort 1 - Temozolomide and Calcitriol

Serious events: 2 serious events

Other events: 4 other events

Deaths: 3 deaths

Cohort 2 - Temozolomide and Calcitriol

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

Cohort 3 - Temozolomide and Calcitriol

Serious events: 2 serious events

Other events: 3 other events

Deaths: 3 deaths

Expansion - Temozolomide and Calcitriol

Serious events: 4 serious events

Other events: 10 other events

Deaths: 9 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 - Temozolomide and Calcitriol n=4 participants at risk 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	Cohort 2 - Temozolomide and Calcitriol n=3 participants at risk 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	Cohort 3 - Temozolomide and Calcitriol n=3 participants at risk 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	Expansion - Temozolomide and Calcitriol n=10 participants at risk 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
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/4 • 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.	0.00% 0/3 • 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.	0.00% 0/3 • 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.	10.0% 1/10 • Number of events 1 • 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.
Gastrointestinal disorders Nausea and vomiting	0.00% 0/4 • 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.	0.00% 0/3 • 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.	33.3% 1/3 • Number of events 1 • 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.	0.00% 0/10 • 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.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/4 • 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.	0.00% 0/3 • 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.	0.00% 0/3 • 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.	10.0% 1/10 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rapidly declining performance status	0.00% 0/4 • 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.	33.3% 1/3 • Number of events 1 • 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.	0.00% 0/3 • 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.	0.00% 0/10 • 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.
Nervous system disorders Confusion	25.0% 1/4 • Number of events 1 • 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.	0.00% 0/3 • 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.	0.00% 0/3 • 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.	0.00% 0/10 • 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.
Nervous system disorders Slurred speech and drooling	0.00% 0/4 • 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.	0.00% 0/3 • 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.	0.00% 0/3 • 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.	10.0% 1/10 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Pneumonia	25.0% 1/4 • Number of events 1 • 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.	0.00% 0/3 • 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.	0.00% 0/3 • 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.	0.00% 0/10 • 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolus	0.00% 0/4 • 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.	0.00% 0/3 • 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.	0.00% 0/3 • 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.	10.0% 1/10 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders Rash	0.00% 0/4 • 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.	0.00% 0/3 • 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.	0.00% 0/3 • 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.	10.0% 1/10 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death related to disease	0.00% 0/4 • 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.	0.00% 0/3 • 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.	33.3% 1/3 • Number of events 1 • 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.	0.00% 0/10 • 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.

Other adverse events

Additional Information

Clinical Trials Office

Northwestern University

Phone: 312-695-1301

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place