Metastatic MelanomaPhase 1/2NCT00301067
Phase I/II Study of High-Dose Calcitriol Plus Temodar for Patients With Metastatic Melanoma
A Phase 1/2 study testing Calcitriol and Temozolomide in people with Metastatic Melanoma, run by Northwestern University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- Calcitriol and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jan 2005to 9 Jul 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611-3013
About this study
Official title: A Phase I/II Study of High-Dose Calcitriol in Combination With Temozolomide for Patients With Metastatic Melanoma
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.
Read the 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.
- Conditions
- Metastatic Melanoma
- Being tested
- Calcitriol, Temozolomide
- Keywords
- stage IV melanoma, recurrent melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CalcitriolDietary supplement
The patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle
TemozolomideDrug
The patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - Temozolomide and Calcitriol | Experimental | 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. Receives: Dietary Supplement: Calcitriol; Drug: Temozolomide |
| Cohort 2 - Temozolomide and Calcitriol | Experimental | 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. Receives: Dietary Supplement: Calcitriol; Drug: Temozolomide |
| Cohort 3 - Temozolomide and Calcitriol | Experimental | 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. Receives: Dietary Supplement: Calcitriol; Drug: Temozolomide |
| Expansion - Temozolomide and Calcitriol | Experimental | 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. Receives: Dietary Supplement: Calcitriol; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and Frequency of Dose Limiting Toxicities (DLTs) With High-dose Calcitriol in Combination With Temozolomide
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.
Measured: From start of treatment, up to 12 cycles where 1 cycle equals 28 days
Number of Patients With Toxicity
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.
Measured: 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
Secondary outcomes (2)
Tumor Response
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.
Measured: At baseline and every 8 weeks during treatment for a maximum of 12 cycles where one cycle equals 28 days.
The Relationship Between Vitamin D-receptor Gene Polymorphisms and Tumor Response
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.
Measured: Baseline and at disease progression or when patient goes off study up to a maximum of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2006 (estimated)
- Study start30 Jan 2005
- Primary completion5 Apr 2012
- Study completion9 Jul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Timothy M. Kuzel, MD, Study chair, Robert H. Lurie Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00301067
- Sponsor's protocol ID
- NU 05M1
- Other IDs
- P30CA060553, NU-05M1, NU-0310-093, SPRI-NU-05M1
- Status last verified
- May 2019
- First submitted
- 8 Mar 2006
- Last updated
- 4 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of High-Dose Calcitriol in Combination With Temozolomide for Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00301067
- Acronym / sponsor ID
- NU 05M1
- Conditions
- Metastatic Melanoma
- Keywords
- stage IV melanoma, recurrent melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 30 Jan 2005 (actual)
- Primary completion
- 5 Apr 2012 (actual)
- Study completion
- 9 Jul 2012 (actual)
- First posted
- 10 Mar 2006 (estimated)
- Results
- Posted 28 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - Temozolomide and Calcitriol | Experimental | Dietary Supplement: Calcitriol, Drug: TemozolomideTemozolomide 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. |
| Cohort 2 - Temozolomide and Calcitriol | Experimental | Dietary Supplement: Calcitriol, Drug: TemozolomideTemozolomide 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. |
| Cohort 3 - Temozolomide and Calcitriol | Experimental | Dietary Supplement: Calcitriol, Drug: TemozolomideTemozolomide 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. |
| Expansion - Temozolomide and Calcitriol | Experimental | Dietary Supplement: Calcitriol, Drug: TemozolomideTemozolomide 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed malignant melanoma
- Stage IV disease
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CalcitriolThe patient will receive calcitriol in capsule form by mouth on Days 1 and 15 of every cycle | Dietary supplement | Cohort 1 - Temozolomide and Calcitriol, Cohort 2 - Temozolomide and Calcitriol, Cohort 3 - Temozolomide and Calcitriol, Expansion - Temozolomide and Calcitriol |
| TemozolomideThe patient will receive temozolomide in capsule form by mouth on Days 2-8 and 16-22 of each 28 study treatment cycle | Drug | Cohort 1 - Temozolomide and Calcitriol, Cohort 2 - Temozolomide and Calcitriol, Cohort 3 - Temozolomide and Calcitriol, Expansion - Temozolomide and Calcitriol |
Primary outcome
Number and Frequency of Dose Limiting Toxicities (DLTs) With High-dose Calcitriol in Combination With Temozolomide
Time frame: 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.
Number of Patients With Toxicity
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
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.
2 secondary outcomes
Tumor Response
Time frame: At baseline and every 8 weeks during treatment for a maximum of 12 cycles where one cycle equals 28 days.
The Relationship Between Vitamin D-receptor Gene Polymorphisms and Tumor Response
Time frame: Baseline and at disease progression or when patient goes off study up to a maximum of 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy M. Kuzel, MD study chair
Robert H. Lurie Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Calcitriol and Temozolomide in people with Metastatic Melanoma, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and Frequency of Dose Limiting Toxicities (DLTs) With High-dose Calcitriol in Combination With Temozolomide (time frame: From start of treatment, up to 12 cycles where 1 cycle equals 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2019.