Non Small Cell Lung CancerPhase 1/2NCT00794547
Phase I/II Calcitriol in Lung Cancer
A Phase 1/2 study testing Calcitriol in people with Non Small Cell Lung Cancer, run by University of Michigan Rogel Cancer Center at 4 sites in United States.
Trial summary
According to the Cancer Atlas, lung cancer remains the major cancer among the 10.9 million new cases of cancer diagnosed annually worldwide. The mortality from lung cancer is greater than the combined mortality for breast, colon and prostate cancer combined. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Calcitriol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 4 sitesUnited States
- Study dates
- Dec 2008to Aug 2013
- 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
- Proven histological or cytological diagnosis of stage IIIB (malignant pleural effusion) IV NSCLC.
- Age more than 18 years
- Performance status must be ECOG 0-1.
- No prior or concurrent malignancy, except non-melanoma skin cancer, or CIS of the cervix, unless documented disease-free for more than 2 years.
- No prior use of chemotherapy for stage IV NSCLC; Adjuvant therapy is permitted.
- Adequate bone marrow, hepatic, and renal function, as evidenced by the following: WBC 3.0 x 109/L, neutrophils 1.5 x 109 /L; platelet count 100 x 109/L; Hgb> 10 g/dL (may be transfused to 10g/dL); total bilirubin within the upper limit of the institutional normal range; (transaminases SGOT or SGPT) 1.5 times the upper limit of the institutional normal range. Creatinine within the upper limit of the institutional normal range; creatinine clearance >50 ml/min
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- Patients must have measurable or evaluable disease (not required for the phase I part of the study)
- Normal cardiac function with no history of uncontrolled heart disease
- Female patients must not be pregnant; they must be post-menopausal or practicing an accepted form of birth control. If pregnancy is a possibility, a pregnancy test will be required prior to initiation of therapy.
- Life expectancy of at least 12 weeks.
- Patient and investigator signed study-specific consent form, indicating the investigational nature of the study
- Patients must be accessible for treatment and follow-up.
- No chemotherapy or radiotherapy within 3 weeks of study entry defined here as day 1 of therapy with calcitriol plus chemotherapy (6 weeks for mitomycin C or a nitrosourea).
- No treatment with investigational drugs within 3 weeks of study entry.
- No other serious illness or medical condition including unstable cardiac disease requiring treatment, new onset crescendo or rest angina; history of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures; or active infection are permitted. No evidence of grade > 2 peripheral neuropathy. No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
- Palliative radiation is permitted (as long as marrow exposed not greater than 10%; please see Appendix IV for reference) At least 1 week since the last palliative XRT.
- Treated brain metastasis allowed with no waiting period following gamma knife and at least 2 weeks after whole brain XRT as long as neurologically stable.
Who cannot join
- Known hypersensitivity to Vitamin D, docetaxel, cisplatin
- Hypercalcemia (patients with serum albumin corrected calcium* > 10.7 mg/dL)
- History of renal/bladder stones over the past 10 years
- History of nephrectomy.
- Uncontrolled heart disease, unstable angina, heart failure, current digoxin therapy
- Thiazide, Digoxin or glucocorticoid therapy (except the pre-medication Dexamethasone used in the study as prescribed)
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- Unwillingness to stop calcium supplementation
- Concurrent use of Phenytoin, Barbiturates, Rifampin, Carbamazepine, Phenobarbital or St John's wort.
- Treatment with any investigational drug within 3 weeks before Day 1 of protocol
- Any unresolved toxicity (NCI CTCAE version 3.0,>2) (Please see appendix V for link)
- Pregnancy/Lactation
- Patients with IIIB NSCLC who are eligible for definitive chemoradiation.
- Ca corrected = Ca (measured) + (0.8 x (4 - albumin))
Trial locations and contacts
4 sites in 1 country.
United States4 sites
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, 48105
St. Joseph Mercy Hospital
Ann Arbor, Michigan, 48106
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
Official title: A Phase I/II Clinical Trial of Intravenous (IV) Calcitriol With Fixed Dose of Cisplatin and Docetaxel in Advanced Non-Small Cell Lung Cancer
According to the Cancer Atlas, lung cancer remains the major cancer among the 10.9 million new cases of cancer diagnosed annually worldwide. The mortality from lung cancer is greater than the combined mortality for breast, colon and prostate cancer combined. Most patients with metastatic non-small-cell lung cancer (NSCLC) are treated with platinum-based chemotherapy regimens. The drug combination of cisplatin and docetaxel is one of the commonly used regimens in metastatic NSCLC. Although both drugs are powerful disruptors of cell growth, positive therapeutic response rates to this therapy remain low for NSCLC patients, from 25% to 30%. While adding new biologics such as bevacizumab to the current treatment standard can improve treatment response, median survival for advanced NSCLC patients receiving this type of treatment remains low at under 12 months. Research studies have demonstrated that Vitamin D, and it's signaling pathways are important biological targets in cancer therapeutics. In vitro and in vivo calcitriol (1, 25 dihydroxycholecalciferol) is antiproliferative and potentiates the antitumor effects of cytotoxic agents (e.g. taxanes, platinum analogues). We have shown that administration of high doses of calcitriol and cisplatin is feasible and associated with complete tumor regressions in dogs with spontaneous cancers. Calcitriol has also shown to be synergistic with docetaxel both in preclinical as well as in a recent phase II clinical trial in prostate cancer. Based on these results and other supporting data from studies indicating that calcitriol functions as a potent and well tolerated anti-tumor agent when used in combination with drugs likes cisplatin and docetaxel, we hypothesize that introducing calcitriol into treatment regimes for NSCLC patients has the potential to demonstrably improve treatment response for these patients. The overall goals for conducting this phase I/II clinical study will be (1) to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of calcitriol in combination with cisplatin/docetaxel in patients with advanced NSCLC, (2) to assess the response rates of patients with advanced NSCLC to the combination of calcitriol with cisplatin/docetaxel, (3) to evaluate the pharmacokinetics (PK) of administering calcitriol intravenously at the MTD, and (4) to evaluate correlations between calcitriol PK and changes on specific coding regions of the gene associated with calcitriol breakdown.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Calcitriol
- Keywords
- lung cancer; nsclc
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CalcitriolDrug
Escalating dose of Calcitriol will be infused IV over 1 hour every 21 days.
CalcitriolDrug
In this portion of the study, all patients will get the same dose of calcitriol (determined from the Phase I study) along with the standard chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | In the Phase I part of the study, we will test the safety of calcitriol along with standard chemotherapy. In addition, the goal is to see what effects (good and bad) it has on you and your type of Non-Small Cell Lung Cancer. This study is ongoing. In this portion of the study, we are testing increasing doses of calcitriol in combination with standard chemotherapy. If 2/3 patients at any dose level experience side effects that are limiting, we will call the dose level below that dose the maximum tolerated dose. Receives: Drug: Calcitriol |
| 2 | Experimental | In the Phase II part of the study, we will find out the response of subjects' cancer has to the combination of a fixed dose of calcitriol (determined in the phase I study) with standard chemotherapy. Receives: Drug: Calcitriol |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of Intravenous Calcitriol When Administered Prior to Fixed Dose Cisplatin 75mg/m2 and Docetaxel 75 mg/m2, Every 3 Weeks in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
The primary objective was to determine the Maximum Tolerated Dose (MTD) of intravenous calcitriol when administered prior to fixed dose cisplatin 75mg/m2 and docetaxel 75 mg/m2, every 3 weeks in patients with advanced non-small cell lung cancer (NSCLC). Accrual duration for the study is 5 years.
Measured: 5 years
Number of Participants That Experience Grade 3 or Greater Neutropenia
The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. Toxicity was assessed, in part, by noting the number of participants that experience grade 3 or greater neutropenia in each phase of the trial. Toxicities were recorded using NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 and were followed for 30 days after the date of withdrawal from study drug.
Measured: 30 days after last dose
Median Time to Progression
The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, median time to progression was determined. Progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Measured: 5 years
Median Overall Survival
The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, overall survival was determined.
Measured: 5 years
Secondary outcomes (1)
Mean AUC 1,25-D3 Concentration at 12 and 24 Hours
The mean AUC (area under the curve) concentrations of 1,25-D3 from 0-12 hours and 0-24 hours will be calculated.
Measured: 12 and 24 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2008 (estimated)
- Study startDec 2008
- Primary completionOct 2011
- Study completionAug 2013
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nithya Ramnath, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00794547
- Sponsor's protocol ID
- UMCC 2008.042
- Other IDs
- HUM 21242
- Status last verified
- Nov 2017
- First submitted
- 19 Nov 2008
- Last updated
- 12 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ramnath N, Daignault-Newton S, Dy GK, Muindi JR, Adjei A, Elingrod VL, Kalemkerian GP, Cease KB, Stella PJ, Brenner DE, Troeschel S, Johnson CS, Trump DL. A phase I/II pharmacokinetic and pharmacogenomic study of calcitriol in combination with cisplatin and docetaxel in advanced non-small-cell lung cancer. Cancer Chemother Pharmacol. 2013 May;71(5):1173-82. doi: 10.1007/s00280-013-2109-x. Epub 2013 Feb 23.
PubMed 23435876
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Trial of Intravenous (IV) Calcitriol With Fixed Dose of Cisplatin and Docetaxel in Advanced Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00794547
- Acronym / sponsor ID
- UMCC 2008.042
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- lung cancer; nsclc
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Oct 2011 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 20 Nov 2008 (estimated)
- Results
- Posted 5 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
According to the Cancer Atlas, lung cancer remains the major cancer among the 10.9 million new cases of cancer diagnosed annually worldwide. The mortality from lung cancer is greater than the combined mortality for breast, colon and prostate cancer combined. Most patients with metastatic non-small-cell lung cancer (NSCLC) are treated with platinum-based chemotherapy regimens. The drug combination of cisplatin and docetaxel is one of the commonly used regimens in metastatic NSCLC. Although both drugs are powerful disruptors of cell growth, positive therapeutic response rates to this therapy remain low for NSCLC patients, from 25% to 30%. While adding new biologics such as bevacizumab to the current treatment standard can improve treatment response, median survival for advanced NSCLC patients receiving this type of treatment remains low at under 12 months. Research studies have demonstrated that Vitamin D, and it's signaling pathways are important biological targets in cancer therapeutics. In vitro and in vivo calcitriol (1, 25 dihydroxycholecalciferol) is antiproliferative and potentiates the antitumor effects of cytotoxic agents (e.g. taxanes, platinum analogues). We have shown that administration of high doses of calcitriol and cisplatin is feasible and associated with complete tumor regressions in dogs with spontaneous cancers. Calcitriol has also shown to be synergistic with docetaxel both in preclinical as well as in a recent phase II clinical trial in prostate cancer. Based on these results and other supporting data from studies indicating that calcitriol functions as a potent and well tolerated anti-tumor agent when used in combination with drugs likes cisplatin and docetaxel, we hypothesize that introducing calcitriol into treatment regimes for NSCLC patients has the potential to demonstrably improve treatment response for these patients. The overall goals for conducting this phase I/II clinical study will be (1) to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of calcitriol in combination with cisplatin/docetaxel in patients with advanced NSCLC, (2) to assess the response rates of patients with advanced NSCLC to the combination of calcitriol with cisplatin/docetaxel, (3) to evaluate the pharmacokinetics (PK) of administering calcitriol intravenously at the MTD, and (4) to evaluate correlations between calcitriol PK and changes on specific coding regions of the gene associated with calcitriol breakdown.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: CalcitriolIn the Phase I part of the study, we will test the safety of calcitriol along with standard chemotherapy. In addition, the goal is to see what effects (good and bad) it has on you and your type of Non-Small Cell Lung Cancer. This study is ongoing. In this portion of the study, we are testing increasing doses of calcitriol in combination with standard chemotherapy. If 2/3 patients at any dose level experience side effects that are limiting, we will call the dose level below that dose the maximum tolerated dose. |
| 2 | Experimental | Drug: CalcitriolIn the Phase II part of the study, we will find out the response of subjects' cancer has to the combination of a fixed dose of calcitriol (determined in the phase I study) with standard chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Proven histological or cytological diagnosis of stage IIIB (malignant pleural effusion) IV NSCLC.
- Age more than 18 years
- Performance status must be ECOG 0-1.
- No prior or concurrent malignancy, except non-melanoma skin cancer, or CIS of the cervix, unless documented disease-free for more than 2 years.
- No prior use of chemotherapy for stage IV NSCLC; Adjuvant therapy is permitted.
Key exclusion criteria (13 listed)
- Known hypersensitivity to Vitamin D, docetaxel, cisplatin
- Hypercalcemia (patients with serum albumin corrected calcium* > 10.7 mg/dL)
- History of renal/bladder stones over the past 10 years
- History of nephrectomy.
- Uncontrolled heart disease, unstable angina, heart failure, current digoxin therapy
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 |
|---|---|---|
| CalcitriolEscalating dose of Calcitriol will be infused IV over 1 hour every 21 days. | Drug | 1 |
| CalcitriolIn this portion of the study, all patients will get the same dose of calcitriol (determined from the Phase I study) along with the standard chemotherapy | Drug | 2 |
Primary outcome
MTD of Intravenous Calcitriol When Administered Prior to Fixed Dose Cisplatin 75mg/m2 and Docetaxel 75 mg/m2, Every 3 Weeks in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Time frame: 5 years
The primary objective was to determine the Maximum Tolerated Dose (MTD) of intravenous calcitriol when administered prior to fixed dose cisplatin 75mg/m2 and docetaxel 75 mg/m2, every 3 weeks in patients with advanced non-small cell lung cancer (NSCLC). Accrual duration for the study is 5 years.
Number of Participants That Experience Grade 3 or Greater Neutropenia
Time frame: 30 days after last dose
The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. Toxicity was assessed, in part, by noting the number of participants that experience grade 3 or greater neutropenia in each phase of the trial. Toxicities were recorded using NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 and were followed for 30 days after the date of withdrawal from study drug.
Median Time to Progression
Time frame: 5 years
The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, median time to progression was determined. Progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Median Overall Survival
Time frame: 5 years
The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, overall survival was determined.
1 secondary outcome
Mean AUC 1,25-D3 Concentration at 12 and 24 Hours
Time frame: 12 and 24 hours post dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23435876Ramnath N, Daignault-Newton S, Dy GK, Muindi JR, Adjei A, Elingrod VL, Kalemkerian GP, Cease KB, Stella PJ, Brenner DE, Troeschel S, Johnson CS, Trump DL. A phase I/II pharmacokinetic and pharmacogenomic study of calcitriol in combination with cisplatin and docetaxel in advanced non-small-cell lung cancer. Cancer Chemother Pharmacol. 2013 May;71(5):1173-82. doi: 10.1007/s00280-013-2109-x. Epub 2013 Feb 23.
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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.
Nithya Ramnath, MD principal investigator
University of Michigan Rogel Cancer Center
4 sites 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 in people with Non Small Cell Lung Cancer, run by University of Michigan Rogel Cancer Center at 4 sites 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 17 inclusion and 13 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: stopped early, as of the sponsor's last update on 12 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 5 May 2014). 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?
MTD of Intravenous Calcitriol When Administered Prior to Fixed Dose Cisplatin 75mg/m2 and Docetaxel 75 mg/m2, Every 3 Weeks in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) (time frame: 5 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00794547, which also lists 1 linked publication.
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 12 Dec 2017.