Background:
Most patients who have surgery for cancer that has metastasized (spread) to the lungs later get more metastases that cannot be treated with surgery or chemotherapy. The drug resistance may be due to DNA changes in cancer cells that activate some genes and turn others off. Researchers want to test a combination of drugs for people with metasteses. Decitabine (DAC) may reverse the DNA changes. Tetrahydrouridine (THU) makes DAC last longer. Celecoxib may slow the progression of cancer.
Objectives:
To determine a safe dose of DAC and THU by mouth. To see if DAC-THU with or without celecoxib reactivates genes in lung metastases.
Eligibility:
Adults 18 years and older, with cancer in both lungs that can be treated with surgery.
Design:
Participants will be screened with:
Blood, lung, and heart tests
Scans
Tests for viruses
Pregnancy test
Participants will have blood and stool tests.
They will have surgery to remove metasteses in 1 lung.
About 3 weeks later, they will have lung scans. If the disease is not back, participants will get DAC and THU with or without celecoxib, by mouth for 6 weeks.
Participants will have more scans. If the disease is not worse, they will continue the study drugs for 4 more weeks.
Participants will have more scans and heart and lung tests. They will have surgery to remove metasteses from the other lung.
Participants will have weekly blood and urine tests, plus several blood draws the first 2 days of taking the drugs.
Participants will have exams and blood tests before each surgery.
Participants will have follow-up visits 1 and 3 months after the second surgery.
Condition or disease | Intervention/treatment | Phase |
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Neoplasm Metastasis Sarcoma Neoplasms, Germ Cell and Embryonal Melanoma | Drug: decitabine (DAC) Drug: Tetrahydrouridine (THU) Drug: Celecoxib | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 0 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase I Evaluation of Adjuvant Oral Decitabine and Tetrahydrouridine With or Without Celecoxib in Patients Undergoing Pulmonary Metastasectomy |
Study Start Date : | July 7, 2016 |
Actual Primary Completion Date : | April 26, 2017 |
Actual Study Completion Date : | April 26, 2017 |
Arm | Intervention/treatment |
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Experimental: Dose escalation cohort
dose escalation cohort
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Drug: decitabine (DAC)
Administered IV at increasing frequency or dose from 3-5 times per week for 8-12 weeks
Drug: Tetrahydrouridine (THU) Administered IV at increasing frequency or dose from 3-5 times per week for 8-12 weeks
|
Experimental: Expansion cohort
expansion cohort at MTD
|
Drug: decitabine (DAC)
Administered IV at increasing frequency or dose from 3-5 times per week for 8-12 weeks
Drug: Tetrahydrouridine (THU) Administered IV at increasing frequency or dose from 3-5 times per week for 8-12 weeks
|
Active Comparator: expansion cohort with celecoxib
expansion cohort at MTD with celecoxib
|
Drug: decitabine (DAC)
Administered IV at increasing frequency or dose from 3-5 times per week for 8-12 weeks
Drug: Tetrahydrouridine (THU) Administered IV at increasing frequency or dose from 3-5 times per week for 8-12 weeks
Drug: Celecoxib 400 mg orally twice a day every day for while on DAC-THU therapy
|
Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:
EXCLUSION CRITERIA:
Principal Investigator: | David S Schrump, M.D. | National Cancer Institute (NCI) |
Tracking Information | ||||
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First Submitted Date ICMJE | July 19, 2016 | |||
First Posted Date ICMJE | July 21, 2016 | |||
Last Update Posted Date | July 5, 2018 | |||
Study Start Date ICMJE | July 7, 2016 | |||
Actual Primary Completion Date | April 26, 2017 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE | Not Provided | |||
Original Secondary Outcome Measures ICMJE | Not Provided | |||
Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Adjuvant Oral Decitabine and Tetrahydrouridine With or Without Celecoxib in People Undergoing Pulmonary Metastasectomy | |||
Official Title ICMJE | Phase I Evaluation of Adjuvant Oral Decitabine and Tetrahydrouridine With or Without Celecoxib in Patients Undergoing Pulmonary Metastasectomy | |||
Brief Summary |
Background: Most patients who have surgery for cancer that has metastasized (spread) to the lungs later get more metastases that cannot be treated with surgery or chemotherapy. The drug resistance may be due to DNA changes in cancer cells that activate some genes and turn others off. Researchers want to test a combination of drugs for people with metasteses. Decitabine (DAC) may reverse the DNA changes. Tetrahydrouridine (THU) makes DAC last longer. Celecoxib may slow the progression of cancer. Objectives: To determine a safe dose of DAC and THU by mouth. To see if DAC-THU with or without celecoxib reactivates genes in lung metastases. Eligibility: Adults 18 years and older, with cancer in both lungs that can be treated with surgery. Design: Participants will be screened with: Blood, lung, and heart tests Scans Tests for viruses Pregnancy test Participants will have blood and stool tests. They will have surgery to remove metasteses in 1 lung. About 3 weeks later, they will have lung scans. If the disease is not back, participants will get DAC and THU with or without celecoxib, by mouth for 6 weeks. Participants will have more scans. If the disease is not worse, they will continue the study drugs for 4 more weeks. Participants will have more scans and heart and lung tests. They will have surgery to remove metasteses from the other lung. Participants will have weekly blood and urine tests, plus several blood draws the first 2 days of taking the drugs. Participants will have exams and blood tests before each surgery. Participants will have follow-up visits 1 and 3 months after the second surgery. |
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Detailed Description |
Background:
Objectives: -To determine the pharmacokinetics, toxicities and maximum tolerated dose of oral DAC and THU with or without celecoxib in patients undergoing resection of pulmonary metastases Eligibility:
Design:
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 1 | |||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Withdrawn | |||
Actual Enrollment ICMJE |
0 | |||
Original Estimated Enrollment ICMJE |
46 | |||
Actual Study Completion Date ICMJE | April 26, 2017 | |||
Actual Primary Completion Date | April 26, 2017 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE |
EXCLUSION CRITERIA:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 99 Years (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Not Provided | |||
Removed Location Countries | United States | |||
Administrative Information | ||||
NCT Number ICMJE | NCT02839694 | |||
Other Study ID Numbers ICMJE | 160146 16-C-0146 |
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Has Data Monitoring Committee | Not Provided | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Responsible Party | National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) | |||
Study Sponsor ICMJE | National Cancer Institute (NCI) | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | National Institutes of Health Clinical Center (CC) | |||
Verification Date | April 26, 2017 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |