Ignite Creation Date:
2025-12-24 @ 6:59 PM
Ignite Modification Date:
2025-12-24 @ 6:59 PM
Study NCT ID:
NCT04406857
Status:
TERMINATED
Last Update Posted:
2025-02-26
First Post:
2020-05-28
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Testing the Addition of a Radiation Sensitizing Drug, IPdR, to the Usual Chemotherapy Treatment (Capecitabine) During Radiation Therapy for Rectal Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase 1 Study of IPdR in Combination With Capecitabine and Radiotherapy in Rectal Cancer
Status:
TERMINATED
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Inadequate accrual rate
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the side effects and best dose of ropidoxuridine and how well it works when added to the usual chemotherapy treatment (capecitabine) during radiation therapy for the treatment of patients with stage II-III rectal cancer. Ropidoxuridine may help radiation therapy work better by making cancer cells more sensitive to the radiation therapy. Chemotherapy drugs, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. This study is being done to find out whether ropidoxuridine in addition to capecitabine and radiation therapy works better in treating patients with rectal cancer.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of oral (PO) ropidoxuridine (IPdR) when administered with capecitabine (825 mg/m\^2 twice daily \[BID\]) and radiation therapy (RT) (50.4 Gy in 28 fractions).
II. To determine the toxicities Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 of the combined modality therapy, IPdR + capecitabine + RT.
SECONDARY OBJECTIVES:
I. To establish the pharmacokinetics (PK) of once daily (QD) IPdR when combined with capecitabine.
II. To evaluate iododeoxyuridine (IUdR) incorporation in circulating granulocytes and correlate these levels with IPdR plasma PK and clinical/laboratory toxicities.
III. To assess IUdR incorporation in tumor cells obtained from the surgical resection specimen and correlate IUdR incorporation in tumor cells with IPdR PK.
IV. To assess IUdR incorporation in tumor cells obtained from the surgical resection specimen and correlate IUdR incorporation in tumor cells with tumor response as measured by pathological complete response (pCR) rate and neoadjuvant rectal (NAR) score.
V. To determine the pCR rate of IPdR + capecitabine + RT at the IPdR MTD as a measure of anti-tumor activity.
VI. To determine the NAR score of IPdR + capecitabine + RT at the IPdR MTD.
EXPLORATORY OBJECTIVES:
I. To explore the relationship between extent of exposure to RT and the development and severity of adverse events.
II. To explore the drug/drug/metabolite interactions between capecitabine, IPdR, and their metabolites.
OUTLINE: This is a phase IA, dose-escalation study of ropidoxuridine followed by a phase IB study.
Patients receive ropidoxuridine PO QD over 7 days per week and capecitabine PO BID over 6 days per week for 6 weeks. Patients also undergo radiation therapy over 1 fraction per day for 5 days per week (Monday-Friday) during weeks 1-5 and for 3 days during week 6 in the absence of disease progression or unacceptable toxicity. Approximately 8-12 weeks after completion of treatment with ropidoxuridine, capecitabine, and radiation therapy, patients undergo standard of care surgery.
After completion of study treatment, patients are followed up at 4 and 8-12 weeks following chemoradiation therapy.
I. To determine the maximum tolerated dose (MTD) of oral (PO) ropidoxuridine (IPdR) when administered with capecitabine (825 mg/m\^2 twice daily \[BID\]) and radiation therapy (RT) (50.4 Gy in 28 fractions).
II. To determine the toxicities Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 of the combined modality therapy, IPdR + capecitabine + RT.
SECONDARY OBJECTIVES:
I. To establish the pharmacokinetics (PK) of once daily (QD) IPdR when combined with capecitabine.
II. To evaluate iododeoxyuridine (IUdR) incorporation in circulating granulocytes and correlate these levels with IPdR plasma PK and clinical/laboratory toxicities.
III. To assess IUdR incorporation in tumor cells obtained from the surgical resection specimen and correlate IUdR incorporation in tumor cells with IPdR PK.
IV. To assess IUdR incorporation in tumor cells obtained from the surgical resection specimen and correlate IUdR incorporation in tumor cells with tumor response as measured by pathological complete response (pCR) rate and neoadjuvant rectal (NAR) score.
V. To determine the pCR rate of IPdR + capecitabine + RT at the IPdR MTD as a measure of anti-tumor activity.
VI. To determine the NAR score of IPdR + capecitabine + RT at the IPdR MTD.
EXPLORATORY OBJECTIVES:
I. To explore the relationship between extent of exposure to RT and the development and severity of adverse events.
II. To explore the drug/drug/metabolite interactions between capecitabine, IPdR, and their metabolites.
OUTLINE: This is a phase IA, dose-escalation study of ropidoxuridine followed by a phase IB study.
Patients receive ropidoxuridine PO QD over 7 days per week and capecitabine PO BID over 6 days per week for 6 weeks. Patients also undergo radiation therapy over 1 fraction per day for 5 days per week (Monday-Friday) during weeks 1-5 and for 3 days during week 6 in the absence of disease progression or unacceptable toxicity. Approximately 8-12 weeks after completion of treatment with ropidoxuridine, capecitabine, and radiation therapy, patients undergo standard of care surgery.
After completion of study treatment, patients are followed up at 4 and 8-12 weeks following chemoradiation therapy.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2020-03610 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 10410 | OTHER | Ohio State University Comprehensive Cancer Center LAO | View | |
| 10410 | OTHER | CTEP | View | |
| UM1CA186644 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186712 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186716 | NIH | None | https://reporter.nih.gov/quic… | View |