Ignite Creation Date:
2024-05-06 @ 1:10 AM
Last Modification Date:
2024-10-26 @ 10:59 AM
Study NCT ID:
NCT01740648
Status:
COMPLETED
Last Update Posted:
2023-09-18
First Post:
2012-11-30
Brief Title:
Trametinib Fluorouracil and Radiation Therapy Before Surgery in Treating Patients With Stage II-III Rectal Cancer
Sponsor:
Ohio State University Comprehensive Cancer Center
Organization:
Ohio State University Comprehensive Cancer Center
Study Overview
Official Title:
A Phase I Trial of MEK Inhibitor Trametinib in Combination With Neoadjuvant 5-Fluorouracil Chemoradiation in the Treatment of KRAS BRAF and NRAS-MUTANT Rectal Cancers
Status:
COMPLETED
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
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 trametinib when given together with fluorouracil and radiation therapy before surgery in treating patients with stage II-III rectal cancer Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Drugs used in chemotherapy such as fluorouracil work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Radiation therapy uses high-energy x-rays to kill tumor cells Giving trametinib together with fluorouracil and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed
Detailed Description:
PRIMARY OBJECTIVES
I To identify the maximally tolerated dose and recommended phase II dose of trametinib to be used in combination with 5FU fluorouracil and radiation in patients with rectal cancers
II To determine a recommended phase II dose of trametinib to be used with 5FU chemoradiation in patients with locally advanced rectal cancer
SECONDARY OBJECTIVES
I Evaluation of the tolerability and safety of the combination of trametinib and 5-FU chemoradiation in locally advanced rectal cancer
II Evaluation of post-therapy pathologic response
III Evaluation of the rate of local control disease-free survival and overall survival
IV Analysis of biomarkers - total mutations in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS v-raf murine sarcoma viral oncogene homolog B1BRAF and neuroblastoma RAS viral v-ras oncogene homolog NRAS as well as RASmitogen-activated protein kinase MAPK and phosphatidylinositol-45-bisphosphate 3-kinase PI3Kv-akt murine thymoma viral oncogene homolog 1 AKT pathway signaling pathways to potentially correlate with clinical benefit
OUTLINE This is a dose-escalation study of trametinib
Patients receive trametinib orally PO once daily QD on days -14 to -10 and 1-38 and fluorouracil intravenously IV continuously 5 days a week from days 1-38 Patients also undergo radiation therapy 5 days a week on days 1-33 Patients then undergo surgery 6-10 weeks later
Patients achieving negative surgical margins after complete resection of tumor receive postoperative chemotherapy comprising leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1 and 15 OR oxaliplatin IV over 2 hours leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1 and 15 Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up every 3 months for 2 years and then annually for 3 years
I To identify the maximally tolerated dose and recommended phase II dose of trametinib to be used in combination with 5FU fluorouracil and radiation in patients with rectal cancers
II To determine a recommended phase II dose of trametinib to be used with 5FU chemoradiation in patients with locally advanced rectal cancer
SECONDARY OBJECTIVES
I Evaluation of the tolerability and safety of the combination of trametinib and 5-FU chemoradiation in locally advanced rectal cancer
II Evaluation of post-therapy pathologic response
III Evaluation of the rate of local control disease-free survival and overall survival
IV Analysis of biomarkers - total mutations in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog KRAS v-raf murine sarcoma viral oncogene homolog B1BRAF and neuroblastoma RAS viral v-ras oncogene homolog NRAS as well as RASmitogen-activated protein kinase MAPK and phosphatidylinositol-45-bisphosphate 3-kinase PI3Kv-akt murine thymoma viral oncogene homolog 1 AKT pathway signaling pathways to potentially correlate with clinical benefit
OUTLINE This is a dose-escalation study of trametinib
Patients receive trametinib orally PO once daily QD on days -14 to -10 and 1-38 and fluorouracil intravenously IV continuously 5 days a week from days 1-38 Patients also undergo radiation therapy 5 days a week on days 1-33 Patients then undergo surgery 6-10 weeks later
Patients achieving negative surgical margins after complete resection of tumor receive postoperative chemotherapy comprising leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1 and 15 OR oxaliplatin IV over 2 hours leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1 and 15 Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up every 3 months for 2 years and then annually for 3 years
Study Oversight
Has Oversight DMC:
None
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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2012-02158 | REGISTRY | CTRP Clinical Trial Reporting Program | None |