Trametinib, Fluorouracil, and Radiation Therapy Before Surgery in Treating Patients With Stage II-III Rectal Cancer

Conditions

• Recurrent Rectal Cancer
• Stage IIA Rectal Cancer
• Stage IIB Rectal Cancer
• Stage IIC Rectal Cancer
• Stage IIIA Rectal Cancer
• Stage IIIB Rectal Cancer
• Stage IIIC Rectal Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• trametinib — DRUG
  Trametinib will be given for 5-day lead-in period by mouth daily Monday-Friday starting at day -14 through -10 and concurrently for the duration of radiation therapy (approximately days 1-38).The dose of Trametinib will be escalated: 0.5 mg, 1.0 mg, 2mg. If the 2 mg dose level causes DLT (dose-limiting toxicity)in 2 out of 6 patients and the 1mg dose level was acceptable, then a 1.5 mg dose cohort will be used.
• fluorouracil — DRUG
  Will be administered as a continuous infusion over 120 hours at a dose of 225 mg/m2/day on Monday to Friday of every week starting day 1-38.
• radiation therapy — RADIATION
  Radiation therapy will be delivered to the pelvis during (approximately) days 1-33 (five days a week, Mondays through Fridays for 25 fractions) using a 3-field or 4-field 3-D conformal plan to the primary tumor, surrounding soft tissues, and at risk lymph node stations (peri-rectal, presacral, internal iliac, with or without external iliac) to a total dose of 45 Gy in 1.8 Gy daily fractions. A boost radiation field will be delivered during (approximately) days 36-38. The boost will encompass the primary rectal tumor and involved lymph nodes with a 2-2.5 cm margin, which should include the presacral space. The boost dose will be 5.4 Gy in 1.8 Gy fractions for a total dose of 50.4 Gy.

Study Details

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

Key Dates

Start date

Nov 26, 2012

Status verified

Sep 2023

Primary completion

Sep 29, 2021

Completion

Sep 29, 2021

Study Design

Enrollment

19 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Treatment (trametinib, fluorouracil, radiation, surgery)
  Patients receive trametinib PO (by mouth) QD (daily) on days -14 through -10 and 1-38 and fluorouracil 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.

Primary Outcome Measure

Identify the maximally tolerated dose of Trametinib to be used in combination with 5FU and radiation in patients with rectal cancers. [ Time Frame: up to 9 weeks ]

Locations (4)

Find similar trials in St Louis, MO