Protocol Summary

Protocol No.: OCR15492

Sponsor Protocol No.: NRG-GI002

Study Title
A Phase II Clinical Trial Platform of Sensitization Utilizing Total Neoadjuvant Therapy (TNT) in Rectal Cancer

Principal Investigator(s)
George, Thomas

Objective
This randomized phase II trial studies how well veliparib works with combination chemotherapy and radiation therapy in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as modified (m)FOLFOX6 regimen, 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. Giving veliparib with combination chemotherapy and radiation therapy may kill more tumor cells and giving it before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Description
ARM I: Patients receive mFOLFOX6 regimen consisting of oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo radiation therapy and receive capecitabine orally (PO) twice daily (BID) Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive mFOLFOX6 regimen consisting of oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. 3-4 weeks after last does of mFOLFOX6 patient undergo radiation therapy and receive capecitabine PO BID and veliparib PO BID Monday-Friday for 5 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 6 months for up to 3 years.

Phase: Phase II (Cancer Control)

Age Group: Adult

Scope: National

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 18 years old and older
2. The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
4. Diagnosis of adenocarcinoma of the rectum with the major portion of the tumor intact; Note: prior to randomization, the investigator must specify and document the following:
- Distance of the lowest tumor margin from the anal verge; and
- Intent for sphincter sparing surgical resection or not according to the primary surgeon
5. The tumor must be clinically determined to be locally advanced stage II or stage III rectal cancer, defined as meeting any ONE of the following criteria:
- Distal location: cT3-4 = - Bulky: any cT4 with the majority of the untreated tumor - High risk for metastatic disease with 4 or more regional lymph nodes (cN2)
- Not a candidate for sphincter-sparing surgical resection prior to neoadjuvant therapy (as planned by the primary surgeon)
Note: clinical stage of the primary tumor and nodes may be determined locally by endoscopic ultrasound or abdominal/pelvic MRI (MRI is preferred); CT scan with IV contrast is acceptable provided there is evidence of T4 and/or N2 disease; clinical nodal or "cN" status for eligibility includes the total number of nodes (N2 = 4 or more) in the mesorectal and superior rectal stations measuring >= 1.0 cm in any axis on cross sectional or endoscopic imaging
6. At least two (2) untreated core biopsy specimens from the untreated tumor (formalin-fixed, paraffin-embedded [FFPE]) must have been collected previously and be available for submission per protocol requirements
7. Patients must have the ability to swallow and retain oral medication
8. Absolute neutrophil count (ANC) must be >= 1200/mm^3
9. Platelet count must be >= 100,000/mm^3
10. Hemoglobin must be >= 10 g/dL
11. Total bilirubin must be = ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin
12. Alkaline phosphatase must be =13. Aspartate aminotransferase (AST) must be = Note: if alanine aminotransferase (ALT) is performed instead of AST (per institution's standard practice), the ALT value must be == ULN but =14. Serum creatinine = 60 mL/min
15. Serum potassium, magnesium, and calcium levels within 28 days before randomization must be within normal limits (WNL) for the lab
International normalized ratio of prothrombin time (INR) and prothrombin time (PT) within 28 days before randomization must be WNL for the lab; patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history

** Contact the study team for complete eligibility details

Applicable Disease Sites
Gastrointestinal Cancer

Participating Institutions
UF Gainesville : Elena Nelson

Contact
Elena Nelson
Phone: +1 352-265-0680 ext. 50144

Email: eab1109@ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02921256