A Phase II Clinical Trial for Rectal Cancer

July 16, 2019

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

  • Clinical Trial Information

    Trial Contact: De Leon, Ma Theresa; Jarquin-Castillo, Katherine

    Trial Phone: 321.841.8284 ; 321.841.1077

  • IRB No: NRG-GI002

    Protocol Abbrev: NRG-GI002

    Principal Investigator: Omar R. Kayaleh, MD

    Phase: Drug: Phase II

    Age Group: Adult

    Treatment: Capecitabine, Fluorouracil, Radiation: Intensity-Modulated Radiation Therapy, Leucovorin Calcium, Oxaliplatin, Veliparib

    Therapies Involved: Oncology: Neo-adjuvant

    ClinicalTrials.gov ID: NCT02921256

  • 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.

  • Key Eligibility

    1. •  The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines

    2. •  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

    3. •  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

    4. •  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 =< 5 cm from the anal verge, any N (as defined by measurement on magnetic resonance imaging [MRI], transrectal ultrasound [ERUS]/pelvic computed tomography [CT] (with IV contrast) scan or palpable on digital rectal examination [DRE])
    ◦Bulky: any cT4 with the majority of the untreated tumor < 12 cm from the anal verge or below the peritoneal reflection as determined by the treating surgeon, or evidence that the tumor is adjacent to (defined as within 3 mm of) the mesorectal fascia on MRI or ERUS/pelvic CT (with IV contrast) scan
    ◦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

    5. •  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

    6. •  Patients must have the ability to swallow and retain oral medication

    7. •  Absolute neutrophil count (ANC) must be >= 1200/mm^3
    •  Platelet count must be >= 100,000/mm^3
    •  Hemoglobin must be >= 10 g/dL
    •  Total bilirubin must be =< ULN (upper limit of normal) for the lab unless the patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin
    •  Alkaline phosphatase must be =< 3 x ULN for the lab
    •  Serum creatinine =< ULN for the lab and measured or calculated creatinine clearance > 60 mL/min
    •  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

    •  Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease must:
    ◦Have a cluster of differentiation (CD)4 count >= 200 cells/uL within 30 days before beginning study therapy
    ◦Be off all antiretroviral therapy (prophylaxis/treatment) more than 60 days before beginning study therapy, and
    ◦Have no evidence of opportunistic infections

    •  Pregnancy test done within 14 days before randomization must be negative (for women of childbearing potential only); pregnancy testing should be performed according to institutional standards