Chemotherapy, Radiation Therapy, and Midostaurin in Treating Patients with Locally Advanced Rectal Cancer

Inclusion Criteria

• Participants must have histologically or cytologically confirmed adenocarcinoma of the rectum
• Patients must have T3/4 or N+ disease by magnetic resonance imaging (MRI) or endoscopic ultrasound
• No evidence of metastases based on radiological imaging (computed tomography [CT], MRI or positron emission tomography [PET]/CT including chest abdomen and pelvis)
• Life expectancy of greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin (Hgb) >= 8 g/dl
• Total bilirubin (T. Bili) =< 1.5 X upper limit of normal (ULN)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 1.5 X ULN
• Creatinine (Creat) =< 1.5 X ULN
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months of midostaurin medication; highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment * Male sterilization (at least 6 months prior to screening); for female subjects on the study the vasectomized male partner should be the sole partner for that subject * Combination of any two of the following (a+b or a+c, or b+c): ** Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception ** Placement of an intrauterine device (IUD) or intrauterine system (IUS) ** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
• In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment
• Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after stopping midostaurin medication; they should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
• Ability to understand and the willingness to sign a written informed consent document
• The patients' last dose of chemotherapy must be at least 3 weeks prior to initiation of study therapy

Exclusion Criteria

• Participants who have had pelvic radiotherapy prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Participants may not be receiving any other investigational agents; patients may not be receiving any other treatment for their rectal cancer during study participation and within 30 days prior to study treatment
• Participants with known metastases
• History of known radiation sensitivity syndrome
• History of inflammatory bowel disease (Crohn's or ulcerative colitis)
• Active scleroderma or calcinosis cutis with features of Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with radiation
• Individuals with a history of a different malignancy are ineligible except for the following circumstances; individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; individuals with the following cancers are eligible if diagnosed and treated for cure within the past 5 years: cervical cancer in situ; basal cell or squamous cell carcinoma of the skin; or carcinoma in situ of the bladder, vocal cord, or breast
• Patients with a known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
• Patients who have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of day 1
• Patients with any pulmonary infiltrate including those suspected to be of infectious origin; in particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray are not eligible until pulmonary infiltrates have completely resolved
• Screening electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec
• Patients with congenital long QT syndrome
• History or presence of sustained ventricular tachycardia
• Any history of ventricular fibrillation or torsades de pointes
• Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm)
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Patients with myocardial infarction or unstable angina < 6 months prior to starting study drug
• Congestive heart failure (CHF) New York (NY) Heart Association class III or IV
• Patients with an ejection fraction < 50% assessed by multigated acquisition scan (MUGA) or echocardiogram (ECHO) scan within 7 days of day 1