Heated Chemotherapy Solution (Hyperthermic Intraperitoneal Chemotherapy) Using Mitomycin-C or Melphalan in Treating Patients with Colorectal Peritoneal Carcinomatosis Undergoing Surgery
- Ability to understand and the willingness to sign a written informed consent
- Peritoneal surface disease (PSD) due to colorectal cancer or invasive adenocarcinoma of the appendix
- No clear evidence of systemic metastases
- No prior CRS-HIPEC treatment
- Patient has a planned complete macroscopic cytoreduction (CC0) * NOTE: randomization occurs before surgery; if, during surgery, the principal investigator (PI)/sub investigator (Sub-I) discerns that all disease cannot be removed surgically, HIPEC will not be performed, and the participant will be removed from the study. If participant is removed from the study, PI / surgeon will decide if standard of care surgery will proceed
- Eastern Cooperative Oncology Group (ECOG) 0 – 2
- Medically fit to undergo complex major abdominal surgery, as determined by examination by PI/Sub-Is
- Medically fit to receive systemic chemotherapy, as determined by examination by PI/Sub-Is
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x institutional upper limit of normal
- Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SPGT]) =< 2.5 x institutional upper limit of normal
- Creatinine 1.5 X institutional upper limit of normal
- Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Men of child-bearing potential must not donate sperm while on this study and for 90 days after the study treatment (surgery with HIPEC) * NOTE: Acceptable forms of birth control are listed below: ** One Barrier method (cervical cap with spermicide plus male condom; diaphragm with spermicide plus male condom) PLUS ** Hormonal method (oral contraceptives, implants, or injections) or an intrauterine device (e.g., Copper-T)
- Current or anticipated use of other investigational agents while participating in this study
- Patient has received systemic chemotherapy or radiotherapy within 4 weeks prior to study enrollment
- Patient has not recovered sufficiently (PI will judge patient recovery status) from adverse events due to agents administered more than 4 weeks prior to enrollment on this study
- Patient has history of or currently has non-peritoneal surface metastatic disease in addition to peritoneal surface malignancy
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to mitomycin-C or melphalan
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, life-threatening cardiac arrhythmia, severe pulmonary disease, uncontrolled diabetes, severe kidney disease or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants
- Patient actively being treated for other malignancy (current active treatment of early stage squamous or basal cell carcinomas of the skin is allowed, excluding treatment with other investigational agents and systemic chemotherapy or radiotherapy)
I. To compare morbidity and mortality after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) utilizing mitomycin (mitomycin-C) versus melphalan using the Comprehensive Complication Index (CCI) score.
I. To compare peritoneal surface disease-free survival after CRS-HIPEC utilizing mitomycin-C versus melphalan.
II. To compare disease-free survival after CRS-HIPEC utilizing mitomycin-C versus melphalan.
III. To compare overall survival after CRS-HIPEC utilizing mitomycin-C versus melphalan.
I. To identify clinical correlations between treatment arms and primary or secondary endpoints.
II. To identify molecular correlations between treatment arms and primary or secondary endpoints.
III. To identify correlations between SigNatera biomarker status and circulating tumor cells (CTCs) and secondary endpoints of the study.
IIIa. To evaluate the prognostic impact of SigNatera by correlating SigNatera status and peritoneal disease-free survival (DFS)
IIIb. To describe DFS and overall survival (OS) by SigNatera status
IIIc. To describe time to disease recurrence by SigNatera vs CTC changes vs carcinoembryonic antigen (CEA) vs imaging studies.
OUTLINE: During standard of care cytoreductive surgery, patients are randomized to 1 of 2 arms.
ARM I: Patients receive hyperthermic intraperitoneal chemotherapy with mitomycin over 90 minutes in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive hyperthermic intraperitoneal chemotherapy with melphalan over 90 minutes in the absence of disease progression or unacceptable toxicity.
After completion of study treatment patients are followed up for 1-3 weeks, every 3 months for up to 5 years, and then annually thereafter.
Trial Phase Phase II
Trial Type Treatment
University of Kansas Cancer Center
Mazin Francis Al-kasspooles
- Primary ID IIT-2016-MA-GI-MelphVMitC-HIPE
- Secondary IDs NCI-2019-02499
- Clinicaltrials.gov ID NCT03073694