Heated Chemotherapy Solution (Hyperthermic Intraperitoneal Chemotherapy) Using Mitomycin-C or Melphalan in Treating Patients with Colorectal Peritoneal Carcinomatosis Undergoing Surgery

Status: Active

Description

This phase II trial studies how well hyperthermic intraperitoneal chemotherapy using mitomycin-C or melphalan works in treating patients with tumors that develop in the lining of the abdomen (peritoneal carcinomatosis) due to colorectal cancer. Drugs used in chemotherapy, such as mitomycin-C and melphalan, 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. Giving heated chemotherapy drugs directly into the abdomen during surgery may kill more tumor cells. This study may help doctors see if one of the chemotherapy drugs (mitomycin-C or melphalan) is safer or more effective than the other in helping patients with peritoneal carcinomatosis live longer.

Eligibility Criteria

Inclusion Criteria

  • Ability to understand and the willingness to sign a written informed consent
  • Peritoneal surface disease (PSD) due to colorectal cancer or high-grade appendiceal cancer
  • No clear evidence of systemic metastases
  • No prior CRS-HIPEC treatment
  • Patient has a planned complete macroscopic cytoreduction (CC0) * NOTE: randomization occurs during surgery and not before; if, during surgery, the principal investigator (PI)/substitute investigator (SubI) discerns that all disease cannot be removed surgically, the participant will be considered a “screen failure”, 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
  • Recorded American Society of Anesthesiologists (ASA) classification – as determined by the anesthesiologist (particular value not required – only recording of the classification is required)
  • 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 within normal institutional limits
  • 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)

Exclusion Criteria

  • 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)

Locations & Contacts

Kansas

Kansas City
University of Kansas Cancer Center
Status: Active
Contact: Mazin Francis Al-kasspooles
Phone: 913-588-6568
Email: mal-kasspooles@kumc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

EXPLORATORY OBJECTIVES:

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.

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 & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Kansas Cancer Center

Principal Investigator
Mazin Francis Al-kasspooles

Trial IDs

Primary ID IIT-2016-MA-GI-MelphVMitC-HIPE
Secondary IDs NCI-2019-02499
Clinicaltrials.gov ID NCT03073694