Surgery and Oxaliplatin or Mitomycin C in Treating Patients With Tumors of the Appendix

A Multi-Center, Open-Label, Randomized Phase II Trial to Evaluate Hematologic Toxicities After HIPEC With Oxaliplatin or Mitomycin C in Patients With Appendiceal Tumors

This randomized phase II trial is studying the side effects and how well giving oxaliplatin or mitomycin C directly into the abdomen after surgery works in treating patients with tumors of the appendix. Drugs used in chemotherapy, such as oxaliplatin and mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Heating a chemotherapy solution and infusing it directly into the abdomen may kill more tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

Study Overview

• Status: Completed
• Conditions: Primary Peritoneal Cavity Cancer; Carcinoma of the Appendix
• Intervention / Treatment: Other: quality-of-life assessment; Procedure: therapeutic conventional surgery; Drug: mitomycin C; Drug: hyperthermic intraperitoneal chemotherapy; Drug: oxaliplatin

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the toxicity profiles within 4 weeks of surgery of oxaliplatin and mitomycin C delivered via Hyperthermic Intraperitoneal Chemotherapy in patients with peritoneal surface malignancies from primary appendiceal tumors.

SECONDARY OBJECTIVES:

I. To compare the time to progression in patients treated with oxaliplatin vs. mitomycin C delivered via Hyperthermic Intraperitoneal Chemotherapy for surface malignancies from primary appendiceal tumors.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo surgical cytoreduction and receive mitomycin C by hyperthermic intraperitoneal chemotherapy (HIPEC).

Arm II: Patients undergo surgical cytoreduction and receive oxaliplatin by HIPEC.

After completion of study treatment, patients are followed up at 6, 12, 18, 24, 30, and 36 months.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed peritoneal surface malignancies from primary appendiceal tumors
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count >= 1,500/mcL
• Platelets >=100,000/mcL
• Total bilirubin =< 1.5 mg/dL
• Creatinine =< 2.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 X institutional upper limit of normal
• Alkaline phosphatase =< 3 X institutional upper limit of normal
• Patients must be recovered from both the acute and late effects of any prior surgery, radiotherapy, or other antineoplastic therapy
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or double-barrier method of birth control; abstinence) for the duration of study participation and for 90 days following HIPEC
• Ability to understand and the willingness to sign a written informed consent document (either directly or via a legally authorized representative)
• Participants who have received oxaliplatin during prior systemic chemotherapy regimens are eligible for enrollment in this protocol

Exclusion Criteria:

• Patients with an active infection or with a fever >= 101.3 degrees Fahrenheit (F) within 3 days of the first scheduled day of protocol treatment
• Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of HIPEC (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication)
• Patients with carcinoid tumors
• Patients with active central nervous system (CNS) metastases
• Patients with known hypersensitivity to any of the components of oxaliplatin or mitomycin C
• History of prior malignancy within the past 5 years, except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate-specific antigen (PSA) of < 1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry
• Patients who received radiotherapy to more than 25% of their bone marrow
• 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/nursing women are excluded from this study because oxaliplatin is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with oxaliplatin, breastfeeding should be discontinued if the mother is treated with oxaliplatin or mitomycin C
• Known human immunodeficiency virus (HIV), hepatitis B or C-positive patients (active, previously treated or both)
• Peripheral neuropathy >= grade 2
• History of allogenic transplant
• History of prior HIPEC
• Evidence of metastatic disease outside of the abdomen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (mitomycin C); Patients undergo surgical cytoreduction and receive mitomycin C by HIPEC.	Other: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Procedure: therapeutic conventional surgery; Undergo surgery; Drug: mitomycin C; Given by HIPEC; Other Names: MITO; Mitocin-C; MTC; MITC; MITO-C; Drug: hyperthermic intraperitoneal chemotherapy; Undergo HIPEC
Experimental: Arm II (oxaliplatin); Patients undergo surgical cytoreduction and receive oxaliplatin by HIPEC.	Other: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Procedure: therapeutic conventional surgery; Undergo surgery; Drug: hyperthermic intraperitoneal chemotherapy; Undergo HIPEC; Drug: oxaliplatin; Given by HIPEC; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; L-OHP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Difference in the Number of Grade 3 or 4 Hematologic Toxicities (Leukopenia, Thrombocytopenia, and Neutropenia) Between the Mitomycin C and Oxaliplatin Treatments	If a patient has a grade 3 or 4 standard hematologic toxicity (leukopenia, thrombocytopenia, and neutropenia), the patient will be considered to be an event. The observed rates of the 2 treatments will be the primary outcome, and the rates will be analyzed using a 2-sided chi-square test.	Within 4 weeks of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Difference in Percentage of Disease-free Survival Between the Two Treatment Arms up to 3 Years		Time to first progression unless the patient's resection status is R2b or 2c, regardless of toxicity or response to study drug, assessed up to 3 years
The Difference in Percentage of Overall Survival Between the Two Treatment Arms up to 3 Years		Interval between surgery and death or date of last contact, assessed up to 3 years
Quality of Life as Assessed by Functional Assessment of Cancer Therapy: General (FACT-G)	The FACT-G (Functional Assessment of Cancer Therapy - General) consists of 27 core items assessing patient well-being in four components: Physical (7 items), Social/Family (7 items), Emotional (6 items), and Functional (7 items). Items are rated on a five-point scale: 0-"not at all", 1- "a little bit", 2-"somewhat", 3- "quite a bit" and 4-"very much". The score of each component is the mean times the number of items in the component. The range of the physical, social/family, and functional components I 0-28 and the range of the emotional component is 0-24. The sum of the component scores creates the overall score which has a range of 0-108. For all component scores and overall score, the higher the score the better the QOL.	Throughout study completion, up to 3 years

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Edward Levine, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: April 17, 2012
• First Submitted That Met QC Criteria: April 17, 2012
• First Posted (Estimate): April 19, 2012

Study Record Updates

• Last Update Posted (Actual): July 3, 2018
• Last Update Submitted That Met QC Criteria: June 29, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Peritoneal Diseases; Digestive System Neoplasms; Abdominal Neoplasms; Peritoneal Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Oxaliplatin; Mitomycins; Mitomycin
• Other Study ID Numbers: IRB00009326; NCI-2009-00947 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CCCWFU 59109 (Other Identifier: Wake Forest University Health Sciences)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No