Cancer, AppendicealPhase 2NCT03073694
Comparing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) Using Mitomycin-C Versus Melphalan for Colorectal Peritoneal Carcinomatosis
A Phase 2 study testing Mitomycin c and Melphalan in people with Cancer, Appendiceal and ColoRectal Cancer, run by University of Kansas Medical Center at 1 site in United States.
Trial summary
The purpose of this trial is to compare the morbidity and mortality of CRS-HIPEC using mitomycin-C versus melphalan for colorectal peritoneal carcinomatosis. Morbidity and mortality will measured using the Comprehensive Complication Index (CCI) score, Common terminology criteria for adverse events (CTCAE version… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cancer, Appendiceal, ColoRectal Cancer
- What is being tested?
- Mitomycin c and Melphalan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jul 2017to Jul 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 CC0 (Complete Macroscopic Cytoreduction (visual)) cytoreduction - NOTE: randomization occurs during surgery and not before; if, during surgery, the PI/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.
- Age 18 - 75
Show all 32Show fewer
- ECOG (Eastern Cooperative Oncology Group) Score 0 - 2
- Recorded ASA (American Society of Anesthesiologist Classification) 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.
- Adequate organ and marrow function as defined below:
- leukocytes ≥ 3,000/mcL (microliter)
- absolute neutrophil count ≥ 1,500/mcL
- platelets ≥ 100,000/mcL
- total bilirubin within normal institutional limits
- AST (Aspartate aminotransferase) (SGOT [Serum Glutamic Oxaloacetic Transaminase]) ≤ 2.5 X institutional upper limit of normal
- ALT (Alanine Aminotransferase) (SPGT [Serum Glutamic Pyruvic Transaminase]) ≤ 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).
- Exclusion Criteria Participants meeting any of the exclusion criteria at baseline will be excluded from study participation.
- 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).
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
The University of Kansas Medical Center
Westwood, Kansas, 66205
Steve Williamson, MD, 913-588-3808, SWILLIAM@kumc.edu
About this study
Official title: Phase II Single-Blind Randomized Trial Comparing Morbidity of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) Using Mitomycin-C Versus Melphalan for Colorectal Peritoneal Carcinomatosis
The purpose of this trial is to compare the morbidity and mortality of CRS-HIPEC using mitomycin-C versus melphalan for colorectal peritoneal carcinomatosis. Morbidity and mortality will measured using the Comprehensive Complication Index (CCI) score, Common terminology criteria for adverse events (CTCAE version 4.03), and the Clavien-Dindo Classification.
Read the detailed description
BACKGROUND: Peritoneal dissemination of cancer (peritoneal carcinomatosis) from gastrointestinal malignancies, meaning tumor deposits along the inside abdominal or pelvic wall and surfaces of the intestines and organs, has historically been considered a terminal disease. Although peritoneal surface tumors can respond to systemic therapy as a sole form of treatment, patient survival remains poor and cure is considered impossible.
A plasma-peritoneal barrier makes systemic therapy relatively ineffective against peritoneal surface disease. In the 1990's, cytoreductive surgery and hyperthermic intraperitoneal therapy (CRS-HIPEC) began to be popularized as a more effective treatment.
Hyperthermic intraperitoneal chemotherapy has several advantages. High-dose chemotherapy can be used due to the plasma-peritoneal barrier resulting in little absorption into the blood stream. Hyperthermia itself has cytotoxic effects and can increase the depth of tumor penetration by the chemotherapeutic agent up to 3 mm and moreover can potentiate its antineoplastic effects. Although CRS-HIPEC has been considered standard treatment for ruptured appendiceal neoplasms and primary peritoneal mesothelioma, in the past decade its indications have broadened to other peritoneal surface malignant processes.
Historically, morbidity and mortality associated with CRS-HIPEC was considerably higher than other complex operations, and thus its use was often discouraged. However, in recent times, especially in high-volume centers, morbidity and mortality has drastically improved. Due to recent improvements in mortality after major surgical interventions, including HIPEC, the focus has shifted toward other endpoints besides efficacy, such as morbidity, quality of life and cost.
While HIPEC is universally felt to be a vital component after cytoreductive surgery, there is a lack of consensus on the optimal regimen, especially the chemotherapeutic agent that should be used. In the United States, the most commonly used agent during HIPEC is mitomycin-C, however, it remains unknown if mitomycin-C is the optimal drug to use with regards to toxicity and survival.
Randomized prospective studies are needed comparing the toxicity and effectiveness of HIPEC with mitomycin-C to other agents.
OBJECTIVE: To compare morbidity and mortality after CRS-HIPEC utilizing mitomycin-C versus melphalan.
METHODS: In this study, patients will be randomized to one of two treatment arms: Arm 1.) Mitomycin-C initial dose of 15 mg/m2, 45 minutes into the perfusion a maintenance dose of 5 mg/m2 will be administered; or Arm 2): Melphalan 60 mg/m2 45 minutes into the perfusion. Morbidity will be measured during immediate and short-term surgical recovery (up to 90 days post-hospital discharge). Mortality will be measured beginning with the date of surgery and ending with the date of participant death.
- Conditions
- Cancer, Appendiceal, ColoRectal Cancer
- Being tested
- Mitomycin c, Melphalan
- Keywords
- Peritoneal Surface Disease, mitomycin-c, melphalan, Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC), Peritoneal Carcinomatosis
- Medical subject headings
- Appendiceal Neoplasms, Colorectal Neoplasms, Peritoneal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitomycin cDrug
Also called Mutamycin, MTC
Mitomycin-c will be given to participants in Treatment Arm 1 as a one-time, intraoperative, intravenous administration for a duration of 90 minutes. 45 minutes into the perfusion, a maintenance dose will be administered.
MelphalanDrug
Also called Alkeran
Melphalan will be given to participants in Treatment Arm 2 as a one-time, intraoperative, intravenous administration for a duration of 90 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Mitomycin C Group | Active comparator | Mitomycin-C initial dose of 15 mg/m2 (milligrams per meter squared) 45 minutes into the perfusion, a maintenance dose of 5 mg/m2 will be administered. Receives: Drug: Mitomycin c |
| Melphalan Group | Experimental | Melphalan 60 mg/m2 (milligrams per meter squared) 45 minutes into the perfusion. Receives: Drug: Melphalan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comprehensive Complication Index (CCI) score.
CCI will be evaluated using the following data: morbidity, mortality.
Measured: Every 3 months until Year 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2017
- Study start14 Jul 2017
- Primary completionJul 2024 (estimated)
- Study completionJul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer, AppendicealStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mazin Al-kasspooles, MD, Principal investigator, The University of Kansas - Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03073694
- Sponsor's protocol ID
- IIT-2016-MAGIMelphVMitCHIPEC
- Status last verified
- Jun 2023
- First submitted
- 9 Feb 2017
- Last updated
- 9 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Single-Blind Randomized Trial Comparing Morbidity of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) Using Mitomycin-C Versus Melphalan for Colorectal Peritoneal Carcinomatosis
- ClinicalTrials.gov ID
- NCT03073694
- Acronym / sponsor ID
- IIT-2016-MAGIMelphVMitCHIPEC
- Conditions
- Cancer, Appendiceal, ColoRectal Cancer
- Keywords
- Peritoneal Surface Disease, mitomycin-c, melphalan, Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC), Peritoneal Carcinomatosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Study start
- 14 Jul 2017 (actual)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Jul 2025 (estimated)
- First posted
- 8 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to compare the morbidity and mortality of CRS-HIPEC using mitomycin-C versus melphalan for colorectal peritoneal carcinomatosis. Morbidity and mortality will measured using the Comprehensive Complication Index (CCI) score, Common terminology criteria for adverse events (CTCAE version 4.03), and the Clavien-Dindo Classification.
Detailed description
BACKGROUND: Peritoneal dissemination of cancer (peritoneal carcinomatosis) from gastrointestinal malignancies, meaning tumor deposits along the inside abdominal or pelvic wall and surfaces of the intestines and organs, has historically been considered a terminal disease. Although peritoneal surface tumors can respond to systemic therapy as a sole form of treatment, patient survival remains poor and cure is considered impossible.
A plasma-peritoneal barrier makes systemic therapy relatively ineffective against peritoneal surface disease. In the 1990's, cytoreductive surgery and hyperthermic intraperitoneal therapy (CRS-HIPEC) began to be popularized as a more effective treatment.
Hyperthermic intraperitoneal chemotherapy has several advantages. High-dose chemotherapy can be used due to the plasma-peritoneal barrier resulting in little absorption into the blood stream. Hyperthermia itself has cytotoxic effects and can increase the depth of tumor penetration by the chemotherapeutic agent up to 3 mm and moreover can potentiate its antineoplastic effects. Although CRS-HIPEC has been considered standard treatment for ruptured appendiceal neoplasms and primary peritoneal mesothelioma, in the past decade its indications have broadened to other peritoneal surface malignant processes.
Historically, morbidity and mortality associated with CRS-HIPEC was considerably higher than other complex operations, and thus its use was often discouraged. However, in recent times, especially in high-volume centers, morbidity and mortality has drastically improved. Due to recent improvements in mortality after major surgical interventions, including HIPEC, the focus has shifted toward other endpoints besides efficacy, such as morbidity, quality of life and cost.
While HIPEC is universally felt to be a vital component after cytoreductive surgery, there is a lack of consensus on the optimal regimen, especially the chemotherapeutic agent that should be used. In the United States, the most commonly used agent during HIPEC is mitomycin-C, however, it remains unknown if mitomycin-C is the optimal drug to use with regards to toxicity and survival.
Randomized prospective studies are needed comparing the toxicity and effectiveness of HIPEC with mitomycin-C to other agents.
OBJECTIVE: To compare morbidity and mortality after CRS-HIPEC utilizing mitomycin-C versus melphalan.
METHODS: In this study, patients will be randomized to one of two treatment arms: Arm 1.) Mitomycin-C initial dose of 15 mg/m2, 45 minutes into the perfusion a maintenance dose of 5 mg/m2 will be administered; or Arm 2): Melphalan 60 mg/m2 45 minutes into the perfusion. Morbidity will be measured during immediate and short-term surgical recovery (up to 90 days post-hospital discharge). Mortality will be measured beginning with the date of surgery and ending with the date of participant death.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mitomycin C Group | Active comparator | Drug: Mitomycin cMitomycin-C initial dose of 15 mg/m2 (milligrams per meter squared) 45 minutes into the perfusion, a maintenance dose of 5 mg/m2 will be administered. |
| Melphalan Group | Experimental | Drug: MelphalanMelphalan 60 mg/m2 (milligrams per meter squared) 45 minutes into the perfusion. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- 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 CC0 (Complete Macroscopic Cytoreduction (visual)) cytoreduction - NOTE: randomization occurs during surgery and not before; if, during surgery, the PI/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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mitomycin cAlso: Mutamycin, MTCMitomycin-c will be given to participants in Treatment Arm 1 as a one-time, intraoperative, intravenous administration for a duration of 90 minutes. 45 minutes into the perfusion, a maintenance dose will be administered. | Drug | Mitomycin C Group |
| MelphalanAlso: AlkeranMelphalan will be given to participants in Treatment Arm 2 as a one-time, intraoperative, intravenous administration for a duration of 90 minutes. | Drug | Melphalan Group |
Primary outcome
Comprehensive Complication Index (CCI) score.
Time frame: Every 3 months until Year 2
CCI will be evaluated using the following data: morbidity, mortality.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mazin Al-kasspooles, MD principal investigator
The University of Kansas - Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mitomycin c and Melphalan in people with Cancer, Appendiceal and ColoRectal Cancer, run by University of Kansas Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mazin Al-kasspooles, MD (913-588-6568, mal-kasspooles@kumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comprehensive Complication Index (CCI) score. (time frame: Every 3 months until Year 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2023.