Carcinoma of the AppendixPhase 1NCT00458809
Intraperitoneal Hyperthermic Perfusion With Oxaliplatin in Treating Patients With Stage IV Peritoneal Cancer Due to Appendix Cancer or Colorectal Cancer
A Phase 1 study testing oxaliplatin in people with Carcinoma of the Appendix and Colorectal Cancer, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hyperthermia therapy kills tumor cells by heating them to several degrees above normal body temperature. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Carcinoma of the Appendix, Colorectal Cancer, Primary Peritoneal Cavity Cancer
- What is being tested?
- oxaliplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Nov 2007
- Phase
- Phase 1
- 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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed colorectal or appendiceal cancer
- Stage IV disease
- Peritoneal surface dissemination of disease (peritoneal carcinomatosis)
- Measurable disease according to RECIST criteria
- No active CNS metastases
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
- Bilirubin ≤ 1.5 mg/dL
- Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
- AST and ALT ≤ 3 times ULN
- No active infection or fever ≥ 101.3°F within the past 3 days
- No other malignancy within the past 5 years except curatively treated basal cell skin cancer, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate-specific antigen of < 1.0 mg/dL on 2 successive evaluations, ≥ 3 months apart, with the last evaluation within the past 4 weeks
- No peripheral neuropathy ≥ grade 2
- No other medical condition, mental illness, or substance abuse that, in the opinion of the principal investigator, would preclude study compliance
- No known hypersensitivity to any component of oxaliplatin
- No known HIV positivity
- No hepatitis B or C positivity (active, previously treated, or both)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients and their partners must use effective contraception during and for 90 days after completion of study treatment
PRIOR CONCURRENT THERAPY:
- Recovered from prior surgery, radiotherapy, and other anticancer therapies
- More than 30 days since prior and no other concurrent investigational therapy
- No prior radiotherapy to > 25% of bone marrow
- No prior allogeneic stem cell transplantation
- No concurrent antiretroviral therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1096
About this study
Official title: A Phase I Evaluation of Intraperitoneal Hyperthermic Chemoperfusion With Oxaliplatin for Peritoneal Surface Disemmination of Appendiceal and Colorectal Cancer
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hyperthermia therapy kills tumor cells by heating them to several degrees above normal body temperature. Adding chemotherapy to hyperthermia and infusing it directly into the abdomen may kill more tumor cells. Giving this treatment after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal hyperthermic perfusion with oxaliplatin in treating patients with stage IV peritoneal cancer due to appendix cancer or colorectal cancer.
Read the detailed description
OBJECTIVES:
- Determine the toxicity of intraperitoneal hyperthermic chemoperfusion with oxaliplatin in patients with stage IV peritoneal surface malignancies from primary colorectal or appendiceal cancer.
- Determine the pharmacokinetics of this drug in perfusate, normal peritoneum, and peritoneal surface tumors in these patients.
- Evaluate the expression of proteins involved in the apoptotic and stress-inducible heat shock protein pathways (e.g., Fas, TRAIL, DISC components [FADD, TRADD, FLIP, and caspase 8], mitochondrial proteins [Bax, Bak, Bcl-2, Bcl-X_L], and heat shock proteins [HSPs 27, 40, 70 and 90]) before and after drug therapy.
OUTLINE: This is a nonrandomized, open-label, dose-escalation study.
Patients undergo gross tumor resection on day 1. After tumor debulking, patients receive oxaliplatin over 2 hours by intraperitoneal hyperthermic chemotherapy (IPHC).
Cohorts of 3-6 patients in each stratum receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Patients undergo blood and tissue sampling before and after IPHC for pharmacokinetic studies and for evaluation of proteins involved in apoptosis and heat-shock-mediated cell death (e.g., Fas, TRAIL, FADD, TRADD, FLIP, caspase 8, Bax, Bak, Bcl-X, and heat shock proteins 27, 40, 70, and 90).
After completion of study treatment, patients are followed periodically for at least 1 year.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
- Being tested
- oxaliplatin
- Keywords
- recurrent colon cancer, stage IV colon cancer, carcinoma of the appendix, recurrent rectal cancer, stage IV rectal cancer, primary peritoneal cavity cancer
- Medical subject headings
- Appendiceal Neoplasms, Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oxaliplatinDrug
Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin
| Study group | Role | What they receive |
|---|---|---|
| Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2 | Experimental | Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2 Receives: Drug: oxaliplatin |
| Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2 | Experimental | Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2 Receives: Drug: oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
Maximum tolerated dose will be determined by the absence of dose limiting toxicites (serious adverse events related to Oxaplatin dosing within 18 days of administration)
Measured: 18 days
Secondary outcomes (2)
Pharmacokinetics
Evaluation of the pharmacokinetics of oxaliplatin in perfusate, normal peritoneum, and peritoneal surface tumors during intraperitoneal hyperthermic chemoperfusion
Measured: day of surgery (day one)
Change in the phenotypic expression of proteins involved in the apoptotic and heat-stress inducible pathways
Analysis of the expression of proteins involved in the apoptotic and stress-inducible heat shock protein pathways before and after intraperitoneal hyperthermic chemoperfusion with oxaliplatin. These proteins shall include cellular levels of Fas and TRAIL, components of the DISC (FADD, TRADD, FLIP, and Caspase 8), mitochondrial proteins (Bax, Bak, Bcl-2, and Bcl-XL), and the heat shock protein family (HSPs 27, 40, 70, and 90).
Measured: Day of surgery (day one)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2007 (estimated)
- Study startMar 2007
- Primary completionNov 2007
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma of the AppendixStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- John H. Stewart, MD, Study chair, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00458809
- Sponsor's protocol ID
- CDR0000540283
- Other IDs
- P30CA012197, CCCWFU-59106, CCCWFU-IRB00000847, CCCWFU-59106 IPHC
- Status last verified
- Aug 2018
- First submitted
- 9 Apr 2007
- Last updated
- 9 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Stewart JH 4th, Shen P, Russell G, Fenstermaker J, McWilliams L, Coldrun FM, Levine KE, Jones BT, Levine EA. A phase I trial of oxaliplatin for intraperitoneal hyperthermic chemoperfusion for the treatment of peritoneal surface dissemination from colorectal and appendiceal cancers. Ann Surg Oncol. 2008 Aug;15(8):2137-45. doi: 10.1245/s10434-008-9967-1. Epub 2008 May 21.
PubMed 18493824
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Evaluation of Intraperitoneal Hyperthermic Chemoperfusion With Oxaliplatin for Peritoneal Surface Disemmination of Appendiceal and Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00458809
- Acronym / sponsor ID
- CDR0000540283
- Keywords
- recurrent colon cancer, stage IV colon cancer, carcinoma of the appendix, recurrent rectal cancer, stage IV rectal cancer, primary peritoneal cavity cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2007
- Primary completion
- Nov 2007 (actual)
- Study completion
- Nov 2007 (actual)
- First posted
- 11 Apr 2007 (estimated)
- 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.
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hyperthermia therapy kills tumor cells by heating them to several degrees above normal body temperature. Adding chemotherapy to hyperthermia and infusing it directly into the abdomen may kill more tumor cells. Giving this treatment after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal hyperthermic perfusion with oxaliplatin in treating patients with stage IV peritoneal cancer due to appendix cancer or colorectal cancer.
Detailed description
OBJECTIVES:
- Determine the toxicity of intraperitoneal hyperthermic chemoperfusion with oxaliplatin in patients with stage IV peritoneal surface malignancies from primary colorectal or appendiceal cancer.
- Determine the pharmacokinetics of this drug in perfusate, normal peritoneum, and peritoneal surface tumors in these patients.
- Evaluate the expression of proteins involved in the apoptotic and stress-inducible heat shock protein pathways (e.g., Fas, TRAIL, DISC components [FADD, TRADD, FLIP, and caspase 8], mitochondrial proteins [Bax, Bak, Bcl-2, Bcl-X_L], and heat shock proteins [HSPs 27, 40, 70 and 90]) before and after drug therapy.
OUTLINE: This is a nonrandomized, open-label, dose-escalation study.
Patients undergo gross tumor resection on day 1. After tumor debulking, patients receive oxaliplatin over 2 hours by intraperitoneal hyperthermic chemotherapy (IPHC).
Cohorts of 3-6 patients in each stratum receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Patients undergo blood and tissue sampling before and after IPHC for pharmacokinetic studies and for evaluation of proteins involved in apoptosis and heat-shock-mediated cell death (e.g., Fas, TRAIL, FADD, TRADD, FLIP, caspase 8, Bax, Bak, Bcl-X, and heat shock proteins 27, 40, 70, and 90).
After completion of study treatment, patients are followed periodically for at least 1 year.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2 | Experimental | Drug: oxaliplatinIntraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2 |
| Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2 | Experimental | Drug: oxaliplatinIntraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2 |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| oxaliplatinIntraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin | Drug | Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2, Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2 |
Primary outcome
Maximum tolerated dose
Time frame: 18 days
Maximum tolerated dose will be determined by the absence of dose limiting toxicites (serious adverse events related to Oxaplatin dosing within 18 days of administration)
2 secondary outcomes
Pharmacokinetics
Time frame: day of surgery (day one)
Change in the phenotypic expression of proteins involved in the apoptotic and heat-stress inducible pathways
Time frame: Day of surgery (day one)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2018.
- Results publication: PubMed 18493824Stewart JH 4th, Shen P, Russell G, Fenstermaker J, McWilliams L, Coldrun FM, Levine KE, Jones BT, Levine EA. A phase I trial of oxaliplatin for intraperitoneal hyperthermic chemoperfusion for the treatment of peritoneal surface dissemination from colorectal and appendiceal cancers. Ann Surg Oncol. 2008 Aug;15(8):2137-45. doi: 10.1245/s10434-008-9967-1. Epub 2008 May 21.
Related trials for Carcinoma of the Appendix
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 1
Individual Response to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Histologies
Peritoneal Mesothelioma, Peritoneal Carcinomatosis
RecruitingPhase 3
Pressurized Intraperitoneal Aerosolized Chemotherapy With Mitomycin for the Treatment of Unresectable Appendix or Colorectal Cancer With Peritoneal Metastases, The IMPACT Trial
Metastatic Appendix Carcinoma, Metastatic Colorectal Carcinoma
Recruiting
Studying the PAGODA Algorithm for Chemotherapy Dose Changes to Prevent Unplanned Treatment Delays
Ampulla of Vater Carcinoma, Appendix Carcinoma
RecruitingPhase 4
Intraoperative Imaging of Gastrointestinal Malignancies Using Pafolacianine (CYTALUX™)
Gastrointestinal Cancer, Gastric Cancer
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.
John H. Stewart, MD study chair
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing oxaliplatin in people with Carcinoma of the Appendix and Colorectal Cancer, run by Wake Forest University Health Sciences 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?
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: finished, as of the sponsor's last update on 9 Aug 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (time frame: 18 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00458809, which also lists 1 linked publication.
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 Aug 2018.