This study is to test escalating doses of intraperitoneal (IP) oxaliplatin in conjunction with systemic bevacizumab and capecitabine in patients with Peritoneal Carcinomatosis (PC) from either appendiceal or colorectal adenocarcinoma that have been adequately cytoreduced and have undergone a peritoneal scan demonstrating patency of at least one of the intraperitoneal ports that were placed at the time of debulking.
Active, not recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| Intraperitoneal Oxaliplatin | Eloxatin | Dose Level 1 |
| Bevacizumab | Avastin | Dose Level 1 |
| Capecitabine | Xeloda | Dose Level 1 |
- To determine the maximum tolerated dose of IP oxaliplatin with systemic intravenous
bevacizumab and oral capecitabine after adequate surgical debulking and peritoneal scan
documenting function of intraperitoneal ports in patients with peritoneal carcinomatosis
of appendiceal or colorectal etiology.
- To assess the safety and tolerability of repeated delayed intraperitoneal chemotherapy
with oxaliplatin and systemic intravenous bevacizumab and oral capecitabine after
adequate surgical debulking and peritoneal scan documenting function of intraperitoneal
ports in patients with peritoneal carcinomatosis of appendiceal or colorectal etiology.
- To describe the progression rate, progression-free survival and overall survival in
patients treated with this regimen.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Dose Level 1 | Experimental | Intraperitoneal oxaliplatin 25 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long. |
|
| Dose Level 2 | Experimental | Intraperitoneal oxaliplatin 50 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long. |
|
| Dose Level 3 | Experimental | Intraperitoneal oxaliplatin 65 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long. |
|
| Dose Level 4 | Experimental | Intraperitoneal oxaliplatin 85 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long. |
|
| Dose Level 5 | Experimental | Intraperitoneal oxaliplatin 100 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long. |
|
Inclusion Criteria:
- Histological Diagnosis: Patients must have a histologically documented peritoneal
carcinomatosis from either colorectal or appendiceal adenocarcinoma.
- Prior Surgical Debulking: Patients must have undergone debulking surgery with
peritonectomy and have been allowed at least 4 weeks to recover prior to receiving
chemotherapy.
- Port Placement: Intraperitoneal ports may be placed during or at any time separate
from surgical debulking. Provided the patient has been allowed at least 4 weeks to
recover from surgical debulking, no additional recovery time is required for port
placement.
- Active port: Patients must undergo a peritoneal scan documenting at least one working
intraperitoneal port prior to receiving chemotherapy.
- Patients may have received prior chemotherapy.
- Age: Patients must be ≥18 years of age. Because no dosing or toxicity data are
currently available on the use of oxaliplatin in patients <18 years of age.
- Performance Status: (Eastern cooperativeOncology Group) ECOG 0-2.
- Recovery from Intercurrent Illness: Patients must have recovered from uncontrolled
intercurrent illness including, but not limited to, ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmias.
- Informed Consent: All patients must be consented prior to chemotherapy. The patient
should not have any serious medical of psychiatric illness that would prevent either
the giving of informed consent or the receipt of treatment.
- Hematological Status:
- absolute neutrophil count ≥1,500/mm³
- platelet count ≥100,000/mm³
- hemoglobin ≥8 g/dl.
- Hepatic function:
- Total bilirubin must be <2X the institutional upper limit of normal (ULN)
- Transaminases (SGOT and/or SGPT) must be ≤3X the institutional upper limit of
normal (ULN)
- Alkaline phosphatase must be ≤4X the institutional upper limit of normal (ULN)
- Renal Function: Patients must have adequate renal function prior to chemotherapy
defined as serum creatinine ≤ 2.0 mg/dl or creatinine clearance ≥60 ml.min/1.73 m² for
patients with creatinine levels above 2.0 mg/dl.
Exclusion Criteria:
- Pregnant or breast feeding: For all sexually active patients, the use of adequate
contraception (hormonal or barrier method of birth control) will be required during
therapy, prior to study entry, and for the duration of study participation.
Non-pregnant status will be determined in all women of childbearing potential.
- Prior history of hypersensitivity reactions to oxaliplatin, bevacizumab, 5-FU or
capecitabine.
- Gastrointestinal ailments that may alter the absorption of oral medications (i.e.
bowel obstruction, short-gut syndrome).
- Patients receiving antiretroviral therapy Highly Active Anti Retroviral Treatment
(HAART) for HIV infection are excluded from the study because of possible
pharmacokinetic interactions. Appropriate studies will be undertaken in patients
receiving HAART therapy, when indicated.
- Patients with Grade 2 or higher peripheral neuropathy.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | To determine the maximum tolerated dose of IP oxaliplatin with systemic intravenous bevacizumab and oral capecitabine after surgical debulking and peritoneal scan documenting functional of intraperitoneal ports in patients with peritoneal carcinomatosis |
| Time Frame: | Completion of enrollment (approximately 8 years) |
| Safety Issue: | |
| Description: | -Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Washington University School of Medicine |
November 5, 2020
