A Phase I/II Study of the Safety and Biological Activity of Intraperitoneal EGEN-001 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) Administered Alone and in Combination With Standard Chemotherapy in Colorectal Peritoneal Carcinomatosis Patients Who Had Previously Received Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Therapy
- At least 18 years of age (or minimum legal age and competency to provide voluntary
written informed consent for study participation) and no more than 80 years of age.
- Patients must have colorectal carcinoma (including appendiceal) with metastases
limited to peritoneal cavity. Histological documentation of the original primary
tumor is required via pathology report.
- Patients must have completed surgical debulking + hyperthermic intraperitoneal
chemotherapy (mitomycin) and have had a peritoneal catheter inserted 6-8 weeks before
beginning infusion with IP EGEN-001 and must have post-debulking peritoneal cancer
index (PCI) of <2. Patients do not have to have measurable metastases by RECIST
criteria following surgical debulking.
- Patients may have received previous systemic chemotherapy for colorectal cancer, but
this is not required.
- Patients must have an ECOG Performance Status of 0, 1, or 2.
- Any other prior therapy directed at the malignant tumor, including biological and
immunologic agents, must be discontinued at least three weeks prior to enrollment.
- Patients should be free of active infection requiring antibiotics (with the exception
of uncomplicated UTI.)
- Patients must have adequate:
1. Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to
1,500/mcl, equivalent to the Active Version of the NCI Common Terminology
Criteria (CTCAE) grade 1. Platelets greater than or equal to 100,000/mcl.
2. Renal function: creatinine less than or equal to 1.5 x institutional upper limit
normal (ULN), per the Active Version of the NCI CTCAE grade 1.
3. Hepatic function: Bilirubin less than or equal to 1.5 x ULN (per the Active
Version of the NCI CTCAE grade 1). SGOT (AST) less than or equal to 3 x ULN (per
the Active Version of the NCI CTCAE grade 1) and alkaline phosphatase less than
or equal to 2.5 x ULN (per the Active Version of the NCI CTCAE grade 1).
4. Neurologic function: Neuropathy (sensory and motor) less than or equal to the
Active Version of the NCI CTCAE grade 1.
- Patients must have signed an approved informed consent and authorization permitting
release of personal health information.
- Women of childbearing potential must have a negative pregnancy test prior to the
study entry and be practicing an effective form of contraception. Female partners of
childbearing potential of male patients must also use an effective form of
contraception. Contraception must be used for 90 days following the last dose of
- Patients who have had prior therapy with EGEN-001 or IL-12.
- Prior radiation therapy to the abdomen or pelvis less than 6 months prior to entering
- Patients with a serious uncontrolled medical illness or disorder or active infection
within four weeks of study entry.
- Patients with any condition/anomaly that would interfere with the appropriate
placement of the IP catheter for study drug administration including: intestinal
dysfunction or suspected extensive adhesions from prior history or finding at
- Metastases beyond the peritoneal cavity including liver, lung or retroperitoneal
- History of other malignancy other than non-melanoma skin cancer or in situ cervical
carcinoma within the last 5 years.
- The patient is pregnant or lactating.
- The patient has taken an investigational agent in the preceding 4 weeks.
- Patients with a history of HIV, hepatitis B or hepatitis C.
- Patients who require treatment with pharmacologic doses of systemic steroids;
replacement doses, topical, inhalation and ophthalmic steroid use is permitted.
- Patients who are allergic to any of the components of EGEN-001.