Phase I Trial Of Adenoviral Vector Delivery Of The Human Interleukin-12 cDNA By Intratumoral Injection In Patients With Metastatic Colorectal Cancer To The Liver
18 Years
N/A
Both
Colorectal Cancer, Metastatic Cancer
Trial Information
Phase I Trial Of Adenoviral Vector Delivery Of The Human Interleukin-12 cDNA By Intratumoral Injection In Patients With Metastatic Colorectal Cancer To The Liver
OBJECTIVES:
- Determine the toxicity and maximum tolerated dose of intratumoral adenoviral
vector-delivered interleukin-12 gene in patients with liver metastases secondary to
colorectal cancer .
- Determine the tumor response in patients treated with this regimen.
- Determine the immune response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study.
Patients receive ultrasound-guided intratumoral injections of adenoviral vector-delivered
interleukin-12 gene (ADV-hIL12) on day 1.
Cohorts of 3-6 patients receive escalating doses of ADV-hIL12 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.
Patients are followed at days 11, 15, 29, 43, and 57 and are then followed for survival
thereafter.
PROJECTED ACCRUAL: A total of 30-36 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed* colorectal adenocarcinoma metastatic to
the liver
- Solitary or multiple metastatic tumors in the liver
- Metastatic involvement of the liver no greater than 40% of estimated liver
volume NOTE: *Must be from the hepatic tumor designated for study injection
- Metastatic liver tumors must be bidimensionally measurable by CT scan or MRI
- At least 1 metastatic liver tumor measuring at least 2.0 cm must be visualized by
ultrasound (US) and accessible for US-guided percutaneous injection
- Extrahepatic metastases allowed
- No prior or current ascites
- Ineligible for hepatic resection
PATIENT CHARACTERISTICS:
Age
- Adult
Performance status
- Karnofsky 70-100%
Life expectancy
- At least 16 weeks
Hematopoietic
- Granulocyte count at least 1,500/mm^3
- Hemoglobin at least 9.0 g/dL
- Platelet count at least 100,000/mm^3
Hepatic
- No clinical evidence of other severe liver disease (e.g., portosystemic
encephalopathy)
- PT no greater than 14 seconds
- Bilirubin no greater than 2.0 times upper limit of normal (ULN)
- Transaminases no greater than 2.5 times ULN
Renal
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance at least 45 mL/min
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective nonhormonal contraception during and for at least
2 months after study participation
- HIV negative
- No active infection
- No other concurrent serious medical illness
- No other malignancy within the past 5 years except inactive nonmelanoma skin cancer,
carcinoma in situ of the cervix, or grade 1 papillary bladder cancer
- Oriented and rational
- Weight at least 30 kg
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
Endocrine therapy
- At least 2 months since prior corticosteroids
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- At least 2 months since prior systemic immunosupppressive drugs
- No concurrent immunosuppressive drugs
- No concurrent anticoagulant therapy with heparin or warfarin
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Max W. Sung, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mount Sinai School of Medicine
Authority:
Unspecified
Study ID:
CDR0000335463
NCT ID:
NCT00072098
Start Date:
September 2003
Completion Date:
Related Keywords:
- Colorectal Cancer
- Metastatic Cancer
- stage IV colon cancer
- stage IV rectal cancer
- liver metastases
- recurrent rectal cancer
- recurrent colon cancer
- Colorectal Neoplasms
- Neoplasm Metastasis
- Neoplasms
- Neoplasms, Second Primary
Name | Location |
|---|---|
| Mount Sinai Medical Center | New York, New York 10029 |
