Clinical trial NCT00107861: Interferon-Beta Gene Transfer (Ad.hIFN-β) as Treatment for Refractory Colorectal Carcinoma With Liver Metastases
Official title: A Phase I/II Study of Interferon-Beta Gene Transfer (Ad.hIFN-β) in the Treatment of Refractory Colorectal Carcinoma With Liver Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Carcinoma
Metastases
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2005-04-12
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will be conducted in subjects with refractory colorectal carcinoma with unresectable liver metastases. The purposes of the study are:

* to evaluate the safety and any harmful effects of an intravenous injection of Ad.hIFN-β;
* help determine whether the virus carrying the interferon-beta gene will enter the bloodstream and liver tumor cells and cause the cancer cells to die.

Detailed description: This trial is a clinical research study of Ad.hIFN-β, an investigational, replication-defective, recombinant adenovirus containing the human interferon beta gene, for people that have refractory colorectal carcinoma with liver metastases. Scientists have been exploring a variety of approaches to develop medications to treat patients with refractory colorectal carcinoma with liver metastases; a disease for which current treatment provides only limited relief, so there is a need for new medications.

Eligibility criteria: Inclusion Criteria:

* Subjects with histologically confirmed hepatic metastases from primary colorectal carcinoma.
* Not amenable to complete surgical resection for attempted cure as determined by the Principal Investigator (PI).
* Tumor progression after prior therapy for colorectal carcinoma, including fluoropyrimidine (5 FU or capecitabine), irinotecan, oxaliplatin, or cetuximab.
* One or more metastatic hepatic tumors that is measurable on CT scan. In addition, subjects may have nonhepatic metastatic tumors.
* ECOG performance status of ≤ 1.
* Age ≥ 18 years.
* Signed, written IRB-approved informed consent.
* Men and women of reproductive potential must be willing to follow accepted birth control methods during treatment and for 3 months after completion of treatment.
* Acceptable liver function:

  * Bilirubin ≤ 1.5 x upper limit of normal;
  * AST, ALT ≤ 2.0 x upper limit of normal;
  * Albumin ≤ 3.0 g/dL.
* Acceptable hematologic status:

  * Granulocyte ≥ 1000 cells/mm3;
  * Platelet count ≥ 150,000 plts/mm3;
  * Hemoglobin \> 9 g/dL.
* Acceptable coagulation status: INR within normal limits.
* Acceptable kidney function: Serum creatinine within normal limits.

Exclusion Criteria:

* New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months prior to Day 1, unstable arrhythmia, or evidence of ischemia on ECG within 14 days prior to Day 1.
* Seizure disorders requiring anticonvulsant therapy.
* Severe chronic obstructive pulmonary disease with hypoxemia.
* Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1.
* Active uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
* Pregnant or nursing women.
* Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 1 month prior to study entry.
* Unwillingness or inability to comply with procedures required in this protocol.
* Known infection with HIV, hepatitis B, or hepatitis C.
* Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
* Clinically significant bleeding event within the last 3 months, unrelated to trauma.
* More than 50% of liver replaced by tumor (estimated by the PI from CT scan within 14 days of Day 1).
* Previous treatment with Ad.hIFN-β.
* Any prior treatment with a gene delivery vector or an adenovirus therapeutic agent.

Primary outcomes:
measure: - Evaluate the safety of a single IV administration of Ad.hIFN-β.
Secondary outcomes:
measure: Evaluate the MTD or maximum feasible dose (MFD) of Ad.hIFN-β.
measure: Evaluate IFN-β and Ad.hIFN-β vector serum concentrations.
measure: Evaluate immunogenicity of Ad.hIFN-β by measuring human anti adenovirus and human anti-IFN-β antibody formation.
measure: Explore preliminary clinical activity.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
Study officials:
References: