Clinical trial NCT00093548: Vaccine Therapy in Treating Patients With Stage II, Stage IIIA, Stage IIIB, or Stage IVA Liver Cancer
Official title: A Phase I/II Trial Testing Immunization With AFP + GM-CSF Plasmid Prime And AFP Adenoviral Vector Boost In Patients With Hepatocellular Carcinoma (AFP Prime-Boost Protocol)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Liver Cancer
Keywords: adult primary hepatocellular carcinoma
advanced adult primary liver cancer
localized resectable adult primary liver cancer
localized unresectable adult primary liver cancer
Lead sponsor: Jonsson Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-10-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines made from DNA and a gene-modified virus may make the body build an immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of liver cancer.

PURPOSE: This phase I/II trial is studying the side effects and best dose of vaccine therapy and to see how well it works in treating patients with stage II, stage IIIA, stage IIIB, or stage IVA liver cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the dose-limiting toxicity and maximum tolerated dose of adjuvant vaccination comprising alpha fetoprotein (AFP) plasmid DNA and sargramostim (GM-CSF) plasmid DNA followed by AFP adenoviral vector boost in patients with HLA-A\*0201-expressing stage II-IVA hepatocellular carcinoma.

Secondary

* Determine the optimal biological dose of this regimen, as defined by the generation of AFP-specific immunity, in these patients.
* Determine disease-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of alpha fetoprotein (AFP) adenoviral vector boost.

Patients receive vaccination comprising AFP plasmid DNA and sargramostim (GM-CSF) plasmid DNA intramuscularly (IM) on days 1, 30, and 60 in the absence of unacceptable toxicity. Patients then receive boost immunization comprising AFP adenoviral vector IM and intradermally on day 90.

Cohorts of 3-6 patients receive escalating doses of AFP adenoviral vector boost 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 monthly for 3 months and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 3-25 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of hepatocellular carcinoma

  * Stage II-IVA disease

    * No active disease after local or regional therapy (e.g., surgical resection, radiofrequency ablation, cryoablation, or ethanol injection)
* Serum alpha fetoprotein \> upper limit of normal
* HLA-A\*0201 positive by DNA subtyping

PATIENT CHARACTERISTICS:

Age

* Over 18

Performance status

* Karnofsky 70-100%

Life expectancy

* Not specified

Hematopoietic

* Hemoglobin \> 9.0 g/dL (transfusion independent)
* Platelet count \> 50,000/mm\^3
* Absolute neutrophil count \> 1,000/mm\^3

Hepatic

* Child Pugh class A or B liver function
* Hepatitis B or C viral infection allowed

Renal

* Not specified

Cardiovascular

* No New York Heart Association class III or IV cardiac insufficiency
* No coronary artery disease

Immunologic

* HIV negative
* No other acute viral, bacterial, or fungal infection requiring therapy
* No allergy to study agents
* No history of opportunistic infection
* No high serum titer of neutralizing anti-adenoviral antibodies
* No congenital or acquired condition resulting in an inability to generate an immune response

Other

* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective double-method (including a barrier method) contraception
* No other condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* At least 30 days since prior chemotherapy
* No concurrent cytotoxic chemotherapy

Endocrine therapy

* At least 30 days since prior steroid therapy
* No concurrent steroid therapy, including corticosteroids

Radiotherapy

* Not specified

Surgery

* See Disease Characteristics
* No prior organ allograft

Other

* At least 2 weeks since prior therapy for acute infection
* No concurrent immunosuppressive therapy
* No concurrent cyclosporine

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Antoni Ribas, MD
role: STUDY_CHAIR
References:
citation: Butterfield LH, Economou JS, Gamblin TC, Geller DA. Alpha fetoprotein DNA prime and adenovirus boost immunization of two hepatocellular cancer patients. J Transl Med. 2014 Apr 5;12:86. doi: 10.1186/1479-5876-12-86.