Rexin-G is a tumor-targeted gene medicine that is designed to seek out and destroy both
primary tumors and metastatic cancers without the side effects of standard chemotherapy. The
objectives of the study are: (1) to evaluate the clinical effectiveness of intravenous
injections of Rexin-G, a tumor-targeted gene vector, in controlling tumor growth and
prolonging life, and (2) to evaluate its over-all safety.
The adaptive trial design of this advanced Phase II study incorporates (i) a dosing schedule
based on the patient's estimated tumor burden and not on standard dosing per kilogram body
weight or body surface area, and (2) a tumor response evaluation process that is unique to
the manner in which osteosarcoma responds favorably to therapy, i.e., with necrosis and
increasing calcification in metastatic tumors and decreased glucose utilization using PET-CT
Twenty to thirty patients will receive Rexin-G at either Dose Level 1 or 2. Patients will be
assigned a dose level based on the estimated tumor burden as measured by PET-CT imaging
studies. Estimated tumor burden is measured by multiplying the sum of the longest diameters
of target lesions in cm by 10e9 cancer cells. If the tumor burden is less than 10 billion
cells, the patient will be assigned to Dose Level 1, if the tumor burden is greater than 10
billion cells, the patient will be assigned to Dose Level 2.
*Treatment Cycle Dose Level Vector Dose/Day Max.Volume/Dose
Two times a week 1 1.0 x 10e11 cfu 200 ml
Three times a week 2 1.0 x 10e11 cfu 200 ml
* Each treatment cycle will be six weeks (four weeks of treatment and two weeks of rest).
Patients who have resolution of toxicity to < grade I may have repeat cycles. After one or
more treatment cycles, the principal investigator may recommend surgical debulking or
complete surgical removal. If residual disease is present either by histopathological
examination or by PET-CT scan, repeat treatment cycles may be given 3-4 weeks after surgery,
if the surgical incision has healed, and if the patient has < grade I toxicity.
1. Patient with recurrent or metastatic osteosarcoma who is considered refractory to
2. Histologically or cytologically confirmed osteosarcoma that is measurable.
3. Adequate hepatic function: Total bilirubin < 2.0 mg/dL (upper limit included);
AST/ALT < 2x institutional norm; alkaline phosphatase < 2.5x upper limit of
institutional norm unless the patient has extensive bone metastases. Patients with
elevated alkaline phosphatase due to extensive liver disease will be excluded from
study; albumin > 3.0 mg/dL. There must be no substantial ascites. PT and PTT must be
within normal limits.
4. Performance status must be < 1 (ECOG 0-1) with a life expectancy of at least 3
5. Hemoglobin > 9 gms%
6. Absolute granulocyte count > 1000/uL, and platelet count > 100,000/uL.
7. Serum creatinine of less than 1.5 mg%.
8. There must be no plans for the patient to receive further cancer therapy from the
date of enrollment until the completion of the 6-week follow-up visit.
9. Accessibility of peripheral or central IV line
10. Age > 10 years
11. Patients will be off chemotherapy for a minimum of 4 weeks prior to initiation of
therapy and should have recovered to Grade 1 or less toxicity.
12. The ability to understand and the willingness to sign a written informed consent
1. Prior malignancy, except for non-melanoma skin cancer, stage 1 breast cancer, CIS of
cervix from which the patient has been disease-free for 5 years.
2. Woman who are pregnant or nursing
3. Fertile patients unless they agree to use barrier contraception (condoms and
spermicide jelly) during the vector infusion period and for six weeks after infusion.
Male patients must agree to use barrier contraception.
4. Patients who are transfusion dependent (more than one transfusion per month)
5. Patients with medical, psychiatric, or social conditions that would compromise
successful adherence to this protocol.
6. Patient who do not meet the inclusion criteria.