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Updated: Sep 26, 2026
A Coregistered Ultrasound and Photoacoustic Imaging Protocol for the Transvaginal Imaging of Ovarian Lesions
Published on: March 3, 2023
Phase II study of CGP 69846A (ISIS 5132) in recurrent epithelial ovarian cancer: an NCIC clinical trials group study
1Princess Margaret Hospital, Toronto, M5G 2M9 Ontario, Canada. amit.oza@uhn.on.ca
Objective:
ISIS 5132 is a 20-base phosphorothioate DNA oligonucleotide against human c-raf kinase, a downstream effector of ras oncogene function. C-raf kinase is a molecule in the MAP kinase signaling cascade which is essential for cellular proliferation, the overexpression of which leads to malignant expression. Activity of this compound was documented in a woman with ovarian cancer in a Phase I study.
Methods:
We evaluated ISIS 5132 at a dose of 4 mg/kg/day by continuous venous infusion, administered for 21 days q 4 weeks in 22 patients with recurrent ovarian cancer in a standard two-stage Phase II design. Three patients were ineligible; 19 patients are evaluable for toxicity and 16 for response. All patients had previously received systemic therapy for ovarian cancer (6 had one and 13 had two prior regimens). Patients were treated with a median of two cycles and 79% of the patients received >90% planned dose intensity.
Results:
ISIS 5132 was well tolerated with no episodes of Grade 3 or 4 hematologic or biochemical (creatinine, AST, bilirubin) toxicity. There were six episodes of grade 3 nonhematologic toxicity in 4 patients thought to be treatment related (lethargy 2; anorexia 1; abdominal pain 2; shortness of breath 1). No responses were seen in the 16 patients who are evaluable for response; 4 had stable disease for a median of 3.8 months and 12 patients had documented progressive disease.
Conclusion:
ISIS 5132 at 4 mg/kg/day as a single agent did not show activity in recurrent ovarian cancer.
Insights
ISIS 5132, a c-raf kinase inhibitor, showed no activity in recurrent ovarian cancer patients. The investigational drug was well-tolerated but did not demonstrate efficacy in this Phase II trial.
Area of Science:
- Molecular oncology
- Cancer therapeutics
- Signal transduction inhibitors
Background:
- C-raf kinase is a key mediator in the MAP kinase signaling cascade, crucial for cell proliferation.
- Overexpression of c-raf kinase is linked to malignant progression in various cancers.
- ISIS 5132 is a novel DNA oligonucleotide designed to inhibit human c-raf kinase activity.
Purpose of the Study:
- To evaluate the clinical activity of ISIS 5132 in patients with recurrent ovarian cancer.
- To assess the safety and tolerability of ISIS 5132 as a single agent in this patient population.
Main Methods:
- A Phase II, two-stage study design was employed.
- Twenty-two patients with recurrent ovarian cancer received ISIS 5132 at 4 mg/kg/day via continuous venous infusion for 21 days every 4 weeks.
- Patients had received prior systemic therapy; 19 were evaluable for toxicity and 16 for response.
Main Results:
- ISIS 5132 was generally well-tolerated, with no Grade 3 or 4 hematologic or biochemical toxicities.
- Grade 3 nonhematologic toxicities included lethargy, anorexia, abdominal pain, and shortness of breath.
- No objective responses were observed; 4 patients achieved stable disease for a median of 3.8 months, while 12 had progressive disease.
Conclusions:
- ISIS 5132, administered as a single agent at 4 mg/kg/day, did not demonstrate significant clinical activity in recurrent ovarian cancer.
- Further investigation of ISIS 5132 in ovarian cancer may require combination strategies or different dosing regimens.