Ovarian Cancer Treatment Research

Elesclomol and Paclitaxel Combo: A Missed Opportunity in Ovarian Cancer Treatment?

Elliot Brynn in Health & Wellness June 2025 • 4 min read.

"A recent study evaluates the effectiveness of combining elesclomol sodium with weekly paclitaxel for recurrent ovarian cancer. Discover the results and what they mean for future treatments."

Recurrent epithelial ovarian, primary peritoneal, and fallopian tube cancer (EOC) presents significant treatment challenges once platinum-based therapies become ineffective. After initial platinum treatment, typically single-agent chemotherapy, such as liposomal doxorubicin or topotecan, has been the standard when the platinum-free interval (PFI) is less than six months. For longer intervals, doublet chemotherapy is preferred.

For decades, the Gynecologic Oncology Group (GOG) has been at the forefront, seeking innovative solutions for recurrent ovarian cancer. Historically, only a few agents have demonstrated overall response rates (ORR) exceeding 20% in platinum-resistant cases. This reality underscores the urgent need for novel treatments to improve outcomes in recurrent EOC.

Elesclomol, known as STA-4783, is a novel molecule that enhances oxidative stress within cancer cells, potentially increasing their sensitivity to chemotherapy. Preclinical data suggested synergistic anti-tumor activity when combined with paclitaxel. Building on these findings, a phase 2 trial was initiated to explore the clinical benefits of elesclomol in combination with paclitaxel for recurrent ovarian cancer.

Elesclomol's Mechanism and Clinical Trial Results

Elesclomol functions by binding to copper ions in the bloodstream, allowing it to be efficiently taken up by cancer cells. Once inside, it promotes a redox reaction that increases reactive oxygen species (ROS) and oxidative stress. This mechanism is intended to disrupt mitochondrial metabolism, leading to cancer cell death while sparing normal cells.

A phase 2 study, NRG Oncology/Gynecologic Oncology Group trial, aimed to evaluate the effectiveness of elesclomol plus weekly paclitaxel in patients with platinum-resistant recurrent ovarian, tubal, or peritoneal cancer. The trial's primary goal was to estimate the anti-tumor activity of the combination through objective tumor responses.

Study Design: A prospective, multicenter phase 2 trial.
Participants: Patients with measurable disease, acceptable organ function, performance status ≤ 2, and one prior platinum-containing regimen.
Treatment: Elesclomol plus weekly paclitaxel.
Objectives: To estimate the objective response rate (ORR) and assess toxicity.

The study enrolled fifty-eight patients, with fifty-six being eligible and evaluable. The results indicated that the combination of elesclomol and paclitaxel, while well-tolerated, did not significantly improve the objective response rate. With 11 patients responding (19.6%), the study did not meet the predefined criteria for warranting further investigation. Progression-free survival was 3.6 months, and overall survival was 13.3 months.

Study Implications and Future Directions

Though preclinical models showed promise, this phase 2 trial found no added clinical benefit in terms of ORR when elesclomol was combined with weekly paclitaxel for platinum-resistant recurrent EOC. The study highlights the ongoing challenges in translating preclinical success to clinical efficacy, reminding us that factors such as drug resistance, immune surveillance, drug delivery, and the tumor microenvironment play critical roles.

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This article is based on research published under:

DOI-LINK: 10.1016/j.ygyno.2018.10.001, Alternate LINK

Title: A Phase Ii Evaluation Of Elesclomol Sodium And Weekly Paclitaxel In The Treatment Of Recurrent Or Persistent Platinum-Resistant Ovarian, Fallopian Tube Or Primary Peritoneal Cancer: An Nrg Oncology/Gynecologic Oncology Group Study

Subject: Obstetrics and Gynecology

Journal: Gynecologic Oncology

Publisher: Elsevier BV

Authors: Bradley J. Monk, James T. Kauderer, Katherine M. Moxley, Albert J. Bonebrake, Summer B. Dewdney, Angeles Alvarez Secord, Frederick R. Ueland, Carolyn M. Johnston, Carol Aghajanian

Published: 2018-12-01

Everything You Need To Know

What is Elesclomol, and how does it work?

Elesclomol, also known as STA-4783, is a novel molecule designed to enhance oxidative stress within cancer cells. It achieves this by binding to copper ions, which then allows it to be taken up by cancer cells. Once inside, it triggers a redox reaction, increasing reactive oxygen species (ROS) and oxidative stress. This mechanism is intended to disrupt the cancer cell's mitochondrial metabolism, leading to cell death. It was intended to make cancer cells more sensitive to chemotherapy, specifically paclitaxel.

Why was the combination of Elesclomol and Paclitaxel being studied, and why is this important?

The study investigated the combination of elesclomol and paclitaxel for recurrent ovarian, fallopian tube, or primary peritoneal cancer. This is significant because once platinum-based therapies fail, treatment options become limited. The trial specifically focused on cases where platinum-based therapies had become ineffective, representing a critical unmet need in cancer treatment. The goal was to find a more effective treatment for patients who have already become resistant to standard platinum-based chemotherapy.

What was the design of the clinical trial?

The phase 2 trial, conducted by NRG Oncology/Gynecologic Oncology Group, was designed as a prospective, multicenter study. It enrolled patients with measurable disease, acceptable organ function, a performance status of 2 or less, and who had undergone one prior platinum-containing regimen. The primary objective was to evaluate the objective response rate (ORR) and assess toxicity of the combination of elesclomol and weekly paclitaxel. Fifty-eight patients were enrolled, with fifty-six being eligible and evaluable.

What were the key findings of the study regarding Elesclomol and Paclitaxel?

The results of the phase 2 trial indicated that the combination of elesclomol and paclitaxel did not significantly improve the objective response rate (ORR). With only 19.6% of patients responding, the study did not meet the predefined criteria for further investigation. The progression-free survival was 3.6 months, and the overall survival was 13.3 months. This outcome suggests that, while preclinical data was promising, the combination did not provide a clinically significant benefit in this patient population in terms of tumor response.

What are the implications of the trial's results?

The implications of the study are that while the combination of elesclomol and paclitaxel was well-tolerated, it did not improve the objective response rate in platinum-resistant recurrent EOC. This underscores the challenges in translating success from preclinical models to clinical efficacy. The study highlights that factors such as drug resistance, immune surveillance, drug delivery, and the tumor microenvironment play critical roles, suggesting that further research is needed to understand why the combination was not effective in this setting and how to overcome resistance in future treatment strategies. It points to a missed opportunity and a need for alternative strategies.