ONC201 + Paclitaxel for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Ira Winer, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Ira Winer

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Other active cancers, Serious infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 28 days per cycle

62 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new drug, ONC201, combined with paclitaxel, a common chemotherapy medication, in treating ovarian, fallopian tube, or primary peritoneal cancer that resists standard platinum-based treatments. Researchers aim to determine if this combination can more effectively halt cancer growth compared to paclitaxel alone. The trial seeks participants with these cancer types whose disease has progressed despite previous treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot take other chemotherapy, immunotherapy, or hormonal anti-cancer therapies while on the study medications. Additionally, you must stop taking any drugs that are moderate to strong inhibitors or inducers of CYP3A4 at least one week before starting the trial.

Is there any evidence suggesting that ONC201 and paclitaxel are likely to be safe for humans?

Research has shown that ONC201 is generally safe. In studies, only about 9% of patients experienced serious side effects related to the treatment, with no reports of very severe side effects. The FDA granted accelerated approval for ONC201 to treat another type of cancer, indicating its safety.

Paclitaxel, a common chemotherapy drug, is also recognized for its safety. Many studies have demonstrated that paclitaxel has low toxicity. It is widely used to treat various cancers, with well-known and manageable side effects.

Both ONC201 and paclitaxel have undergone separate safety testing, and research suggests they are generally well-tolerated by patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Researchers are excited about the combination of ONC201 and Paclitaxel for ovarian cancer because it introduces a unique mechanism of action. ONC201 is a targeted therapy that activates stress responses in cancer cells, leading to their death, which is different from traditional chemotherapy approaches that kill all rapidly dividing cells. This combination could potentially enhance the efficacy of Paclitaxel, a standard chemotherapy drug, by specifically targeting cancer cells while minimizing harm to healthy ones. This innovative approach offers hope for improved outcomes in a condition that typically relies on more generalized treatments.

What evidence suggests that ONC201 and paclitaxel might be an effective treatment for ovarian cancer?

This trial will evaluate the combination of ONC201 and Paclitaxel for ovarian cancer. Studies have shown that ONC201 effectively kills cancer cells by disrupting crucial survival signals. In a previous trial, ONC201 achieved a 20% response rate, with 20% of patients experiencing tumor shrinkage or disappearance. Paclitaxel, a well-known chemotherapy drug, prevents cancer cells from dividing and spreading. It has been shown to help patients with ovarian cancer live longer without disease progression. Combining ONC201 with Paclitaxel in this trial may enhance treatment effectiveness for hard-to-treat ovarian cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Ira S. Winer

Principal Investigator

Barbara Ann Karmanos Institute

Are You a Good Fit for This Trial?

This trial is for women with certain types of ovarian, fallopian tube, or primary peritoneal cancer that's resistant to platinum-based chemotherapy. Participants should have at least one measurable lesion and be in good physical condition (ECOG score 0-1). They must not be pregnant or breastfeeding, agree to use contraception, and have adequate organ function. Those with more than four prior treatments in the resistant setting or a total of seven overall are excluded.

Inclusion Criteria

I am not pregnant, not breastfeeding, and if able to bear children, I agree to use contraception during the study.

You have at least one specific spot that can be measured according to a certain set of rules.

My cancer got worse within 6 months after finishing a platinum-based treatment.

Exclusion Criteria

I haven't had major surgery in the last 3 weeks or minor surgery in the last week.

Pregnant or lactating

I have ovarian cancer and no other active cancers requiring treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ONC201 orally on days 1, 8, and 15, and paclitaxel intravenously over 1 hour on days 2, 9, and 16. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

1 year

What Are the Treatments Tested in This Trial?

Interventions

• ONC201
• Paclitaxel

Trial Overview The trial is testing ONC201 combined with weekly paclitaxel against these cancers. ONC201 targets specific receptors on cancer cells while paclitaxel stops their growth by various means. The study aims to see if this combination works better than paclitaxel alone for patients who haven't responded well to previous platinum-based therapies.

How Is the Trial Designed?

Group I: Treatment - ONC201 & Paclitaxel Experimental Treatment 3 Interventions

Patients receive ONC201 PO on days 1, 8, 15, and 22 and paclitaxel IV over 1 hour on days 2, 9, and 16. Cycles repeat every 28 days in the absence disease progression or unacceptable toxicity. If paclitaxel must be stopped for any reason, patients may continue on ONC201 alone.

Who Is Running the Clinical Trial?

Ira Winer

Lead Sponsor

Trials

2

Recruited

130+

Published Research Related to This Trial

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

Paclitaxel and docetaxel, two taxanes used in treating ovarian cancer, have shown clinical activity, with response rates of 20-48% for paclitaxel and 33-35% for docetaxel in previously treated patients, indicating their efficacy even in platinum-resistant tumors.

Premedication with dexamethasone, diphenhydramine, and cimetidine can significantly reduce the risk of severe allergic reactions to taxanes to less than 3%, highlighting a safety measure for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Options for primary chemotherapy of epithelial ovarian cancer: taxanes. Trimble, EL., Arbuck, SG., McGuire, WP.[2018]

In a study of 70 patients with platinum-resistant recurrent ovarian cancer, the combination of apatinib and paclitaxel significantly improved disease control rates (84.4% vs. 60.5%) and prolonged progression-free survival (5.0 months vs. 3.8 months) compared to paclitaxel alone.

The combination treatment also resulted in a longer overall survival (21.1 months vs. 14.8 months) without increasing the incidence of adverse events, indicating that apatinib plus paclitaxel is both effective and safe for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apatinib plus paclitaxel versus paclitaxel monotherapy for platinum-resistant recurrent ovarian cancer treatment: A retrospective cohort study. Geng, A., Yang, H., Wang, Z., et al.[2022]

A platinum/taxane combination is identified as the optimal treatment backbone for chemonaive ovarian cancer based on trials from the Gynecologic Oncology Group over the past 15 years.

Adding a third drug to this combination is unlikely to significantly improve outcomes; however, using sequential doublets of drugs like cisplatin with gemcitabine or topotecan with doxil or etoposide may enhance treatment efficacy due to their complementary mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Gynecologic Oncology Group experience in ovarian cancer. McGuire, WP., Brady, MF., Ozols, RF.[2022]

The combination of doxorubicin, carboplatin, and weekly paclitaxel in treating advanced epithelial ovarian cancer (EOC) shows activity, with 4 out of 12 patients achieving partial remission and 3 having stable disease.

The main toxicity observed was myelosuppression, particularly grade 4 neutropenia, but the weekly administration of paclitaxel allowed for maintaining an effective dose intensity (approximately 65 mg/m²/week) while managing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma. Hess, V., Verrill, MW., Bomphray, CC., et al.[2020]

Paclitaxel has been established as an effective treatment for newly diagnosed ovarian cancer patients, leading to its incorporation into primary chemotherapy regimens, particularly in combination with cisplatin as the new standard in the U.S.

Ongoing clinical trials are exploring various strategies to optimize paclitaxel-based chemotherapy, including comparisons of different platinum-based drugs and infusion schedules, as well as evaluating high-dose therapies with stem cell support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of advanced ovarian cancer: current status and future directions. Ozols, RF., Vermorken, JB.[2015]

Paclitaxel (Taxol) is an effective chemotherapy agent for treating ovarian cancer and metastatic breast cancer, particularly in patients who have not responded to platinum-based treatments.

Nurses must be aware of the potential side effects of Paclitaxel, such as hypersensitivity reactions and peripheral neuropathy, and follow specific administration guidelines to avoid complications related to its interaction with PVC intravenous-giving sets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol)--a guide to administration. Preston, NJ.[2019]

Paclitaxel (TAXOL) has shown response rates of 20% to 35% in patients with refractory ovarian cancer, particularly in those with platinum-resistant disease, making it a promising treatment option.

Toxicity associated with paclitaxel is primarily hematologic and neurologic, with studies indicating that hematologic toxicity is schedule-dependent while neurologic toxicity is dose-dependent, suggesting careful management of dosing and scheduling in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol) therapy in ovarian carcinoma. Caldas, C., McGuire, WP.[2015]

Recent advances in targeted treatments for recurrent ovarian cancer (OC) show promise in improving response rates and extending progression-free survival, addressing the limitations of traditional chemotherapy.

The FDA has established an 'accelerated approval' pathway for new therapies to meet the urgent need for effective treatments in advanced OC, as current options often fail to provide clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bringing new medicines to women with epithelial ovarian cancer: what is the unmet medical need? Herzog, TJ., Monk, BJ.[2022]

A Phase I study involving 23 patients with advanced ovarian cancer tested a new chemotherapy regimen combining intravenous paclitaxel and intraperitoneal cisplatin, followed by intraperitoneal paclitaxel, showing that 95% of participants completed all six planned treatment cycles.

While some patients experienced dose-limiting toxicities, including infections and abdominal pain, the overall regimen was deemed feasible, suggesting it could be a safer alternative to traditional intraperitoneal chemotherapy methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I feasibility study of intraperitoneal cisplatin and intravenous paclitaxel followed by intraperitoneal paclitaxel in untreated ovarian, fallopian tube, and primary peritoneal carcinoma: a gynecologic oncology group study. Dizon, DS., Sill, MW., Gould, N., et al.[2021]

In a study involving 238 patients with platinum-resistant ovarian cancer, those treated with chemotherapy had a longer median progression-free survival (PFS) of 12.7 weeks compared to 8.3 weeks for those on tamoxifen, indicating chemotherapy may be more effective in delaying disease progression.

However, patients receiving chemotherapy reported poorer health-related quality of life (HRQoL) and experienced more social functioning issues, suggesting that while chemotherapy may extend survival, it comes with increased toxicity and impacts on quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist). Lindemann, K., Gibbs, E., Åvall-Lundqvist, E., et al.[2018]

Inhibiting Src family and Abl kinases using siRNAs or dasatinib significantly enhances the sensitivity of ovarian cancer cells to paclitaxel, as demonstrated in both cell cultures and HEY xenograft models.

The mechanism involves the induction of p27(Kip1), which promotes apoptosis by suppressing Bcl-2 and Cdk1 expression, leading to increased effectiveness of paclitaxel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. Le, XF., Mao, W., He, G., et al.[2021]

Intraperitoneal paclitaxel (PTX) was well tolerated and showed promising anti-cancer activity in a small study of 13 patients with advanced gynecologic cancer undergoing neoadjuvant chemotherapy.

After treatment, 10 out of 11 patients were able to undergo optimal interval debulking surgery, indicating that PTX (ip) may effectively prepare patients for surgery without the need for extensive resections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Neoadjuvant chemotherapy with intraperitoneal paclitaxel for advanced gynecologic cancer]. Inatomi, S., Shimamoto, K., Fujimoto, H., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12025107/

ONC201 (Dordaviprone) Induces Integrated Stress ... ONC201 exerted significant cytotoxicity and inhibited the clonogenic potential of cervical cancer cells. It induced integrated stress response along with S/G2-M ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10541180/

ONC201/TIC10 enhances durability of mTOR inhibitor ... A combination of everolimus and ONC201/TIC10 inhibited growth of resistant cancer cells that had been grown in a three-dimensional arrangement to mimic human ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.10017

Efficacy and safety of dordaviprone (ONC201) in ... 12-month PFS rate was not reached; 12-month OS rate was 27.3% (6.5, 53.9). One patient experienced a grade ≥3 TR-TEAE (9.1%); no TR-SAEs, ...

4. onclive.com onclive.com/view/fda-grants-priority-review-to-dordaviprone-in-recurrent-h3k27m-diffuse-glioma

FDA Grants Priority Review to Dordaviprone in Recurrent ... The drug demonstrated a 20% objective response rate and 40% disease control rate in clinical trials.

5. karmanos.org karmanos.org/karmanos/blog/2269

Karmanos Researcher Co-discovered Compound, Led to ... Preclinical and clinical trials revealed that ONC201 worked in multiple ways: it shut down survival signals inside cancer cells (ERK and AKT), ...

6. onclive.com onclive.com/view/dordaviprone-in-patients-with-recurrent-h3k27m-mutant-dmg

Dordaviprone in Patients with Recurrent H3K27M-Mutant ... Experts discuss dordaviprone as a promising new treatment for diffuse midline gliomas with H3K27M mutations, highlighting its dual mechanism ...

7. cancernetwork.com cancernetwork.com/view/newly-approved-agent-for-diffuse-midline-glioma-shows-tolerable-ae-profile

Newly Approved Agent for Diffuse Midline Glioma Shows ... In August 2025, the FDA granted accelerated approval to the protease activator dordaviprone as a. Dordaviprone was recommended at a dose of 625 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8970020/

Anti-Tumor and Anti-Invasive Effects of ONC201 on ... ONC201 significantly suppressed tumor growth, and decreased serum VEGF production in obese and lean mice, leading to a decrease in tumoral expression of Ki-67, ...