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

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects of ONC201 and paclitaxel and how well they work in treating patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent), or that does not respond to treatment (refractory). ONC201 is the first in its class of drugs that antagonize some specific cell receptors on cancer cells, leading to their destruction. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ONC201 and paclitaxel may work better in treating patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer compared to paclitaxel alone.

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.

What data supports the effectiveness of the drug ONC201 + Paclitaxel for ovarian cancer?

Paclitaxel, a component of the treatment, has been shown to be effective in treating ovarian cancer, especially when combined with other drugs like cisplatin. It is part of the standard chemotherapy regimen for newly diagnosed ovarian cancer patients. ^{1 2 3 4 5}

What safety data exists for ONC201 and Paclitaxel in humans?

Paclitaxel, used in treating ovarian cancer, can cause side effects like hypersensitivity (allergic reactions), low white blood cell count, nerve damage, hair loss, and muscle or joint pain. Premedication can reduce severe allergic reactions to less than 3%. The safety of ONC201 in humans is not detailed in the provided research. ^{6 7 8 9 10}

What makes the drug ONC201 + Paclitaxel unique for ovarian cancer?

The combination of ONC201 and Paclitaxel is unique because it explores a novel approach by combining a new agent, ONC201, with Paclitaxel, which is already a standard treatment for ovarian cancer. This combination aims to enhance the effectiveness of Paclitaxel, especially in cases where the cancer is resistant to platinum-based treatments. ^{2 5 11 12 13}

Research Team

Ira S. Winer

Principal Investigator

Barbara Ann Karmanos Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 (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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Apatinib plus paclitaxel versus paclitaxel monotherapy for platinum-resistant recurrent ovarian cancer treatment: A retrospective cohort study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy of advanced ovarian cancer: current status and future directions. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist). [2018]

4. England pubmed.ncbi.nlm.nih.gov

The Gynecologic Oncology Group experience in ovarian cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Bringing new medicines to women with epithelial ovarian cancer: what is the unmet medical need? [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

[Neoadjuvant chemotherapy with intraperitoneal paclitaxel for advanced gynecologic cancer]. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Options for primary chemotherapy of epithelial ovarian cancer: taxanes. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma. [2020]

9. England pubmed.ncbi.nlm.nih.gov

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

10. United States 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. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol) therapy in ovarian carcinoma. [2015]

13. United States pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. [2015]