Relacorilant + Nab-paclitaxel + Bevacizumab for Ovarian Cancer

Recruiting at 3 trial locations

Overseen By Corcept Therapeutics

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Corcept Therapeutics

Must not be taking: Corticosteroids, Mifepristone

Disqualifiers: Hypertension, Peripheral neuropathy, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: Up to 18 months

90 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain treatments like corticosteroids, hormonal anticancer therapies, or anticoagulants close to the start of the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Relacorilant, Nab-paclitaxel, and Bevacizumab for ovarian cancer?

Research shows that combining paclitaxel and bevacizumab can help patients with recurrent ovarian cancer live longer without the disease getting worse. Bevacizumab, when used with other chemotherapy drugs, has also been shown to improve outcomes in ovarian cancer. ^{1 2 3 4 5}

Is the combination of Relacorilant, Nab-paclitaxel, and Bevacizumab safe for humans?

Bevacizumab has been used safely in various cancers, including ovarian cancer, but it can cause high blood pressure and, rarely, serious issues like gastrointestinal perforation and kidney or brain problems. Nab-paclitaxel is generally safe and reduces the risk of allergic reactions compared to other similar drugs, with common side effects including fatigue, liver enzyme changes, low white blood cell count, low platelet count, and anemia. There is no specific safety data available for Relacorilant in this combination. ^{3 6 7 8 9}

How is the drug combination of Relacorilant, Nab-paclitaxel, and Bevacizumab unique for treating ovarian cancer?

This drug combination is unique because it includes Relacorilant, which is not commonly used in standard ovarian cancer treatments. Bevacizumab is known for targeting blood vessel growth in tumors, and Nab-paclitaxel is a form of chemotherapy, but the addition of Relacorilant may offer a novel approach by potentially enhancing the effectiveness of these drugs. ^{1 3 5 10 11}

What is the purpose of this trial?

This is a Phase 2, single-arm, open-label study to evaluate efficacy and safety of intermittent dosing of relacorilant in combination with nab-paclitaxel and bevacizumab in patients with ovarian cancer.

Research Team

Bhagyashree Yadav

Principal Investigator

Corcept Therapeutics

Eligibility Criteria

This trial is for adults with advanced ovarian, primary peritoneal, or fallopian-tube cancer who've had up to three prior treatments. They must be able to take oral meds, have a good performance status (able to carry out daily activities), and have at least one measurable tumor. Those resistant to platinum-based therapy after less than 6 months can join.

Inclusion Criteria

My doctor expects me to live 3 months or more.

I have at least one tumor that can be measured.

I have been diagnosed with a specific type of ovarian, peritoneal, or fallopian tube cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive relacorilant in combination with nab-paclitaxel and bevacizumab. Relacorilant is administered orally for 3 consecutive days around nab-paclitaxel infusion, which is given on Days 1, 8, and 15 of each 28-day cycle. Bevacizumab is administered on Days 1 and 15 of each cycle.

Up to 18 months

Visits on Days 1, 8, and 15 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Bevacizumab
• Nab-paclitaxel
• Relacorilant

Trial Overview The study tests relacorilant combined with nab-paclitaxel and bevacizumab in patients with certain types of ovarian cancer. It's an open-label Phase 2 trial where all participants receive the same treatment regimen to assess its effectiveness and safety.

Participant Groups

Group I: Relacorilant in Combination with Nab-paclitaxel and Bevacizumab Experimental Treatment 3 Interventions

The patient will receive relacorilant 150 mg, administered orally under fed conditions, once daily for 3 consecutive days on the day before, the day of, and the day after nab-paclitaxel infusion. Nab-paclitaxel (80 mg/m\^2) will be administered by IV infusion on Days 1, 8, and 15 of each 28-day cycle. Bevacizumab (10 mg/kg) will be administered by IV infusion on Days 1 and 15 of each 28-day cycle.

Who Is Running the Clinical Trial?

Corcept Therapeutics

Lead Sponsor

Trials

72

Recruited

7,700+

Dr. Joseph K. Belanoff

Corcept Therapeutics

Chief Executive Officer since 2014

MD from Stanford University

Dr. William Guyer

Corcept Therapeutics

Chief Medical Officer since 2021

PharmD

Findings from Research

Bevacizumab has been shown to be effective in managing epithelial ovarian cancer, particularly when combined with cytotoxic chemotherapy, as indicated by phase III trial data that demonstrate improved progression-free survival.

There is a compelling argument for using bevacizumab as a single agent in patients with platinum-resistant ovarian cancer, suggesting a more rational and potentially cost-effective approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. Markman, M.[2020]

In a phase III trial involving 484 patients with platinum-sensitive recurrent ovarian cancer, the combination of bevacizumab (BV) with gemcitabine and carboplatin (GC) significantly improved progression-free survival (PFS) compared to GC alone, with a median PFS of 12.4 months versus 8.4 months.

The addition of BV also led to a higher objective response rate (78.5% vs. 57.4%) and longer duration of response (10.4 months vs. 7.4 months), although it was associated with increased rates of grade 3 or higher hypertension and proteinuria, indicating a need for monitoring these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. Aghajanian, C., Blank, SV., Goff, BA., et al.[2022]

In a study of 51 patients with recurrent epithelial ovarian cancer, the combination of weekly paclitaxel and biweekly bevacizumab showed a high overall response rate of 60%, with a median progression-free survival of 7 months and median overall survival of 12 months.

The treatment was found to have an acceptable toxicity profile, with the most severe side effects being fatigue (16%), hematologic issues (9%), and neurotoxicity (7%), indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained progression-free survival with weekly paclitaxel and bevacizumab in recurrent ovarian cancer. Hurt, JD., Richardson, DL., Seamon, LG., et al.[2015]

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor-A, has shown response rates of 16-21% as a single-agent treatment for recurrent ovarian cancer, indicating its efficacy in this context.

In combination with standard chemotherapy for advanced ovarian cancer, bevacizumab significantly improves progression-free survival, although it does not enhance overall survival; the main safety concern is hypertension, with rare but serious risks including gastrointestinal perforation and toxicity to the kidneys and central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and ovarian cancer. Garcia, A., Singh, H.[2021]

In a study of 299 patients with advanced ovarian cancer, combining bevacizumab with carboplatin/paclitaxel resulted in a median progression-free survival of 15.4 months, indicating its efficacy as a front-line treatment.

The treatment was generally safe, with 54% of patients experiencing grade 3/4 adverse events, primarily hypertension and neutropenia, and a 1-year overall survival rate of 94%, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study. Hall, M., Bertelli, G., Li, L., et al.[2020]

In a study of 164 patients with recurrent ovarian cancer, the combination of bevacizumab (BEV) with paclitaxel and carboplatin significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to the control group receiving only paclitaxel and carboplatin.

The experimental group experienced fewer adverse reactions, such as allergies and gastrointestinal issues, and showed a significant improvement in quality of life after treatment, indicating that BEV combined with paclitaxel is both effective and safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of bevacizumab combined with paclitaxel and carboplatin on recurrent ovarian cancer. Cong, J., Liu, R., Hou, J., et al.[2020]

In a phase 3 trial involving 682 patients with recurrent ovarian cancer, the combination of carboplatin-pegylated liposomal doxorubicin and bevacizumab showed a median progression-free survival of 13.3 months, significantly longer than the 11.6 months observed with the standard carboplatin-gemcitabine-bevacizumab regimen (p=0.012).

The safety profile was comparable between the two treatment groups, with hypertension and neutropenia being the most common severe adverse events; however, treatment-related deaths were rare, occurring in less than 1% of patients in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Pfisterer, J., Shannon, CM., Baumann, K., et al.[2022]

Bevacizumab, a monoclonal antibody that targets VEGF, has shown anticancer activity in ovarian cancer, both as a single agent and in combination with chemotherapy, leading to its FDA approval for several cancers.

While bevacizumab can be effective, there is a significant risk of gastrointestinal perforation, especially in patients who have been heavily pretreated, which is an important consideration for patients and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and its use in epithelial ovarian cancer. Matulonis, UA.[2019]

References

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

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. [2020]

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

Phase II trial of bevacizumab with dose-dense paclitaxel as first-line treatment in patients with advanced ovarian cancer. [2018]

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

OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. [2022]

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

Sustained progression-free survival with weekly paclitaxel and bevacizumab in recurrent ovarian cancer. [2015]

5. France pubmed.ncbi.nlm.nih.gov

Phase I Study of Rucaparib in Combination with Bevacizumab in Ovarian Cancer Patients: Maximum Tolerated Dose and Pharmacokinetic Profile. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Bevacizumab and ovarian cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study. [2020]

8. Italy pubmed.ncbi.nlm.nih.gov

First-line carboplatin/nab-paclitaxel in advanced ovarian cancer patients, after hypersensitivity reaction to solvent-based taxanes: a single-institution experience. [2020]

9. Cyprus pubmed.ncbi.nlm.nih.gov

Therapeutic effect of bevacizumab combined with paclitaxel and carboplatin on recurrent ovarian cancer. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Bevacizumab and its use in epithelial ovarian cancer. [2019]