Lurbinectedin + Paclitaxel + Bevacizumab for Ovarian Cancer

Overseen By Shannon Westin, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-VEGF, Anticancer drugs

Disqualifiers: Pregnancy, Cardiovascular issues, Infections, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

34 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if adding lurbinectedin to the combination of paclitaxel and bevacizumab can help to control advanced cancer.

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 have received anti-cancer treatment within 2 weeks before starting the trial, and there must be at least 10 days between stopping any prior treatment and starting the study treatment.

What data supports the effectiveness of the drug combination Lurbinectedin, Paclitaxel, and Bevacizumab for ovarian cancer?

Research shows that combining bevacizumab with paclitaxel and other drugs can improve progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in ovarian cancer patients. Bevacizumab has been effective in managing ovarian cancer, especially when used with other chemotherapy drugs. ^{1 2 3 4 5}

Is the combination of Lurbinectedin, Paclitaxel, and Bevacizumab safe for humans?

Research shows that the combination of Bevacizumab and Paclitaxel has been studied for safety in treating ovarian cancer, with Bevacizumab being used in various chemotherapy regimens. These studies suggest that the combination is generally safe, although specific side effects and risks should be discussed with a healthcare provider. ^{4 6 7 8 9}

How is the drug combination of Lurbinectedin, Paclitaxel, and Bevacizumab unique for ovarian cancer?

This drug combination is unique because it includes Lurbinectedin, which is not commonly used in standard ovarian cancer treatments. Lurbinectedin works by interfering with the cancer cell's DNA, while Bevacizumab targets blood vessels that supply the tumor, and Paclitaxel stops cancer cells from dividing, offering a multi-faceted approach to treatment. ^{4 6 10 11 12}

Research Team

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with ovarian, fallopian tube, or peritoneal carcinoma that's resistant to platinum-based treatments. Participants must be in good physical condition (ECOG 0-1), have had any number of prior therapies but no recent anti-cancer treatments, and not be pregnant or breastfeeding. They should not have serious heart issues, uncontrolled infections, significant bleeding disorders, or known allergies to the drugs being tested.

Inclusion Criteria

Ability to provide signed informed consent in accordance with federal, local, and institutional guidelines

I am fully active or can carry out light work.

I am 18 years old or older.

Exclusion Criteria

My heart condition is unstable.

I have not had major surgery in the last 4 weeks.

I have been treated with anti-VEGF therapy for platinum-resistant cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of paclitaxel, bevacizumab, and lurbinectedin to identify dose-limiting toxicities and recommended phase 2 dose

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of progression free survival and overall survival

12 months

Treatment Details

Interventions

• Bevacizumab
• Lurbinectedin
• Paclitaxel

Trial Overview The study tests if adding lurbinectedin to paclitaxel and bevacizumab can better control advanced ovarian cancer. It's a Phase 1b trial which means it’s early in testing this combination treatment and focuses on safety and how well patients tolerate the drug mix.

Participant Groups

Group I: Dose Escalation and Dose Expansion Experimental Treatment 3 Interventions

Pariticipants will be assigned to a dose level of combined paclitaxel, bevacizumab, and lurbinectedin

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

In a study involving patients with newly diagnosed advanced ovarian cancer, the combination of olaparib and bevacizumab significantly improved overall survival (OS) in patients with homologous recombination deficiency (HRD), showing a 5-year OS rate of 65.5% compared to 48.4% for those receiving placebo.

The safety profile of olaparib plus bevacizumab was favorable, with low and balanced incidences of serious conditions like myelodysplastic syndrome and acute myeloid leukemia between treatment groups, confirming its potential as a standard care option for HRD-positive ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ray-Coquard, I., Leary, A., Pignata, S., et al.[2023]

In a study of 90 ovarian cancer patients, the combination of bevacizumab with paclitaxel and carboplatin significantly improved treatment outcomes, with higher remission and disease control rates compared to those receiving only paclitaxel and carboplatin.

The combined treatment also led to lower levels of tumor markers CA199, CEA, and CA242 without increasing the risk of adverse effects, indicating it is a safe and effective option for improving patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients. Jiang, Q., Qian, H., Mei, L., et al.[2023]

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 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 806 patients with advanced ovarian cancer, the addition of maintenance olaparib to bevacizumab significantly improved progression-free survival, with a median of 22.1 months compared to 16.6 months for placebo, indicating its efficacy as a treatment option.

The benefit of olaparib was particularly pronounced in patients with homologous-recombination deficiency (HRD), showing a median progression-free survival of 37.2 months for those with BRCA mutations and 28.1 months for HRD-positive tumors without BRCA mutations, demonstrating its effectiveness regardless of BRCA status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. Ray-Coquard, I., Pautier, P., Pignata, S., et al.[2020]

In a study of 86 patients with platinum-resistant recurrent ovarian cancer, the combination of bevacizumab (BEV) and albumin-bound paclitaxel (ABP) significantly improved the overall response rate (ORR) to 86.0% compared to 62.8% for ABP alone, indicating enhanced treatment efficacy.

Patients receiving BEV + ABP also experienced longer progression-free survival (8.9 months vs. 6.7 months) and overall survival (16.3 months vs. 12.6 months) compared to those treated with ABP alone, with no significant increase in adverse reactions, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Bevacizumab Combined with Albumin-Bound Paclitaxel in the Treatment of Platinum-Resistant Recurrent Ovarian Cancer. Liu, B., An, R., Yu, J.[2020]

In a study of 41 women with recurrent ovarian cancer, the combination of bevacizumab and docetaxel showed a 6-month progression-free survival rate of 43.9%, indicating that this treatment can be effective for patients who have relapsed after platinum-based therapy.

The treatment was generally well-tolerated, with common side effects including gastrointestinal issues and fatigue, but no new unexpected toxicities were reported, suggesting it is a safe option for further investigation in recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy. Wenham, RM., Lapolla, J., Lin, HY., et al.[2021]

Recent advancements in ovarian cancer treatment have introduced several new options that show improved survival rates compared to historical data, marking a significant progress after decades of stagnation.

Three new PARP inhibitors (olaparib, rucaparib, niraparib) have been approved for ovarian cancer, providing new maintenance and recurrence treatment options, alongside expanded uses for bevacizumab in combination chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Therapies for Ovarian Cancer. O'Malley, DM.[2020]

The TURANDOT trial, involving 564 patients with HER2-negative metastatic breast cancer, demonstrated that bevacizumab plus capecitabine is non-inferior in overall survival compared to bevacizumab plus paclitaxel, with median survival times of 26.1 months and 30.2 months respectively.

Bevacizumab plus capecitabine showed a better safety profile, with significantly fewer cases of severe neutropenia and hand-foot syndrome compared to bevacizumab plus paclitaxel, making it a tolerable first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Zielinski, C., Láng, I., Inbar, M., et al.[2022]

Bevacizumab, when combined with carboplatin and paclitaxel, significantly prolongs progression-free survival in women with newly diagnosed advanced ovarian cancer, as shown in the GOG-0218 and ICON7 studies.

In patients with recurrent platinum-sensitive ovarian cancer, bevacizumab combined with carboplatin and gemcitabine also extends progression-free survival, demonstrating its efficacy in both first-line and second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Dhillon, S.[2019]

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]

In a case study of a 44-year-old woman with advanced epithelial ovarian cancer, the combination of bevacizumab with carboplatin and paclitaxel chemotherapy resulted in complete remission after 6 cycles of treatment, demonstrating the efficacy of this regimen.

The treatment was well-tolerated, with no serious side effects such as bone marrow suppression, hypertension, or proteinuria reported during bevacizumab administration, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report. Suwannarurk, K., Thaweekul, Y., Mairaing, K., et al.[2018]

References

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

Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. [2023]

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

Effect of bevacizumab plus paclitaxel and carboplatin regimen on prognostic survival of ovarian cancer patients. [2023]

3. 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]

4. Cyprus pubmed.ncbi.nlm.nih.gov

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

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

Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. [2020]

6. Cyprus pubmed.ncbi.nlm.nih.gov

Efficacy of Bevacizumab Combined with Albumin-Bound Paclitaxel in the Treatment of Platinum-Resistant Recurrent Ovarian Cancer. [2020]

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

A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy. [2021]

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

New Therapies for Ovarian Cancer. [2020]

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

Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. [2019]

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

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

12. Thailand pubmed.ncbi.nlm.nih.gov

Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report. [2018]