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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding lurbinectedin to a combination of paclitaxel and bevacizumab (also known as Avastin) can better control advanced ovarian cancer. Participants will receive varying doses of these drugs to identify the most effective and safe levels. This trial may suit individuals with ovarian, fallopian tube, or peritoneal cancer who have experienced limited success with previous treatments, including those whose cancer did not respond well to platinum-based therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that lurbinectedin, one of the treatments under study, can cause serious side effects. In previous studies, many patients experienced severe neutropenia, a low white blood cell count, and febrile neutropenia, a fever combined with a low white blood cell count. These conditions are crucial to monitor because they can weaken the body's ability to fight infections.

Paclitaxel, another treatment in the trial, has shown safety in other studies. It is generally well-tolerated, even by patients who previously had allergic reactions to it, suggesting it can be used safely in various situations.

Bevacizumab, the third treatment, also has a good track record. Studies have shown it significantly improves progression-free survival, the period when cancer does not worsen, in ovarian cancer. It is usually well-tolerated, but patients should be aware of possible side effects like high blood pressure.

Since this trial is in its early stages, more research is needed to fully understand how these treatments work together. However, existing data provides a helpful starting point for assessing their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for ovarian cancer, which often involve surgery and chemotherapy drugs like carboplatin and paclitaxel, this new combination treatment brings in lurbinectedin and bevacizumab for a unique approach. Lurbinectedin is a novel drug that targets the transcription process in cancer cells, disrupting their ability to grow and spread. Bevacizumab, on the other hand, works by inhibiting blood vessel growth that tumors need to thrive. Researchers are excited because combining these mechanisms with paclitaxel may enhance effectiveness and offer a new avenue for tackling ovarian cancer more aggressively.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown that lurbinectedin may effectively treat ovarian cancer, particularly when the cancer resists platinum-based treatments. Studies have found it to outperform traditional options like cisplatin, offering better response rates and longer survival times. Paclitaxel, often combined with other medications, can delay cancer progression by several months. Bevacizumab has also proven effective, allowing patients to live without cancer progression for more than six months in advanced cases. Adding bevacizumab to treatment plans has improved overall survival for many patients. In this trial, participants will receive a combination of lurbinectedin, paclitaxel, and bevacizumab, which together have shown potential in managing advanced ovarian cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 have had multiple treatments for my condition.

Exclusion Criteria

My heart condition is unstable.

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

I haven't had cancer treatment like radiation or chemotherapy in the last 2 weeks.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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 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]

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 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]

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]

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]

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