Chemotherapy + Targeted Therapy for Recurrent Ovarian Cancer

Overseen By Shannon Westin, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-VEGF therapy

Disqualifiers: Non-epithelial tumors, Active infection, 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: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for women with ovarian cancer that has returned and does not respond to standard platinum-based drugs. It examines the effectiveness of combining two medications, paclitaxel (a type of chemotherapy) and bevacizumab (a targeted therapy), and assesses whether adding a third drug, zoledronic acid, makes a difference. Women whose ovarian cancer has returned after one or two treatments and whose cancers do not respond to platinum are suitable candidates. The study aims to find better ways to manage and treat this type of cancer. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking advancements in ovarian cancer therapy.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that you cannot have received certain anticancer therapies within two weeks before starting the trial, and you cannot be on other anticancer treatments during the trial.

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

Research shows that both bevacizumab and paclitaxel are generally safe for treating ovarian cancer.

Bevacizumab is often used for recurrent ovarian cancer. Extensive studies have clarified its side effects, which are similar to those of other ovarian cancer treatments. Some patients might experience these side effects.

Paclitaxel is another common treatment for ovarian cancer with a well-established safety record. Although some patients might have allergic reactions, research indicates that different versions of paclitaxel can be safe even for those who have previously reacted.

In summary, both treatments have been widely used and studied, with well-documented safety. Always consult a healthcare provider about possible side effects and personal health conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for recurrent ovarian cancer because they combine chemotherapy with targeted therapy for a more precise attack on cancer cells. Bevacizumab is unique because it targets and inhibits a protein called VEGF, which is essential for the growth of blood vessels that supply tumors. This can potentially slow down or stop the growth of cancer. On the other hand, Paclitaxel works by interfering with the normal function of microtubules during cell division, effectively killing cancer cells. Unlike standard treatments that primarily focus on chemotherapy alone, this combination aims to enhance effectiveness by cutting off the tumor's blood supply while simultaneously attacking the cancer cells.

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

Studies have shown that paclitaxel, a treatment in this trial, can help treat recurrent ovarian cancer. In one study, half of the patients who received weekly paclitaxel showed noticeable improvement. Bevacizumab, another treatment option in this trial, has also shown promise when combined with chemotherapy. Research indicates that bevacizumab can delay cancer progression by more than six months. These treatments, in separate arms of the trial, aim to better manage ovarian cancer by attacking it in different ways. ^{6 7 8 9 10}

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 women over 18 with recurrent, platinum-resistant epithelial ovarian cancer who've had 1-2 prior treatments. They must have good performance status and organ function, not be pregnant or breastfeeding, and have no other active cancers or recent major surgeries. Participants should not have received certain therapies recently and must agree to contraception if applicable.

Inclusion Criteria

My ovarian cancer is resistant to platinum-based chemotherapy.

Adequate normal organ and marrow function as defined below: Hemoglobin ≥9.0 g/dL, Absolute neutrophil count (ANC) > 1500/mm3, Platelet count ≥100 x 10^9/L, Serum bilirubin ≤1.5 x ULN, AST (SGOT)/ALT (SGPT) ≤2.5 x ULN unless liver metastases are present, Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min, Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients

I am willing and able to follow the study's treatment plan and attend all visits.

Exclusion Criteria

I haven't had any other active cancers in the last 5 years.

My ovarian cancer is not the common type and includes specific rare forms.

Patients with conditions likely to increase gastrointestinal toxicity, History of bowel obstruction, Patients who are pregnant or lactating, Recent anticancer therapy, Major surgery within four weeks before Day 1, Unstable cardiovascular function, Uncontrolled infection, Active hepatitis A, B, or C infection, HIV seropositive, Conditions interfering with absorption of oral medication, Grade >2 peripheral neuropathy at baseline, Proteinuria >2+, Serious psychiatric or medical conditions, Participation in an investigational anti-cancer study within 3 weeks prior to Cycle 1 Day 1, Concurrent therapy with anticancer therapeutic other than steroids, Coagulation problems and active bleeding within 4 weeks prior to C1D1, Symptomatic brain lesions, Women not postmenopausal and not undergone surgical sterilization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly paclitaxel and bevacizumab with or without zoledronic acid

8 weeks

Weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Paclitaxel
• Zoledronic Acid

Trial Overview

The study compares weekly paclitaxel and bevacizumab (control) against the same regimen plus zoledronic acid (experimental) in women with specific types of ovarian cancer that's resistant to platinum-based chemotherapy. It's a randomized pilot trial where patients are assigned by chance to either group.

How Is the Trial Designed?

Group I: Paclitaxel Experimental Treatment 1 Intervention

Group II: Bevacizumab Experimental Treatment 1 Intervention

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+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Current standard treatment for ovarian cancer involves carboplatin and paclitaxel, but over 50% of patients experience relapse, highlighting the need for new therapies.

The Gynecologic Oncology Group is exploring innovative approaches, including the combination of bevacizumab with standard chemotherapy and various intraperitoneal chemotherapy regimens, to improve outcomes and reduce toxicity in patients with advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy for ovarian cancer: current status and new treatments. Ozols, RF.[2015]

Bevacizumab (Avastin) effectively targets VEGF to inhibit tumor angiogenesis, showing a safety profile that includes mostly mild to moderate side effects such as hypertension and proteinuria, which are manageable in clinical settings.

The side effects associated with bevacizumab, including rare but serious events like gastrointestinal perforation and arterial thrombosis, do not typically exacerbate the toxicity of standard chemotherapy, making it a suitable adjunct treatment for metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. Gordon, MS., Cunningham, D.[2015]

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 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 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 of 10 women with advanced, refractory ovarian cancer, treatment with biweekly bevacizumab and weekly taxane chemotherapy resulted in a decrease in CA125 levels for 9 out of 10 evaluable patients, indicating a positive response to therapy.

The treatment was well-tolerated, with mild side effects and no severe toxicities (grade 3 or 4), suggesting that this regimen is safe and warrants further investigation for its efficacy in managing symptoms of ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. Cohn, DE., Valmadre, S., Resnick, KE., et al.[2018]

A case study of a 39-year-old woman with recurrent breast cancer treated with bevacizumab and paclitaxel revealed a serious side effect: diverticular bleeding after the third treatment cycle.

The report suggests that bevacizumab may contribute to diverticular bleeding, highlighting the importance of assessing patient history for risk factors like diverticulitis and prior abdominal surgeries before starting this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diverticular Bleeding of the Colon during Combination Chemotherapy with Bevacizumab and Paclitaxel for Recurrent Breast Cancer. Nakayama, Y., Ito, Y., Tanabe, M., et al.[2021]

Citations

1.

avastin.com

avastin.com/hcp/ovar/efficacy-data.html

Avastin® (bevacizumab) Clinical Trials for Ovarian Cancer

Patients achieved a median PFS benefit of >6 months in stage III or IV ovarian cancer after primary surgery.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9160985/

Real-World Efficacy of Bevacizumab in Patients With ...

Bevacizumab in combination with chemotherapy prolonged the progression-free survival (PFS) of patients with recurrent epithelial ovarian cancer ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S0305737225000672

Optimal bevacizumab treatment strategy in advanced ...

Exploratory analysis demonstrated a clinically meaningful 10.2-month median OS improvement with maintenance bevacizumab versus chemotherapy alone in patients ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12149230/

Bevacizumab in recurrent epithelial ovarian cancer

Our study demonstrated that the addition of bevacizumab with commonly used chemotherapy significantly improved PFS and ORR among Indian women with recurrent ...

5.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2807928

Time-Dependent Changes in Risk of Progression During ...

In ovarian cancer, bevacizumab may reduce progression for approximately 1 year after initiation, but discontinuation may increase subsequent progression.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10003828/

Safety Analysis of Bevacizumab in Ovarian Cancer Patients

During surveillance after the standard treatment for EOC, the recurrence rate is about 75%, and most relapses and cancer deaths are related to ...

7.

avastin.com

avastin.com/hcp.html

Avastin® (bevacizumab) Efficacy, Safety, Dosing & ...

Ovarian cancer data are based on recurrent OC only; Avastin is also ... The safety data was consistent with the known safety profile established in ...

8.

avastin.com

avastin.com/hcp/ovar/safety.html

Avastin® (bevacizumab) Adverse Events | Ovarian Cancer

Learn more about Avastin® (bevacizumab) adverse reactions profile for stage III or IV ovarian cancer, platinum-sensitive ovarian cancer (psOC) ...

9.

sciencedirect.com

sciencedirect.com/science/article/pii/S0090825825000915

Comparative efficacy and safety of low-dose versus high ...

Despite limitations of small sample size and heterogeneities, findings suggest that bevacizumab dose may not significantly impact ovarian cancer outcomes.

10.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK594396/

Bevacizumab for Recurrent Platinum-Sensitive Ovarian Cancer

Bevacizumab was described by both of the RCT reports included in this review as having a known safety profile,, and has been described in other literature as a ...