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

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized pilot trial of weekly paclitaxel and bevacizumab with or without zoledronic acid in women with platinum-resistant epithelial ovarian cancer with 1-2 prior regimens for recurrence.

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.

What data supports the effectiveness of the drug combination used in the clinical trial for recurrent ovarian cancer?

Research shows that combining bevacizumab (a drug that stops blood vessel growth in tumors) with albumin-bound paclitaxel (a type of chemotherapy) can be effective in treating recurrent ovarian cancer, especially when the cancer is resistant to platinum-based treatments. ^{1 2 3 4 5}

Is the combination of chemotherapy and targeted therapy safe for humans?

The combination of bevacizumab (Avastin) and paclitaxel (Taxol) has been studied for safety in various conditions, including ovarian and breast cancer. Common side effects include high blood pressure, protein in urine, and minor bleeding, which are usually mild and manageable. Rarely, more serious issues like wound healing problems and gastrointestinal perforations can occur. ^{2 6 7 8 9}

How is the drug combination of Bevacizumab and Paclitaxel unique for treating recurrent ovarian cancer?

This drug combination is unique because Bevacizumab, a targeted therapy, is used alongside Paclitaxel to improve progression-free survival in patients with recurrent ovarian cancer, especially those resistant to platinum-based treatments. Bevacizumab works by inhibiting blood vessel growth in tumors, which is different from traditional chemotherapy approaches. ^{1 2 10 11 12}

Research Team

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 (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]

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]

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]

References

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

Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma. [2020]

2. Cyprus pubmed.ncbi.nlm.nih.gov

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

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

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

4. 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]

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

Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. [2018]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. [2015]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Diverticular Bleeding of the Colon during Combination Chemotherapy with Bevacizumab and Paclitaxel for Recurrent Breast Cancer. [2021]

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

Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. [2023]

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

Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. [2020]

11. France pubmed.ncbi.nlm.nih.gov

[Chemotherapy in epithelial ovarian cancer]. [2019]

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

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