Durvalumab + Chemotherapy for Ovarian Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Carboplatin, Paclitaxel

Must not be taking: Immunosuppressants

Disqualifiers: Autoimmune disease, Organ transplant, others

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

Compensation: Varies

Number of Visits: 44

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies how well durvalumab works when given in combination with carboplatin and paclitaxel in treating patients with stage III-IV ovarian, primary peritoneal, or fallopian tube cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving durvalumab in combination with carboplatin and paclitaxel may be a better treatment for ovarian, primary peritoneal, or fallopian tube cancer.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 28 days before starting the trial, except for certain low-dose corticosteroids. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Durvalumab and chemotherapy for ovarian cancer?

Research shows that the combination of paclitaxel and carboplatin is effective in treating advanced ovarian cancer, with studies indicating it is better tolerated and easier to administer than other combinations. Additionally, paclitaxel has been shown to be highly active in patients with platinum-resistant ovarian cancer, suggesting its potential effectiveness in combination therapies. ^{1 2 3 4 5}

Is the combination of Durvalumab and chemotherapy safe for humans?

The combination of Durvalumab with chemotherapy has been studied in various cancers, showing that most side effects are mild to moderate, such as diarrhea, skin issues, and thyroid problems. However, some serious side effects like pneumonitis (lung inflammation) and myocarditis (heart inflammation) have occurred, and there were two treatment-related deaths in one study. ^{6 7 8 9 10}

What makes the drug combination of Durvalumab, Carboplatin, and Paclitaxel unique for treating ovarian cancer?

This treatment is unique because it combines Durvalumab, an immune checkpoint inhibitor that blocks PD-L1, with standard chemotherapy drugs Carboplatin and Paclitaxel, potentially enhancing the immune system's ability to fight ovarian cancer and improving progression-free survival. ^{10 11 12 13 14}

Research Team

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for women with advanced stage III-IV ovarian, primary peritoneal, or fallopian tube cancer who haven't had previous treatments. They should have good blood counts and organ function, not be pregnant or breastfeeding, and willing to follow the study plan. Excluded are those with certain medical conditions like uncontrolled seizures, prior immunotherapy with PD1/PD-L1 inhibitors including durvalumab, unresolved toxicities from past cancer therapies, active infections or autoimmune diseases.

Inclusion Criteria

I haven't received any treatment for my advanced ovarian, peritoneal, or fallopian tube cancer.

I am willing and able to follow the study's requirements, including treatments and visits.

I have a tumor sample available for research before any treatment.

Exclusion Criteria

I have had an autoimmune disease in the last 2 years.

You have a history of a weak immune system since birth.

You have had a bad reaction to durvalumab or any of its ingredients in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive durvalumab and carboplatin IV on day 1, and paclitaxel IV on days 1, 8, and 15. Treatment repeats every 21 days for up to 3 courses.

9 weeks

3 cycles of treatment

Surgery

Participants undergo debulking laparoscopic surgery after 3 courses of chemotherapy.

1 week

1 surgical visit

Adjuvant Therapy

Participants receive carboplatin, paclitaxel, and durvalumab IV. Treatment repeats every 21 days for up to 3 courses.

9 weeks

3 cycles of treatment

Maintenance Therapy

Participants receive durvalumab IV on day 1 and 15. Treatment repeats every 28 days for up to 7 courses.

28 weeks

7 cycles of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

12 months

Follow-up visits at 30 days, 2, 3, 4, 6, 8, 9, 10, and 12 months, then every 6 months

Treatment Details

Interventions

• Carboplatin
• Durvalumab
• Paclitaxel

Trial Overview The N-Dur trial is testing how well the combination of durvalumab (an immunotherapy drug) works alongside chemotherapy drugs carboplatin and paclitaxel in treating patients. It's a phase I/II study aiming to see if this mix can better help the immune system attack cancer cells and prevent their growth and spread.

Participant Groups

Group I: Treatment (durvalumab, carboplatin, paclitaxel, questionnaire) Experimental Treatment 6 Interventions

NEOADJUVANT CHEMOTHERAPY: Before debulking surgery, patients receive durvalumab and carboplatin IV over 1 hour on day 1, and paclitaxel IV over 3 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo debulking surgery. SURGERY: After 3 courses of chemotherapy, patients undergo debulking laparoscopic surgery. ADJUVANT THERAPY: Beginning after debulking surgery, patients receive carboplatin IV over 1 hour on day 1, paclitaxel IV over 3 hours on days 1, 8, and 15, and durvalumab IV over 1 hour on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive durvalumab IV over 1 hour on day 1 and 15. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

In advanced ovarian cancer, the combination of paclitaxel and carboplatin is the standard first-line treatment, showing effectiveness comparable to paclitaxel and cisplatin, while being better tolerated by patients.

For recurrent ovarian cancer, recent trials suggest that paclitaxel/carboplatin may be more effective than single-agent carboplatin, highlighting the importance of ongoing research into new treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced ovarian cancer: a clinical update on first-line treatment, recurrent disease, and new agents. Ozols, RF.[2022]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a Phase I/II trial involving 59 patients with stages I-III triple-negative breast cancer, the combination of durvalumab with chemotherapy resulted in a pathologic complete response (pCR) rate of 44%, indicating its potential efficacy as a neoadjuvant treatment.

The study found that higher levels of stromal tumor-infiltrating lymphocytes (sTILs) were associated with better pCR rates, suggesting that immune response may play a role in treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. Foldi, J., Silber, A., Reisenbichler, E., et al.[2022]

In a phase Ib study involving 136 patients, durvalumab (Du) combined with tremelimumab (Tr) and standard platinum-doublet chemotherapy was found to be safe, with most drug-related adverse events being mild (≤ grade 2) and primarily due to chemotherapy.

Among 73 patients with non-small cell lung cancer (NSCLC), the treatment achieved a 51% objective response rate, with a median progression-free survival of 6.5 months and overall survival of 19.8 months, indicating promising efficacy comparable to other immunotherapy and chemotherapy combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. Juergens, RA., Hao, D., Ellis, PM., et al.[2021]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

This phase II study aims to evaluate the effectiveness of combining durvalumab and tremelimumab with neoadjuvant chemotherapy in improving progression-free survival (PFS) in patients with advanced-stage ovarian cancer, specifically those with stage IIIC/IV epithelial ovarian cancer.

The study will involve 24 patients and will assess immune biomarkers and changes in the tumor microenvironment through serial biopsies, with the primary goal of achieving a 12-month PFS rate, while also monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D. Lee, JY., Kim, JW., Lim, MC., et al.[2020]

The combination of the FRα vaccine TPIV200 and the PD-L1 inhibitor durvalumab was well tolerated in 27 patients with advanced platinum-resistant ovarian cancer, showing a low grade 3 toxicity rate of 18.5%.

While the overall response rate was low (3.7% partial response and 33.3% stable disease), the median overall survival was notably long at 21 months, suggesting potential benefits from this immunotherapy approach in a heavily pretreated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial. Zamarin, D., Walderich, S., Holland, A., et al.[2021]

References

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

Antitumor Effect of Nivolumab on Subsequent Chemotherapy for Platinum-Resistant Ovarian Cancer. [2019]

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

Treatment of ovarian cancer: current status. [2015]

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

Ifosfamide, paclitaxel and cisplatin first-line chemotherapy in advanced, suboptimally debulked epithelial ovarian cancer. [2019]

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

Advanced ovarian cancer: a clinical update on first-line treatment, recurrent disease, and new agents. [2022]

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

Carboplatin plus ifosfamide as salvage treatment of epithelial ovarian cancer: a pilot study. [2017]

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

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

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

Type of chemotherapy has substantial effects on the immune system in ovarian cancer. [2023]

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

Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Results of a Phase Ib Study Investigating Durvalumab in Combination with Eribulin in Patients with HER2-negative Metastatic Breast Cancer and Recurrent Ovarian Cancer. [2023]

10. Ireland pubmed.ncbi.nlm.nih.gov

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. [2021]

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

Phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer: primary analysis in the original cohort of KGOG3046/TRU-D. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

13. Korea (South) pubmed.ncbi.nlm.nih.gov

A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D. [2020]

14. England pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial. [2021]