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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for late-stage ovarian, primary peritoneal, or fallopian tube cancer. It examines how well the immunotherapy drug durvalumab works with standard chemotherapy drugs, carboplatin and paclitaxel, to help the body fight cancer and stop tumor growth. The trial targets individuals with high-grade forms of these cancers who have not yet received treatment. Participants will receive the drug combination before surgery and continue with the treatment afterward to assess its effectiveness in managing their cancer. 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 combination therapy.

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.

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

Research has shown that durvalumab is generally safe for patients with various solid cancers. Studies have found it to have a manageable safety profile when used alone or with tremelimumab.

Carboplatin, a common chemotherapy drug, is well-tolerated, even by older patients with ovarian cancer. It is often combined with paclitaxel to treat ovarian cancer. This combination has proven effective and safe, even for patients with recurrent cancer after previous treatments.

Paclitaxel also has a good safety record and works well with platinum-based drugs like carboplatin. Studies suggest it is effective and can be safely administered, even to patients who previously experienced allergic reactions.

Overall, these treatments are considered safe based on previous research. However, this trial remains in the early stages. Early-phase trials focus on ensuring treatments are safe and determining the right dosage. While the data is promising, more research is needed to confirm safety in this specific combination. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for ovarian cancer?

Researchers are excited about this treatment combination for ovarian cancer because it integrates durvalumab, an immunotherapy drug, with standard chemotherapy agents like carboplatin and paclitaxel. Unlike traditional treatments that mainly focus on killing cancer cells directly, durvalumab boosts the body's immune system to recognize and attack cancer cells more effectively. This combination has the potential to enhance the overall treatment response by not only targeting cancer cells but also by engaging the immune system, which could lead to improved outcomes for patients. This approach represents a promising shift in how ovarian cancer is treated, offering hope for more durable and effective responses.

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

Research has shown that durvalumab can help people with ovarian cancer live longer without disease progression. In this trial, participants will receive a combination of durvalumab, carboplatin, and paclitaxel. Durvalumab boosts the immune system to fight cancer cells, potentially stopping their growth and spread. Meanwhile, carboplatin and paclitaxel, well-known chemotherapy drugs for ovarian cancer, work by killing cancer cells or preventing their multiplication. Together, these treatments might offer a more effective approach to treating advanced ovarian and related cancers. ^{1 5 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

Citations

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Efficacy and Safety of First-line Single-Agent Carboplatin ... At the data cutoff date, 76 patients (63%) had died, most (56 of 76 [74%]) from ovarian cancer. Median OS was not reached (95% CI, 21.0-32.2 ...

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Efficacy and safety of the paclitaxel and carboplatin ... Conclusion: This combined paclitaxel-carboplatin therapy is effective and can be safely administered to ovarian cancer patients who relapse after one or two ...

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Efficacy and safety of paclitaxel liposome versus ... The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy.

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Weekly vs. Every-3-Week Paclitaxel and Carboplatin for ... In conclusion, our data suggest that weekly paclitaxel did not prolong progression-free survival, as compared with paclitaxel administered every ...

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Results of combined therapy with pemetrexed and ... A retrospective study evaluated the efficacy of combined therapy with pemetrexed and carboplatin in 15 patients with progressive ovarian cancer.

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A multicenter retrospective study to assess feasibility ... Our data demonstrates that standard 3wCP is a well-tolerated, feasible first-line treatment for frail, elderly ovarian cancer patients.

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Efficacy and Safety of Paclitaxel and Carboplatin for ... Conclusion. Current evidence suggests that paclitaxel and carboplatin do not produce more satisfactory results with respect to overall survival ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)55138-9/fulltext

Efficacy and safety of the paclitaxel and carboplatin ... Response rates for platinum-refractory patients and those with early (≥3 and <12 months) and late (>12 months) relapses were 24%, 33% and 70%, respectively. The ...