Letrozole +/- Chemotherapy for Ovarian Cancer

Not currently recruiting at 1055 trial locations

Overseen By Patrick W. Cobb

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: NRG Oncology

Must not be taking: Hormonal therapy

Disqualifiers: Severe cardiac disease, CNS metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of letrozole, with or without additional chemotherapy drugs, in treating low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. Letrozole lowers estrogen levels, potentially stopping tumor growth, while the chemotherapy drugs aim to kill or prevent the spread of cancer cells. The trial compares the effectiveness of letrozole alone versus in combination with chemotherapy drugs. It is designed for individuals newly diagnosed with stage II-IV low-grade serous ovarian cancer who have undergone surgery to remove the ovaries and fallopian tubes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received previous chemotherapy, radiotherapy, or hormonal therapy for this disease.

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

Research has shown that letrozole, a drug used to lower estrogen levels, has generally been well-tolerated in past studies. In one study, 55.5% of patients took letrozole, and only a few experienced a return of cancer or passed away during the follow-up period. This suggests that letrozole is relatively safe, with few serious side effects reported.

Earlier research found that patients responded well to the combination of paclitaxel and carboplatin used with letrozole. Although this combination is often used in cancer treatments, patients may experience side effects like nausea, tiredness, and low blood cell counts. However, proper medical care usually manages these side effects.

Overall, both letrozole alone and with paclitaxel and carboplatin have been shown to be safe for many patients, with side effects that are typically controllable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for ovarian cancer, which often involve chemotherapy alone, this study explores the combination of letrozole, a hormone therapy, with chemotherapy drugs paclitaxel and carboplatin. Letrozole is unique because it works by reducing the production of estrogen, which can fuel the growth of some ovarian cancers. Researchers are excited about this approach because combining letrozole with chemotherapy could potentially enhance the effectiveness of treatment, offering a more targeted attack on cancer cells. Additionally, letrozole is taken orally, which may provide a more convenient option compared to some intravenous treatments.

What evidence suggests that this trial's treatments could be effective for low-grade serous carcinoma?

Research has shown that letrozole, a type of medication, can help manage ovarian cancer by lowering estrogen levels, potentially slowing tumor growth. Studies have found that letrozole can extend periods without cancer progression, with generally manageable side effects. In one study, 45% of patients experienced stable disease, meaning their cancer did not worsen for a significant time.

In this trial, one group of participants will receive letrozole alone, while another group will receive letrozole combined with the chemotherapy drugs paclitaxel and carboplatin. Early findings suggest that 79% of patients benefit from this combination, with 79% not experiencing cancer progression for three years. This combination may enhance treatment effectiveness for low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. ^{2 6 7 8 9}

Who Is on the Research Team?

Amanda N Fader

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with stage II-IV low-grade serous ovarian, fallopian tube, or primary peritoneal cancer. They must have had surgery to remove the cancer and be able to take oral medications. People can't join if they've had chemotherapy or radiotherapy for this disease before, are allergic to letrozole or carboplatin/paclitaxel, have severe heart issues, brain metastases, uncontrolled infections, significant neuropathy or untreated HIV.

Inclusion Criteria

Your creatinine levels are not too high, as checked within 14 days before enrolling in the study.

I have another cancer, but it won't affect this trial's treatment.

I have been newly diagnosed with stage II-IV low-grade serous ovarian, fallopian tube, or primary peritoneal cancer.

Exclusion Criteria

I do not have any serious or uncontrolled infections, except for a simple UTI.

I am HIV positive, on treatment, and my viral load is undetectable.

I have not had a heart attack or unstable heart pain in the last 6 months and do not have severe heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive paclitaxel and carboplatin IV every 21 days for up to 6 cycles, followed by letrozole maintenance therapy

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 years

Every 3 months for 1 year, then every 6 months for 3 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole
• Paclitaxel, Carboplatin

Trial Overview

The study is testing whether letrozole alone or combined with chemotherapy drugs paclitaxel and carboplatin is more effective in treating certain types of gynecological cancers compared to just chemotherapy. Letrozole lowers estrogen which may stop tumor growth; chemo kills or stops the spread of cancer cells.

How Is the Trial Designed?

Group I: Arm II (letrozole) Experimental Treatment 4 Interventions

Patients receive letrozole PO QD. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally PO QD in the absence of disease progression or unacceptable toxicity as maintenance therapy. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

Group II: Arm I (paclitaxel, carboplatin, letrozole) Experimental Treatment 6 Interventions

Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.

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

Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

Approved in Canada as Letrozole for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 study involving 2074 women with ovarian cancer, the combination of paclitaxel and carboplatin did not show a significant improvement in overall survival compared to control treatments (CAP or carboplatin alone), with median survival times being very similar (36.1 months vs. 35.4 months).

While paclitaxel plus carboplatin resulted in more side effects like alopecia and sensory neuropathy compared to carboplatin alone, the overall effectiveness of single-agent carboplatin was comparable, suggesting it could be a safer first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. [2022]

Docetaxel has shown comparable effectiveness to paclitaxel when combined with carboplatin for treating advanced ovarian cancer, with a potentially better safety profile.

Current treatments for platinum-resistant ovarian cancer are limited, and while some experimental therapies targeting the epidermal growth factor receptor show promise, more research is needed to find effective new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. Costa, SD., von Minckwitz, G., Wernicke, K., et al.[2008]

In a study of 246 patients with advanced ovarian cancer, those receiving a dose-dense weekly paclitaxel regimen showed significantly better progression-free survival (22 months) compared to those on standard 3-weekly chemotherapy (15 months).

While the dose-dense protocol also suggested improved overall survival (66 months vs. 54 months), this difference was not statistically significant, and patients experienced higher rates of side effects, including gastrointestinal and neurological issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin plus paclitaxel weekly dose-dense chemotherapy for high-grade ovarian cancer: A re-evaluation. Kessous, R., Matanes, E., Laskov, I., et al.[2021]

Patients with ovarian cancer who relapse more than 6 months after platinum-based chemotherapy can benefit from repeat chemotherapy with carboplatin, especially when combined with paclitaxel, which showed a 7% increase in survival and a 10% increase in progression-free survival in a trial of 802 patients.

The combination treatment resulted in higher rates of certain side effects, such as significant hair loss and neurotoxicity, indicating that while the combination is more effective, it also comes with increased toxicity compared to carboplatin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of platinum-sensitive relapsed ovarian cancer, with particular reference to the International Collaboration in Ovarian Neoplasm-4/Arbeitsgemeinschaft Gynakologische Onkologie Ovarian Cancer-2.2 trial. Kaye, SB.[2018]

In a phase 2 study involving 35 women with recurrent epithelial ovarian cancer, the combination of belinostat, carboplatin, and paclitaxel showed a promising overall response rate of 43%, indicating potential efficacy in heavily-pretreated patients.

The treatment was generally well tolerated, with common side effects including nausea (83%) and fatigue (74%), and a 6-month progression-free survival rate of 48%, suggesting that this combination therapy could be a viable option for patients with challenging cases of ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer. Dizon, DS., Damstrup, L., Finkler, NJ., et al.[2018]

In a trial involving 59 women with advanced ovarian cancer, the combination of paclitaxel and carboplatin resulted in a high response rate of 72%, indicating effective treatment for this patient population.

Patients experienced significant improvements in quality of life during the outpatient treatment, with median survival times of 30.1 months for those with measurable disease, suggesting that this regimen is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient taxol and carboplatin chemotherapy for suboptimally debulked epithelial carcinoma of the ovary results in improved quality of life: an Eastern Cooperative Oncology Group Phase II Study (E2E93). Schink, JC., Weller, E., Harris, LS., et al.[2015]

Paclitaxel has recently become a standard chemotherapy treatment for advanced ovarian cancer, especially when combined with platinum compounds, based on a large randomized trial by the Gynaecologic Oncology Group.

Ongoing clinical trials are investigating the optimal use of paclitaxel, including its dosage, administration schedule, and comparing the effectiveness and side effects of different platinum combinations (carboplatin vs. cisplatin).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

USA update on paclitaxel in ovarian cancer. Ozols, RF.[2019]

The weekly regimen of paclitaxel and carboplatin showed a response rate of 37% in patients with recurrent ovarian cancer, demonstrating its efficacy, especially in those with platinum-resistant disease.

The treatment had a manageable toxicity profile, with the most common side effects being bone marrow-related issues like neutropenia, affecting 67% of patients, and requiring dose reductions in 24% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The "Leuven" paclitaxel/carboplatin weekly regimen in patients with recurrent ovarian cancer, a retrospective study. Cadron, I., Abdulkadir, L., Despierre, E., et al.[2019]

The combination of carboplatin and 3-hour infusional paclitaxel was well-tolerated in a study of 92 women with advanced gynecologic cancers, showing a manageable toxicity profile with neutropenia being the most significant side effect.

In patients with ovarian cancer or primary peritoneal carcinoma, 74% experienced a significant decline in tumor marker levels after treatment, indicating strong antineoplastic activity of this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. Markman, M., Kennedy, A., Webster, K., et al.[2015]

In a phase II trial involving 53 women with stage IV ovarian cancer, a novel treatment strategy combining modified chemotherapy and maintenance therapy with paclitaxel resulted in a 2-year overall survival rate of 48%, which is lower than the 60% survival rate of a historical control group treated with standard therapy.

The study highlighted the feasibility of adjusting treatment based on patient response, but ultimately concluded that this specific approach does not warrant further investigation due to its survival outcomes not being superior to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of single agent carboplatin followed by dose-intense paclitaxel, followed by maintenance paclitaxel therapy in stage IV ovarian, fallopian tube, and peritoneal cancers: a Southwest Oncology Group trial. Markman, M., Glass, T., Smith, HO., et al.[2019]

Docetaxel combined with carboplatin is a feasible and tolerable first-line treatment option for newly diagnosed epithelial ovarian cancer, showing no significant difference in progression-free or overall survival compared to the traditional paclitaxel and carboplatin combination in a study of 1,077 patients.

While docetaxel was associated with more myelosuppression, it resulted in fewer cases of neuropathy compared to paclitaxel, leading to better quality-of-life outcomes for patients receiving docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of docetaxel in the treatment of newly diagnosed advanced ovarian cancer. Vasey, PA.[2018]

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