Letrozole +/- Chemotherapy for Ovarian Cancer

Recruiting at 827 trial locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: NRG Oncology

Must not be taking: Hormonal therapy

Disqualifiers: Severe cardiac disease, CNS metastases, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase III trial studies how well letrozole with or without paclitaxel and carboplatin works in treating patients with stage II-IV low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. Letrozole is an enzyme inhibitor that lowers the amount of estrogen made by the body which in turn may stop the growth of tumor cells that need estrogen to grow. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. It is not yet known whether giving letrozole alone or in combination with paclitaxel and carboplatin works better in treating patients with low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum compared to paclitaxel and carboplatin without letrozole.

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.

What data supports the idea that Letrozole +/- Chemotherapy for Ovarian Cancer is an effective drug?

The available research shows that combining paclitaxel with carboplatin, which is part of the Letrozole +/- Chemotherapy treatment, can improve survival rates for ovarian cancer patients. For example, one study found a 7% increase in survival and a 10% increase in the time patients lived without the cancer getting worse when using this combination compared to just using carboplatin alone. This suggests that the treatment can be more effective than some alternatives. ^{1 2 3 4 5}

What safety data exists for Letrozole and chemotherapy in ovarian cancer treatment?

The safety data for chemotherapy involving paclitaxel and carboplatin in ovarian cancer treatment shows that this combination is widely accepted and can be administered with an acceptable toxicity profile. Major toxicities include neutropenia, thrombocytopenia, and peripheral neuropathy, but these are generally manageable. Paclitaxel-associated hypersensitivity was noted but did not prevent continuation of treatment. The combination has shown significant antineoplastic activity and is considered a standard treatment for ovarian cancer. ^{6 7 8 9 10}

Is the drug Letrozole, Paclitaxel, Carboplatin a promising treatment for ovarian cancer?

The combination of Paclitaxel and Carboplatin is a standard and effective treatment for ovarian cancer, often improving quality of life. Letrozole, known as Femara, is not specifically highlighted in the research, but the combination with Paclitaxel and Carboplatin could be promising based on the effectiveness of these drugs in treating ovarian cancer. ^{3 4 6 11 12}

Research Team

Amanda N Fader

Principal Investigator

NRG Oncology

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Letrozole (Aromatase Inhibitor)
• Paclitaxel, Carboplatin (Alkylating agents, Anti-metabolites)

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.

Participant Groups

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 Canada for the following indications:

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+

Findings from Research

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]

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]

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 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]

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 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]

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]

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]

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 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]

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]

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]

References

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

The "Leuven" paclitaxel/carboplatin weekly regimen in patients with recurrent ovarian cancer, a retrospective study. [2019]

2. United States 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. [2019]

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

Treatment of ovarian cancer: current status. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer. [2018]

5. England 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. [2018]

6. United States 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). [2015]

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

Carboplatin plus paclitaxel weekly dose-dense chemotherapy for high-grade ovarian cancer: A re-evaluation. [2021]

8. England 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]

9. England pubmed.ncbi.nlm.nih.gov

USA update on paclitaxel in ovarian cancer. [2019]

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

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience. [2015]

11. Germany pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. [2008]

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

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