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NCT04095364 · CITED IN SOURCE DOCUMENTS

Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-03-24

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * Patients must have newly diagnosed, stage II-IV low-grade serous ovarian cancer (submission of pathology report\[s\] required). Ovarian cancer = ovarian, fallopian tube and primary peritoneal cancers * NOTE: Patients with a prior history of serous borderline tumors but a new diagnosis of stage II-IV low-grade serous ovarian cancer are eligible * p53 immunohistochemistry (IHC) is required and must show nonaberrant pattern (nonaberrant p53 expression is consistent with normal/wildtype TP53) * A copy of the pathology report that includes the diagnosis of low grade serous ovarian cancer and nonaberrant p53 IHC result must be submitted in RAVE. NOTE: If aberrant p53 expression is found on p53 IHC, the patient is NOT eligible (aberrant p53 expression is consistent with mutant TP53 and supports diagnosis of high grade serous ovarian cancer) * Appropriate stage for study entry based on the following diagnostic workup: * History/physical examination within 14 days prior to registration; * Radiographic tumor assessment within 28 days prior to registration. (23-MAY-2023) * Age \>= 18 * Patients must have undergone an attempt at maximal upfront cytoreductive surgery, with either optimal (=\< 1 cm diameter residual disease/nodule) or suboptimal residual disease (\> 1 cm diameter residual disease/nodule) status allowed * Patients must have undergone a bilateral salpingo-oophorectomy * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to registration * Patients must be within =\< 8 weeks of primary cytoreductive surgery at time of randomization * Patients must be able to take per oral (P.O.) medications * Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl (within 14 days prior to registration) * Platelets greater than or equal to 100,000 cells/mcl (within 14 days prior to registration) * Creatinine less than or equal to 1.5 x upper limit of normal (ULN) (within 14 days prior to registration) * Bilirubin less than or equal to 1.5 x ULN (within 14 days prior to registration) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 x ULN (within 14 days prior to registration) * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial Exclusion Criteria: * Patients may not have received neoadjuvant or adjuvant chemotherapy or radiotherapy for the treatment of this disease * Patients may not have received previous hormonal therapy for the treatment of this disease * Patients with known hypersensitivity to letrozole or hypersensitivity/intolerance to carboplatin/paclitaxel therapy * Patients with severe cardiac disease: * Myocardial infarction or unstable angina within 6 months prior to registration * New York Heart Association (NYHA) class II or greater congestive heart failure * Patients with known central nervous system metastases * Patients with active (except for uncomplicated urinary tract infection) or uncontrolled systemic infection * Patients with \>= grade 2 baseline neuropathy * Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
healthy Volunteers
false
minimum Age
18 Years
sex
FEMALE
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Procedure: Biopsy Procedure
    2. Procedure: Biospecimen Collection
    3. Drug: Carboplatin
    4. Procedure: Imaging Procedure
    5. Drug: Letrozole
    6. Drug: Paclitaxel
    label
    Arm I (paclitaxel, carboplatin, letrozole)
    type
    EXPERIMENTAL
  2. description
    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.
    intervention Names
    1. Procedure: Biopsy Procedure
    2. Procedure: Biospecimen Collection
    3. Procedure: Imaging Procedure
    4. Drug: Letrozole
    label
    Arm II (letrozole)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I (paclitaxel, carboplatin, letrozole)
    2. Arm II (letrozole)
    description
    Undergo tumor biopsy
    name
    Biopsy Procedure
    other Names
    1. Biopsy
    2. BIOPSY_TYPE
    3. Bx
    type
    PROCEDURE
  2. arm Group Labels
    1. Arm I (paclitaxel, carboplatin, letrozole)
    2. Arm II (letrozole)
    description
    Undergo blood sample collection
    name
    Biospecimen Collection
    other Names
    1. Biological Sample Collection
    2. Biospecimen Collected
    3. Specimen Collection
    type
    PROCEDURE
  3. arm Group Labels
    1. Arm I (paclitaxel, carboplatin, letrozole)
    description
    Given IV
    name
    Carboplatin
    other Names
    1. Blastocarb
    2. Carboplat
    3. Carboplatin Hexal
    4. Carboplatino
    5. Carboplatinum
    6. Carbosin
    7. Carbosol
    8. Carbotec
    9. CBDCA
    10. Displata
    11. Ercar
    12. JM-8
    type
    DRUG
  4. arm Group Labels
    1. Arm I (paclitaxel, carboplatin, letrozole)
    2. Arm II (letrozole)
    description
    Undergo medical imaging
    name
    Imaging Procedure
    other Names
    1. Diagnostic Imaging Technique
    2. Image Type
    3. Imaging
    4. Imaging (procedure)
    5. Imaging Procedures
    6. Imaging Technique
    7. imaging type
    8. IMAGING_METHOD
    9. imaging_type
    10. Medical Imaging
    11. Type of imaging
    type
    PROCEDURE
  5. arm Group Labels
    1. Arm I (paclitaxel, carboplatin, letrozole)
    2. Arm II (letrozole)
    description
    Given PO
    name
    Letrozole
    other Names
    1. CGS 20267
    2. CGS-20267
    3. CGS20267
    4. Femara
    5. Fempro
    type
    DRUG
  6. arm Group Labels
    1. Arm I (paclitaxel, carboplatin, letrozole)
    description
    Given IV
    name
    Paclitaxel
    other Names
    1. Anzatax
    2. Asotax
    3. Bristaxol
    4. Praxel
    5. Taxol
    6. Taxol Konzentrat
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
450
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    The PFS comparison will be assessed at the second interim and final analyses using a logrank test stratified by country and residual disease status. Estimates for the letrozole/letrozole (L/L) vs paclitaxel/carboplatin/letrozole (CT/L) hazard ratio and its confidence interval will be obtained using a stratified Cox proportional hazards model. Potential confounding factors, including the stratification factors, performance status and self-declared racial designation will be considered in a final exploratory model. A forest plot of treatment hazard ratios with confidence intervals within subgroups will also be reported. PFS will be characterized by treatment group with Kaplan-Meier plots and estimates of the median PFS.
    measure
    Progression-free survival (PFS)
    time Frame
    Time from the randomized treatment assignment to documentation of disease progression (Response Evaluation Criteria in Solid Tumors 1.1) or death from any cause, whichever comes first, assessed up to 8 years
secondary Outcomes
  1. description
    The nature, frequency and degree of toxicity will be tabulated at the System Organ Class and AE Term levels using Common Terminology Criteria for Adverse Events version 5.0. Each patient will be represented according the maximum grade observed for each term, within randomized treatment assignment. Tabulations will show the number and percentage of patients by maximum grade, within their randomized treatment assignment.
    measure
    Incidence of adverse events (AE)
    time Frame
    Up to 8 years
  2. description
    Will be estimated as the binomial proportion of patients with best overall response of complete response (CR) or partial response (PR) among patients with measurable disease after cytoreductive surgery. Response rates and their 95% Wilson-Score confidence intervals will be estimated for each treatment arm, using the randomized treatment assignment. The odds-ratio for ORR in the L/L vs CT/L arms will be estimated from the multivariable logistic regression model adjusted for stratification factors.
    measure
    Objective response rate (ORR)
    time Frame
    Up to 8 years
  3. description
    Will be defined among patients with best overall response of CR or PR. Comparison of response duration between the randomized treatment arms will be supported by Kaplan Meier methods, and the corresponding estimates for median duration and its 95% confidence intervals.
    measure
    Duration of response
    time Frame
    Time from documentation of response under documentation of progression or death, which is observed first, assessed up to 8 years
  4. description
    Differences in OS across the randomized treatment groups will be assessed using Kaplan Meier methods, with median time to death estimates and the corresponding 95% confidence intervals. The L/L vs CT/L hazard ratio will be estimated by a proportional hazards model stratified by the randomization stratification factors.
    measure
    Overall survival (OS)
    time Frame
    Time between randomization and death from any cause, assessed up to 8 years
  5. description
    Will be quantified as the mean rate of adherence (MRA), calculated as the proportion of product not returned divided by the number of days since the previous visit at which study products were dispensed. Currently, the letrozole is delivered in a 2.5 mg pill, and the recommended dose is 2.5 mg per day. This outcome will be computed for each treatment cycle (generally 21 days). The mean MRA will be compared between the randomized treatment groups using linear mixed model methods. The model will be specified with a random patient effect, and fixed effects for randomized treatment indicator, time (cycle number) and the interaction, with an adjustment for the protocol stratification factors. Primary interest is in the difference in mean (MRA) at cycles 1, 6 and 12 between the treatment group. The results will be reported as the estimated mean (MRA) and 95% confidence intervals for each treatment/time combination. Treatment differences within stratification factors may also be considered.
    measure
    Adherence to letrozole maintenance therapy
    time Frame
    At cycles 1, 6, and 12
Full study description
brief Summary
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.
detailed Description
PRIMARY OBJECTIVE: I. To examine if letrozole monotherapy/maintenance (L/L) is non-inferior to intravenous (IV) paclitaxel/carboplatin and maintenance letrozole (CT/L) with respect to progression-free survival (PFS) in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction. SECONDARY OBJECTIVES: I. To compare the nature, frequency and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for each treatment arm. II. To compare the relative frequency of objective tumor response in those with measurable disease after cytoreductive surgery for each treatment arm. III. To compare overall survival for each treatment arm. IV. To compare the CT/L and L/L arms with respect to patients' adherence to letrozole therapy as measured by pill counts. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: 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 orally (PO) once daily (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. ARM II: 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. After completion of study treatment/intervention, patients/participants are followed up every 3 months for 1 year, then every 6 months for 3 years, then annually thereafter.
Source references
references
  1. citation
    Ilenkovan N, Ryan N, Roxburgh P, Bell S, Gourley C. Controversies in the management of serous borderline tumors and low-grade serous ovarian cancer. Int J Gynecol Cancer. 2025 Mar;35(3):101673. doi: 10.1016/j.ijgc.2025.101673. Epub 2025 Jan 30.
    pmid
    40058134
    type
    DERIVED
Source notices and limitations
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      source title
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      source update dates
      1. context
        Updated: May 14, 2025
        datetime
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        display
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    Preserved source evidence · Not medical advice