Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian or Primary Peritoneal Cancer
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|ClinicalTrials.gov Identifier: NCT04095364|
Recruitment Status : Recruiting
First Posted : September 19, 2019
Last Update Posted : November 13, 2019
|Condition or disease||Intervention/treatment||Phase|
|Low Grade Ovarian Serous Adenocarcinoma Primary Peritoneal Low Grade Serous Adenocarcinoma Stage II Ovarian Cancer AJCC v8 Stage IIA Ovarian Cancer AJCC v8 Stage IIB Ovarian Cancer AJCC v8 Stage III Ovarian Cancer AJCC v8 Stage IIIA Ovarian Cancer AJCC v8 Stage IIIA1 Ovarian Cancer AJCC v8 Stage IIIA2 Ovarian Cancer AJCC v8 Stage IIIB Ovarian Cancer AJCC v8 Stage IIIC Ovarian Cancer AJCC v8 Stage IV Ovarian Cancer AJCC v8 Stage IVA Ovarian Cancer AJCC v8 Stage IVB Ovarian Cancer AJCC v8||Drug: Carboplatin Drug: Letrozole Drug: Paclitaxel||Phase 3|
I. To examine if letrozole monotherapy/maintenance is non-inferior to intravenous (IV) paclitaxel/carboplatin and maintenance letrozole 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.
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 paclitaxel + carboplatin/letrozole (CT/L) and letrozole monotherapy (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.
ARM II: Patients receive letrozole PO QD in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, then annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||450 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase III, Two-Arm Trial of Paclitaxel/Carboplatin/Maintenance Letrozole Versus Letrozole Monotherapy in Patients With Stage II-IV, Primary Low-Grade Serous Carcinoma of the Ovary or Peritoneum|
|Actual Study Start Date :||August 26, 2019|
|Estimated Primary Completion Date :||February 1, 2027|
|Estimated Study Completion Date :||February 1, 2027|
Experimental: Arm I (paclitaxel, carboplatin, letrozole)
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.
Experimental: Arm II (letrozole)
Patients receive letrozole PO QD in the absence of disease progression or unacceptable toxicity.
- 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 ]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.
- Incidence of adverse events (AE) [ Time Frame: Up to 8 years ]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.
- Objective response rate (ORR) [ Time Frame: Up to 8 years ]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.
- 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 ]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.
- Overall survival (OS) [ Time Frame: Time between randomization and death from any cause, assessed up to 8 years ]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.
- Adherence to letrozole maintenance therapy [ Time Frame: At cycles 1, 6, and 12 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04095364
|Principal Investigator:||Amanda N Fader||NRG Oncology|