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Trial record 1 of 1 for:    NRG-GY019
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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
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

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 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 or peritoneum compared to paclitaxel and carboplatin without letrozole.

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

Detailed Description:

PRIMARY OBJECTIVES:

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.

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Experimental: Arm II (letrozole)
Patients receive letrozole PO QD in the absence of disease progression or unacceptable toxicity.
Drug: Letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up
  • All women will, by definition, be considered menopausal due to surgical removal of both ovaries prior to trial enrollment
  • Patients must have newly diagnosed, stage II-IV low-grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinoma) of the ovary or peritoneum. Tumors must be assessed for nuclear p53 staining
  • Appropriate stage for study entry based on the following diagnostic workup:

    • History/physical examination within 14 days prior to registration
    • Contrast-enhanced imaging of the chest, abdomen and pelvis within 28 days prior to registration
  • 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 prior to initial 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)
  • Patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible if there is no hydronephrosis and the estimated creatinine clearance (CCr) is >= 30 ml/min (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)
  • Alkaline phosphatase less than or equal to 2.5 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

Exclusion Criteria:

  • Patients with concomitant invasive malignancy or a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the past five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol
  • Patients may not have received neoadjuvant 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 or uncontrolled systemic infection
  • Patients with >= grade 2 baseline neuropathy
  • Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive

Information from the National Library of Medicine

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


Locations
Show Show 280 study locations
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Amanda N Fader NRG Oncology
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Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT04095364    
Other Study ID Numbers: NRG-GY019
NCI-2019-01460 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY019 ( Other Identifier: NRG Oncology )
NRG-GY019 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: September 19, 2019    Key Record Dates
Last Update Posted: November 13, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Paclitaxel
Carboplatin
Albumin-Bound Paclitaxel
Letrozole
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Aromatase Inhibitors
Steroid Synthesis Inhibitors