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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cancer Trials Ireland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Jan 2025 → ongoing

Decision date (initial)

2024-09-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Irish Cancer Society and Friends of Cancer Trials Ireland

External identifiers

EU CT number

2024-516530-36-00

EudraCT number

2022-002877-27

ClinicalTrials.gov

NCT04095364

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Therapy, Safety

To examine if letrozole monotherapy/maintenance (L/L) is noninferior to IV paclitaxel/carboplatin and maintenance letrozole (CT/L) with respect to PFS in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction

Secondary objectives 4

1. To compare the nature, frequency and maximum degree of toxicity as assessed by CTCAE v5.0 for each treatment arm.
2. To compare the relative frequency of objective tumour response in those with measurable disease after cytoreductive surgery for each treatment arm.
3. To compare overall survival for each treatment arm.
4. To compare the CT\L and L\L arms with respect to patients adherence to letrozole therapy as measured by pill counts.

Conditions and MedDRA coding

low-grade serous carcinoma of the ovary or peritoneum

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
2. 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). If aberrant p53 expression is found on p53 IHC, the patient is NOT eligible (e.g., aberrant p53 expression is consistent with mutant TP53 and supports a diagnosis of high grade serous ovarian cancer).
3. Appropriate stage for study entry based on the following diagnostic workup: o History/physical examination within 14 days prior to registration; o Contrast-enhanced imaging of the chest, abdomen and pelvis within 28 days prior to registration.
4. Age ≥ 18
5. Patients must have undergone an attempt at maximal upfront cytoreductive surgery, with either optimal (<=1cm diameter residual disease/nodule) or suboptimal residual disease (>1 cm diameter residual disease/nodule) status allowed.
6. Patients must have undergone a bilateral salpingo-oophorectomy
7. Patients must have an ECOG Performance Status of 0, 1 or 2 within 14 days prior to registration (protocol Appendix I).
8. Patients must be within ≤8 weeks of primary cytoreductive surgery at time of randomization.
9. Patients must be able to take per oral (P.O.) medications.
10. Patients must have adequate organ and marrow function as defined below: - Bone marrow function within 14 days prior to registration defined as follows: o Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl o Platelets greater than or equal to 100,000 cells/mcl - Adequate renal function within 14 days prior to registration defined as follows: o Creatinine less than or equal to 1.5 x ULN -Adequate hepatic function within 14 days prior to registration defined as follows: o Bilirubin less than or equal to 1.5 x ULN o ALT and AST less than or equal to 3 x ULN
11. The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
12. 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 9

1. Patients with any of the following conditions are NOT eligible for this study.
2. Patients may not have received neoadjuvant or adjuvant chemotherapy or radiotherapy for the treatment of this disease.
3. Patients with known hypersensitivity to letrozole or hypersensitivity/intolerance to carboplatin/paclitaxel therapy.
4. 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 (protocol Appendix II).
5. Patients with known central nervous system metastases
6. Patients with active (except for uncomplicated urinary tract infection) or uncontrolled systemic infection.
7. Patients with ≥grade 2 baseline neuropathy
8. Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
9. Patients may not have received previous hormonal therapy for the treatment of this disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. The primary efficacy endpoint is Progression Free Survival (PFS). PFS is defined as the time (in months) from the randomized treatment assignment to documentation of disease progression (RECIST 1.1) or death from any cause, whichever comes first.
2. The study includes two interim analyses. At 20% information time, a futility analysis will be conducted. At 40% information time, both efficacy and futility will be assessed. The PFS comparison will be assessed at the second interim and final analyses using a logrank test stratified by country and residual disease status.
3. Full analysis will be performed after the date on which the last participant was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events.

Secondary endpoints 6

1. Toxicity
2. Objective Tumour Response
3. Overall Survival
4. Adherence to Letrozole Maintenance Therapy
5. The study includes two interim analyses. At 20% information time, a futility analysis will be conducted. At 40% information time, both efficacy and futility will be assessed.
6. Full analysis will be performed after the date on which the last participant was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cancer Trials Ireland

Sponsor organisation

Cancer Trials Ireland

Address

Rcsi House, 121 Saint Stephen's Green 121 Saint Stephen's Green

City

Dublin 2

Postcode

D02 H903

Country

Ireland

Scientific contact point

Organisation

Cancer Trials Ireland

Contact name

Head of Operations

Public contact point

Organisation

Cancer Trials Ireland

Contact name

Head of Operations

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications