Efficacy of Letrozole in Recurrent Ovarian Cancer (MITO32)

June 4, 2020 updated by: Claudia Marchetti, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

PHASE III RANDOMIZED CONTROL CASE STUDY OF LETROZOLE IN WOMEN WITH HEAVILY PRETREATED OVARIAN CANCER (MITO 32)

Randomized phase III multicenter study investigating the role of letrozole in heavily pretreated recurrent ovarian cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, open-label, phase III, multicenter, global study evaluating the efficacy and safety of Letrozole in heavily pretreated recurrent ovarian cancer patients in comparison to physician' choice chemotherapy.

Subjects who meet all the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 ratio to one of the two arms, as follow:

Arm A: Letrozole 1 tablet (2,5 mg) orally once a day in 28-day cycles Arm B: Pegylated Liposomal Doxorubicin 40 mg/m2 d1q28 or Topotecan 4 mg/m2 d1,8,15q28 or Gemcitabine 1000 mg/m2 d1,8,15q28 or Paclitaxel 80 mg/m2 d1,8,15q28 In case of objective response and acceptable toxicity, no maximum number of cycles of treatment is defined.

The aim of the study is to assess the activity of Letrozole in women with recurrent epithelial ovarian cancer, heavily pretreated.

Study Type

Interventional

Enrollment (Anticipated)

236

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Female of 18 years of age or older
  • Histologically or cytologically documented invasive epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer
  • Platinum resistant or refractory disease (patients who did not respond to last platinumbased therapy or with last relapse occurred < 6 months from the last dose of platinum) or patients not amenable of platinum treatment
  • >3 previous chemotherapy lines
  • ECOG performance status 0 -2
  • Measurable and evaluable disease according to RECIST criteria confirmed by radiological imaging: at least one lesion of ≥ 1.0 cm for non-lymph nodes or ≥ 1.5 cm in short-axis diameter for lymph nodes at CT scan (Subjects with isolated rising CA-125 without radiologically visible disease are excluded)
  • Left Ventricular Ejection Fraction (LVEF) ≥ institutional lower limit normal
  • Estimated life expectancy ≥ 16 weeks

  • Adequate functions evidenced by:

    • Hemoglobin ³10.0 g/dl
    • Absolute neutrophil count ³1.5 x 109/L
    • White blood cells >3x109/L
    • Platelet >100 x109/L
    • AST and ALT £ 2.5 x Upper limit of normal, unless liver metastasis, in which case AST and ALT < or = 5 x Upper limit of normal will be accepted
    • Bilirubin ≤ 1.5 times the upper limit of normal (ULN)
    • Estimated glomerular filtration ³ 60mL/min using the Cockcroft-Gault equation.
  • Patient able to comply with the treatment
  • Evidence of not pregnancy status as documented by a negative beta-human chorionic gonadotropin (ß-hCG) test
  • Not breastfeeding women
  • Patients with child-bearing potential using (or willing to use) effective contraception during treatment and 3 months ahead unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically.
  • Comprehension and signature of the informed consent

Exclusion Criteria:

  • Subjects with borderline ovarian cancer
  • Subject with low malignant potential tumors
  • Less than 3 lines of previous therapies
  • Platinum sensitive disease (last relapse occurred > 6 months from the last dose of platinum)
  • Less than 4 weeks from last dose of therapy with any investigational agent, or chemotherapy
  • History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 3 years or longer
  • Breastfeeding women
  • Pregnant women
  • Prior therapy with letrozole.
  • Severe osteoporosis documented by BMD (Bone Mineral Density) T-score ≤ -2.5 with existing fragility fracture(s)
  • Patients with a known hypersensitivity to Paclitaxel , PLD, Topotecan, Gemcitabine or Letrozole or any case of severe toxicity related to them. Also Patients with a known hypersensitivity to any of the ingredients or excipients of the IMPs (e.g. macrogolglycerol ricinoleate (polyoxyl castor oil), ethanol, anhydrous, citric acid, anhydrous, sodium chloride hydrochloric acid, mannitol, sodium acetate, sodium hydroxide, tartaric acid, lactose monohydrate, maize starch, hypromellose Type 2910, cellulose microcrystalline, sodium starch glycolate type A, colloidal anhydrous silica, magnesium stearate, hypromellose 6 cp E464, titanium dioxide E171, Iron oxide yellow E172, Macrogol 400, talc E553b)
  • Prior resistance to Paclitaxel, PLD, Topotecan, Gemcitabine
  • Patients with active hepatic disease (HCV or HBV infections), hepatic severe impairment or cirrhosis
  • Bowel obstruction, sub-occlusive disease, prior gastrectomy, symptomatic brain metastases.
  • Myocardial infarct within six months before enrolment , NYHA Class II or worse heart failure, unstable angina, serious cardiac arrhythmia or cardiac arrhythmia requiring treatment.
  • Any serious concomitant illness requiring treatment
  • Pre-existing peripheral neuropathy > CTCAE Grade 2.
  • Concomitant use of strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, voriconazole, ritonavir, clarithromycin, and telithromycin) or strong CYP2A6 inhibitors (e.g. methoxsalen) because they may increase exposure to letrozole.
  • Concomitant use of inducers of CYP3A4 (e.g. phenytoin, rifampicin, carbamazepine, phenobarbital, and St. John's Wort) which may reduce exposure to letrozole.
  • Concomitant use of medicinal products with a narrow therapeutic index that are substrates for CYP2C19 (e.g. phenytoin, clopidrogel) that may have their systemic serum concentrations altered by letrozole.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Letrozole
Letrozole 1 tablet (2,5 mg) orally once a day
Drug: Letrozole 2.5mg
This study will investigate the role of Letrozole in patients affected by heavily pretreated platinum resistant ovarian cancer, compared to standard treatment.
Active Comparator: Standard Chemotherapy
Either Paclitaxel 80 mg/m2 as a 1-h infusion, on days 1,8,15,22 every 28 days or Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 given every 4 weeks or Topotecan 4mg/m2 IV on days 1,8,15 every 4 weeks or Gemcitabine 1000 mg/m2 IV over 30 min on days 1,8,15 every 28 days.
Drug: Standard single agent chemotherapy
Either Paclitaxel 80 mg/m2 as a 1-h infusion, on days 1,8,15,22 every 28 days or Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 given every 4 weeks or Topotecan 4mg/m2 IV on days 1,8,15 every 4 weeks or Gemcitabine 1000 mg/m2 IV over 30 min on days 1,8,15 every 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patient alive at 12 months
Time Frame: 30 months
Evaluate the difference in terms of proportion of survivals at 12 months between the two arms.
30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: 30 months
Progression Free Survival
30 months
OS
Time Frame: 30 months
Overall Survival
30 months
ORR
Time Frame: 30 months
Objective Response Rate (according to RECIST criteria version 1.1)
30 months
TPST
Time Frame: 30 months
Time from randomization to the start of the primary subsequent therapy
30 months
TSST
Time Frame: 30 months
Time from randomization to the start of the secondary subsequent therapy
30 months
Toxicity profile evaluated according to NCI-CTCAE version 5.0
Time Frame: 30 months
Toxicity profile (evaluated according to NCI-CTCAE version 5.0)
30 months
QoL
Time Frame: 30 months
Quality of Life (evaluated by EORTC QLQ-C30/ QLQ-OV28 questionnaire)
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2020

Primary Completion (Anticipated)

December 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

May 15, 2020

First Submitted That Met QC Criteria

June 4, 2020

First Posted (Actual)

June 9, 2020

Study Record Updates

Last Update Posted (Actual)

June 9, 2020

Last Update Submitted That Met QC Criteria

June 4, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MITO32

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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