Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.

Autologous Heterotopic Fresh Ovarian Graft in Young Woman With Locally Advanced Cervical Cancer Eligible for Pelvic Radiotherapy Treatment

Pelvic chemoradiotherapy (CRT) is an effective treatment for Locally Advanced Cervical Cancer (LACC). However, CRT induces premature ovarian failure ceasing the production of ovarian hormones. This may lead to severe consequences to the patient's life quality, sexuality and overall healthy. An acceptable treatment to minimize the adverse effects caused by the lack of ovarian hormones is hormonal replacement but less than 40% of the patients younger than 50 years have access to this treatment. A second alternative treatment is ovarian transposing which is a surgical technique with variable success rate depending on how far the ovaries are from the radiotherapy field. A third, more promising, alternative is involves using autologous ovarian tissue as a graft in tissues far from the radiotherapy field. This treatment has the potential of maintaining the natural ovarian hormones production at a lower-cost and requiring a simpler procedure. The primary objective of this randomized phase 1-2 clinical trial is to validate the feasibility of ovarian tissue engraft into fatty tissue and its endocrine functionality.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Cervical Carcinoma; Premature Ovarian Failure
• Intervention / Treatment: Procedure: Ovarian graft

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Marilia Bertolazzi, MD; Phone Number: 5519989172189; Email: marilia.bertolazzi@hc.fm.usp.br
• Study Contact Backup: Name: Jesus Carvalho; Email: jesus.carvalho@hc.fm.usp.br

Study Locations

• Brazil
  • São Paulo, Brazil, 01246-000
    • Recruiting
    • Instituto do Cancer do Estado de Sao Paulo
    • Contact: Elaine Longo; Phone Number: 55 11 38932632; Email: elaine.longo@hc.fm.usp.br
    • Contact: Marilia Bertolazzi, PHD; Phone Number: 5519989172189; Email: marilia.bertolazzi@hc.fm.usp.br
    • Principal Investigator: Jesus Carvalho, PHD
    • Sub-Investigator: Marilia Bertolazzi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologic diagnosis of squamous cell carcinoma or adenocarcinoma of the cervix.
• FIGO 2018 staging IB3 to IVA.
• Absence of ovarian involvement.
• Age ≤35 Years.
• Absence of metastatic disease.
• Written consent.

Exclusion Criteria:

• Previous treatment for cervical cancer or other malignant diseases.
• Rare histology tumors.
• Absence of one or both ovaries.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard treatment; 10 patients: Pelvic Chemoradiotherapy
Experimental: Ovarian Graft; 10 patients: Before the beginning of pelvic radiotherapy, one of the ovaries will be removed by laparoscopy. Ovary slices of 1-2 mm will be prepared in sterile environment and engrafted in the fatty tissue of inner tight. One representative fragment will undergo histologic evaluation. These procedures will be done in the same surgical time.	Procedure: Ovarian graft; Before the beginning of pelvic radiotherapy, one of the ovaries will be removed by laparoscopy. Ovary slices of 1-2 mm will be prepared in sterile environment and engrafted in the fatty tissue of inner tight. One representative fragment will undergo histologic evaluation. These procedures will be done in the same surgical time.; Other Names: Autologous Heterotopic Fresh Ovarian Graft

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosage of serum levels of follicle stimulating hormone (FSH) in mUI/ml in intervention (engraft of ovarian tissue into fatty tissue) and control groups. Dosage will be performed at baseline and post radiotherapy (2, 6, 12 and 24 months).	Endocrine functionality is defined as FSH levels under 25 mUI/ml.	2 years
Dosage of serum levels of estradiol in pg/ml in intervention (engraft of ovarian tissue into fatty tissue) and control groups. . Dosage will be performed at baseline and post radiotherapy (2, 6, 12 and 24 months).	Endocrine functionality is defined as estradiol upper 47 pg/mL.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosage of serum levels of glucose in mg/dL in intervention and control groups. (Time frame: At baseline and post radiotherapy month 2, 6, 12 and 24).	Evaluation of glucose metabolism.	2 years
Measure of serum glycated hemoglobin in percentage in intervention and control groups. (Time frame: At baseline and post radiotherapy month 2, 6, 12 and 24).	Evaluation of glucose metabolism.	2 years
Measure of serum levels of cholesterol in mg/dL in intervention and control groups. (Time frame: At baseline and post radiotherapy month 2, 6, 12 and 24).	Evaluation of lipid metabolism.	2 years
Measure of serum levels of triglycerides in mg/dL in intervention and control groups. (Time frame: At baseline and post radiotherapy month 2, 6, 12 and 24).	Evaluation of lipid metabolism.	2 years
Evaluate the changes in bone mineral density (BMD) in femoral neck and lumbar spine by bone densitometry, evaluating T and Z scores standard deviation (SD) in intervention and control groups. Time frame: At baseline and post radiotherapy month 12 and 24.		2 years
Bioimpedance monitoring to evaluate changes in body composition by fat and lean mass percentage in intervention and control groups. Time frame: At baseline and post radiotherapy month 12 and 24).		2 years
Quantification of body mass index reported in kg/m2 in intervention and control groups. Time frame: At baseline and post radiotherapy month 12 and 24).	Evaluation of changes in body mass.	2 years
Score life quality in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) in intervention and control groups.	EORTC QLQ C30 was developed and validated to assess the quality of life of cancer patients. The 30-item EORTC QLQ-C30 is a disease-specific measure that assesses multiple QoL domains in patients with cancer. There are five functioning scales that measure physical, role, emotional, cognitive, and social functioning. Three symptom scales measure fatigue, pain, and nausea/vomiting.	2 years
Score life quality in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Cervical Cancer Module (EORTC QLQ C30 CX24) in intervention and control groups.	EORTC QLQ-CX24 Scoring Manual The Cervical Cancer Module is a supplementary questionnaire module to be employed in conjunction with the QLQ-C30. The EORTC QLQ-CX24 was designed to assess disease-specific and treatment-specific aspects of QoL in patients with cervical cancer.	2 years

Collaborators and Investigators

• Sponsor: MARILIA ALBANEZI BERTOLAZZI

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): June 8, 2024

Study Registration Dates

• First Submitted: June 9, 2022
• First Submitted That Met QC Criteria: July 13, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Primary Ovarian Insufficiency; Menopause, Premature
• Other Study ID Numbers: NP1782

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No