Genomic and Epigenomic Alterations After Cancer Treatment in Pregnancy

Cancer Clinical Trial

— GE-CIP  

Official title:

Genomic and Epigenomic Alterations After Cancer Treatment in Pregnancy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04125446
• Other study ID #: S62388
• Status: Recruiting
• Start date: October 15, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: September 2022
• Source: University Hospital, Gasthuisberg
• Contact: Ilana Struys
• Phone: +32 478734460
• Email: ilana.struys[@]uzleuven.be
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The investigators want to obtain a fundamental understanding if and which chemotherapeutic agents used for treating cancer during pregnancy are associated with placental and/or offspring (epi)genetic changes, potentially causing FGR and childhood/adult diseases later in life.

Description:

Rationale: Cancer is the second leading cause of death during the reproductive years and affects between 1:1000 and 2000 pregnant women. Previous studies from our group have shown that chemotherapeutic cancer treatment in pregnancy has reassuring outcomes in terms of cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care. However fetal growth restriction (FGR), which places an infant at significant risk of perinatal morbidity and mortality, is more common in women who were systemically treated during pregnancy compared to the non-cancer population. The possibility that chemotherapy during pregnancy causes placental (epi)genetic damage, and consequently induces FGR, or affects offspring DNA leading to potential deleterious effects later in life, such as cancer or other diseases, has not been investigated so far. As the cytotoxic effects of chemotherapy at DNA level have been well established, it could be speculated that chemotherapy-induced DNA damage may interfere with fetal and childhood health in the long term. The results of this study will lead to an increased understanding of potential toxic effects of chemotherapy for the unborn child and may therefore contribute to the development of safe and solid treatment regimens for pregnant cancer patients and their children. Objectives: To obtain a fundamental understanding if and which chemotherapeutic agents used for treating cancer during pregnancy are associated with offspring (epi)genetic changes, potentially causing FGR and childhood/adult diseases later in life. Study design: This international multicentre prospective observational trial functions as an extension of the CIP-study (Cancer in Pregnancy, S25470) and aims to collect cord blood, meconium and neonatal buccal cells at birth. Parental peripheral blood and buccal cells will be collected and used as reference. Minimal requirement to participate in this study is participation in Part I.IA of the original CIP-study. Through this CIP-study we are able to gather pregnancy-, malignancy- and placenta-related data. Study population: All patients with histological proven cancer during pregnancy and an ongoing pregnancy (≥24 weeks of gestation) treated with chemotherapy (alkylating agents, anthracyclines, taxanes and/or platinum derivates) or other treatment options (surgery, radiotherapy and/orsystemic treatment other than chemotherapy, or none). Main study parameters/endpoints: determination of potential (epi)genetic alterations in cord bloodand buccal cells of the newborn, and the association with chemotherapy concentrations measured in newborn tissue. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There are no risks associated nor benefits expected with participation in this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Cancer in pregnancy - CT-treated arm
• Histological proven cancer during pregnancy (any type and stage)
• (Former) participation in part I.IA of the CIP-study S25470 (and I.IB for the placental sub study)
• Treatment during pregnancy with one or a combination of the following

chemotherapeutic agents:

• Cyclophosphamide
• Anthracyclines
• Taxanes
• Platinum derivates
• Gestational age (GA) at birth =24 weeks Cancer in pregnancy - CT-untreated arm
• No treatment during pregnancy or surgery only (subgroup 1)
• Radiotherapy and/or systemic treatment (other than CT) during pregnancy (subgroup 2)
• GA at birth =24 weeks Healthy pregnant controls
• matched for maternal age, gestation at birth and infant gender with CT-treated arm
• GA at birth =24 weeks (only for placental study)

Exclusion Criteria:

• GA at birth <24 weeks (miscarriage or termination of pregnancy) (placental study)
• Mentally disabled women or patients who have a significantly altered mental status that would prohibit the understanding and giving of informed consent
• Any comorbidity that is associated with an enhanced risk of placental pathology or FGR such as hypertensive disorders, preeclampsia, (gestational) diabetes, SLE, Crohn's disease, renal or cardiac pathology (healthy pregnant controls)

Related Conditions & MeSH terms

• Cancer
• Pregnancy

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Gasthuisberg	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University Hospital, Antwerp, University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessing general genotoxicity of fetal DNA; genomic instability, de novo somatic mutations and methylation changes related to in utero exposure to chemotherapy	somatic mutations, structural alterations, methylation changes	through study completion, an average of 5 years
Secondary	Measuring concentration of chemotherapeutic drugs in offspring tissue (cord blood, meconium) in patients receiving cisplatin, carboplatin and/or cyclophosphamide treatment.	DNA adduct	through study completion, an average of 5 years