Genomic and Epigenomic Alterations After Cancer Treatment in Pregnancy (GE-CIP)

• ClinicalTrials.gov Identifier: NCT04125446
• Recruitment Status: Recruiting
• First Posted: October 14, 2019
• Last Update Posted: September 27, 2022
• Sponsor: University Hospital, Gasthuisberg
• Collaborators: University Hospital, Antwerp; University Hospital, Ghent; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Information provided by (Responsible Party): Frederic Amant, University Hospital, Gasthuisberg

Study Description

Brief 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.

Condition or disease
Cancer; Pregnancy

Detailed 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.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 150 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 9 Months
• Official Title: Genomic and Epigenomic Alterations After Cancer Treatment in Pregnancy
• Actual Study Start Date: October 15, 2019
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Groups and Cohorts

Group/Cohort
Cancer in pregnancy chemo treated; Patients that received at least one of the following treatments: Carboplatin, Cisplatin, Cyclophosphamide, Paclitaxel and/or anthracyclines, the latter being the most given type of CT during pregnancy
Cancer in Pregnancy not chemo treated; Women who were not treated with CT during pregnancy, including those who were solely surgically treated or did not receive any treatment during pregnancy, will be included in the CT-unexposed control arm
healthy pregnancies; A group of healthy pregnant women without cancer will form the second control group

Outcome Measures

Primary Outcome Measures :

1. Assessing general genotoxicity of fetal DNA; genomic instability, de novo somatic mutations and methylation changes related to in utero exposure to chemotherapy [ Time Frame: through study completion, an average of 5 years ]
   somatic mutations, structural alterations, methylation changes

Secondary Outcome Measures :

1. Measuring concentration of chemotherapeutic drugs in offspring tissue (cord blood, meconium) in patients receiving cisplatin, carboplatin and/or cyclophosphamide treatment. [ Time Frame: through study completion, an average of 5 years ]
   DNA adduct

Biospecimen Retention:   Samples With DNA

Parental blood, cord blood, meconium, buccal swabs

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

The current study will focus on patients that received at least one of the following treatments: carboplatin, cisplatin, cyclophosphamide, paclitaxel and/or anthracyclines, the latter being the most given type of CT during pregnancy (cfr. also Table 1). Women who were not treated with CT during pregnancy, including those who were solely surgically treated or did not receive any treatment during pregnancy, will be included in the CT-unexposed control arm.In the CT-unexposed arm, we will also include women that had systemic treatment other than chemotherapy (e.g. targeted therapies) and/or radiotherapy. A group of healthy pregnant women without cancer, delivering in our participating centres, will form the second control group.

Criteria

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)

Contacts and Locations

Contacts

Contact: Ilana Struys; +32 478734460; ilana.struys@uzleuven.be

Contact: Liesbeth Lenaerts, PhD,Ir; +32 16 344468; liesbeth.lenaerts@kuleuven.be

Locations

Belgium

University Hospitals Leuven; Recruiting

Leuven, Belgium, 3000

Contact: Frédéric Amant, MD,PhD +32 16 344252 frederic.amant@uzleuven.be

Contact: Kristel Van Calsteren, MD,PhD +32 16 346192 kristel.vancalsteren@uzleuven.be

Sub-Investigator: Bernard Thienpont, PhD,Ir

Sub-Investigator: Lode Godderis, MD,PhD

Sub-Investigator: Thierry Voet, PhD,Ir

Sponsors and Collaborators

University Hospital, Gasthuisberg

University Hospital, Antwerp

University Hospital, Ghent

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

• Principal Investigator: Frédéric Amant, MD,PhD; Universitaire Ziekenhuizen KU Leuven

More Information

• Responsible Party: Frederic Amant, Clinical Professor, Principal Investigator, University Hospital, Gasthuisberg
• ClinicalTrials.gov Identifier: NCT04125446
• Other Study ID Numbers: S62388
• First Posted: October 14, 2019
• Last Update Posted: September 27, 2022
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Frederic Amant, University Hospital, Gasthuisberg:

cancer in pregnancy; chemotherapy; offspring; genotoxicity