Effects of Oncological Treatment During Pregnancy on Mother and Child

Official title

Oncological Treatment During Pregnancy: Pharmacokinetics of Chemotherapy and Long Term Follow up of the Offspring

Overview

The researchers aim to investigate the outcome (overall survival) of mothers who are diagnosed and/or treated for cancer during pregnancy. Furthermore they want to test the hypothesis that children who were exposed to cancer or cancer treatment (cytotoxic drugs, radiation therapy, targeted therapy,...) develop normally (neurologic and cardiologic examination).

Detailed description

Study contains several study parts (protocol version 4.4):

\*\*\*\*\*\*\*\*\*\*Part I. Pregnancy, delivery and maternal health\*\*\*\*\*\*\*\*\*\* Part I.I.A. Registration study 'Cancer during pregnancy' mother and neonate None Part I.I.B. Effects of prenatal exposure to cancer treatment on fetal growth. The association between placental pathophysiologic mechanisms (histopathology and immunohistochemistry), circulating maternal factors and fetal growth.

From participating women, a maternal blood sample will be collected during or shortly after birth. Also, an umbilical cord blood sample and placental and umbilical cord biopsies will be drawn.

Part I.II. Measurement of maternal and paternal anxiety and emotional needs when confronted with a cancer diagnosis during pregnancy The participants will be asked to complete questionnaires.

\*\*\*\*\*\*\*\*\*\*Part II. Child\*\*\*\*\*\*\*\*\*\* Long term follow up of children and adolescents in utero exposed to chemotherapy and/or radiotherapy Regular check-ups of the child, at the age of 6 months, 18 months, 3y, 6y, 9y, 12y, 15y, and 18y, and after the age of 18 years: 5-yearly cardiologic assessment and questionnaires (23y, 28y, 33y, 38y, and 43y). Optional at the ages of 9y, 12y, 15y and 18y: MRI session.

Summary part I:

Prospectively the outcome of mothers diagnosed and/or treated for cancer during pregnancy will be registered and investigated.

Summary Part II:

In a prospective trial we invite children that were exposed to cytotoxic drugs or radiotherapy in utero for a standardized neurological and cardiological examination. The examinations will be done by qualified psychologists, neurological and cardiological pediatricians.

Primary outcome measures

• Follow-up of the mothers diagnosed with cancer during pregnancy [Time frame: anticipated]
• Follow-up of the children antenatally exposed to chemotherapy or radiotherapy [Time frame: anticipated]

Eligibility criteria

Patients do not need to participate in both; however, preferentially both study parts should be performed.

\*\*\*\*\*\*\*\*\*\*\*\*\*\*Part I: Pregnancy, delivery and maternal health\*\*\*\*\*\*\*\*\*\*\*\*\*\*

Patients must meet the following inclusion criteria:

• Histologically proven cancer in association with a pregnancy (during pregnancy or cancer dagnosis within 5 years after pregnancy)
• > 18 years of age, premenopausal
• Patients who have given their signed and written informed consent to participate in the trial after fully understanding the implication of the protocol
• Women receiving any cytotoxic drug or radiation therapy during pregnancy are allowed for the assessment of the maternal and fetal outcome (Part II).

Exclusion criteria

• Mentally disabled or significantly altered mental status that would prohibit the understanding and giving of informed consent

\*\*\*\*\*\*\*\*\*\*\*\*\*\*Part II: Follow-up of children\*\*\*\*\*\*\*\*\*\*\*\*\*\*

Inclusion criteria

\- Children that were prenatally exposed to cancer of cancer treament. Informed Consent is asked from parents. From the age of 12 years, informed assent is additionally asked from the child. After the age of 18 years, informed consent is solely asked of the offspring.

Exclusion criteria

• Mentally disabled or significantly altered mental status that would prohibit the understanding and giving of informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Italy · 5 centers

• European Institute of Oncology (2010-ongoing) — Milan
• Fondazione IRCCS Ca'Granda Ospedale Maggiore (2012-ongoing) — Milan
• Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico Milano (2017-ongoing) — Milan
• San Raffaele Hospital (2017-ongoing) — Milan
• CIttà della Salute e della Scienza di Torino (2015-ongoing) — Torino

Greece · 4 centers

• Euroclinic Hospital (2016-ongoing) — Athens
• Hellenic Anticancer-Oncological Hospital of Athens (retrospective 2015-2018) — Athens
• Ioannina University Hospital (retrosepctive 2015-2018) — Ioannina
• Hippokration Hospital (retrospective 2015-2018) — Thessaloniki

Poland · 3 centers

• Medyczne Macierzynstwo (retrospective 2010-2018) — Krakow
• University Hospital Krakow (2018-ongoing) — Krakow
• Pozanan University of Medical Sciences (2017-ongoing) — Poznan

Russia · 3 centers

• N.N.Blokchin National Medical Research Center of Oncology (2013-2018 retrospective; 2018-o — Moscow
• Research Center for Obstetrics, Gynecology and Perinatology (2014-ongoing) — Moscow
• Almazov National Medical Research Center (2018-ongoing) — Saint Petersburg

Belgium · 2 centers

• UCL Brussels (2013-ongoing) — Brussels
• UZ Gasthuisberg, Katholieke Universiteit Leuven (2004-ongoing) — Leuven

Czechia · 2 centers

• University Hospital Ostrava (2018-ongoing) — Ostrava
• 3rd medical faculty of Charles University (2010-ongoing) — Prague

United States · 1 center

• Cooper University Hospital (2015-ongoing) — Camden

Argentina · 1 center

• Instituto Alexander Fleming — Buenos Aires

Austria · 1 center

• Universitätsklinik für Frauenheilkunde und Geburtshilfe (retrospective 2016-2018) — Graz

Denmark · 1 center

• Copenhagen University Hospital (2015-ongoing) — Copenhagen

France · 1 center

• Hopital Bichat-Claude-Bernard (retrospective until 2018) — Paris

Germany · 1 center

• Universitätsklinik Freiburg (retrospective until 2018) — Freiburg im Breisgau

Mexico · 1 center

• Regional Hospital of High Specialty of Ixtapaluca (2018-ongoing) — Ixtapaluca

Netherlands · 1 center

• Erasmus Medical Center (2014-ongoing) — Rotterdam

Norway · 1 center

• Haukeland University Hospital (2017-ongoing) — Bergen

Portugal · 1 center

• Hospital de Vila Franca de Xira (2017-ongoing) — Vila Franca de Xira

Sweden · 1 center

• Karolinska University Hospital (2017-ongoing) — Stockholm

Tunisia · 1 center

• F.Hached University Teaching Hospital (retrospective 2016-2018) — Sousse

Turkey (Türkiye) · 1 center

• Trakya University Faculty of Medicine (retrospective 2015-2018) — Edirne

Ukraine · 1 center

• Grigoriev Institute for medical Radiology (retrospective until 2018) — Kharkiv

Publications

• Caluwaerts S, VAN Calsteren K, Mertens L, Lagae L, Moerman P, Hanssens M, Wuyts K, Vergote I, Amant F. Neoadjuvant chemotherapy followed by radical hysterectomy for invasive cervical cancer diagnosed during pregnancy: report of a case and review of the literature. Int J Gynecol Cancer. 2006 Mar-Apr;16(2):905-8. doi: 10.1111/j.1525-1438.2006.00223.x. PMID 16681782
• Van Calsteren K, Berteloot P, Hanssens M, Vergote I, Amant F, Ganame J, Claus P, Mertens L, Lagae L, Delforge M, Paridaens R, Noens L, Humblet Y, Vandermeersch B, De Muylder X. In utero exposure to chemotherapy: effect on cardiac and neurologic outcome. J Clin Oncol. 2006 Apr 20;24(12):e16-7. doi: 10.1200/JCO.2006.06.1382. No abstract available. PMID 16622256
• Lishner M, Avivi I, Apperley JF, Dierickx D, Evens AM, Fumagalli M, Nulman I, Oduncu FS, Peccatori FA, Robinson S, Van Calsteren K, Vandenbroucke T, Van den Heuvel F, Amant F. Hematologic Malignancies in Pregnancy: Management Guidelines From an International Consensus Meeting. J Clin Oncol. 2016 Feb 10;34(5):501-8. doi: 10.1200/JCO.2015.62.4445. Epub 2015 Nov 30. PMID 26628463
• Amant F, Verheecke M, Wlodarska I, Dehaspe L, Brady P, Brison N, Van Den Bogaert K, Dierickx D, Vandecaveye V, Tousseyn T, Moerman P, Vanderstichele A, Vergote I, Neven P, Berteloot P, Putseys K, Danneels L, Vandenberghe P, Legius E, Vermeesch JR. Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing. JAMA Oncol. 2015 Sep;1(6):814-9. doi: 10.1001/jamaoncol. PMID 26355862
• de Haan J, Verheecke M, Amant F. Management of ovarian cysts and cancer in pregnancy. Facts Views Vis Obgyn. 2015;7(1):25-31. PMID 25897369
• Amant F, Han SN, Gziri MM, Vandenbroucke T, Verheecke M, Van Calsteren K. Management of cancer in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2015 Jul;29(5):741-53. doi: 10.1016/j.bpobgyn.2015.02.006. Epub 2015 Mar 4. PMID 25797199
• van Dam L, Han SN, Dierickx D, Amant F. Optimal staging of lymphoma during pregnancy is crucial. Womens Health (Lond). 2015 Mar;11(2):101-2. doi: 10.2217/whe.14.77. No abstract available. PMID 25776282
• Han SN, Van Peer S, Peccatori F, Gziri MM, Amant F; International Network on Cancer, Infertility and Pregnancy. Contraception is as important as fertility preservation in young women with cancer. Lancet. 2015 Feb 7;385(9967):508. doi: 10.1016/S0140-6736(15)60201-X. No abstract available. PMID 25705843

Identifiers

NCT: NCT00330447 · cancer in pregnancy

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗