FIGO 2018 stage IB2 (>2 cm - ≤4 cm ) Cervical Cancer Treated with Neoadjuvant Chemotherapy Followed by Fertility Sparing Surgery (CoNteSSa) / Neo-Adjuvant Chemotherapy and Conservative Surgery in Cervical Cancer to Preserve Fertility (NeoCon-F)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Health Network, Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Feb 2021 → ongoing

Decision date (initial)

2024-07-12

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-507230-24-00

EudraCT number

2020-000404-11

ClinicalTrials.gov

NCT04016389

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To assess the feasibility of preserving fertility in women with node negative, 2018 FIGO stage IB2 cervical cancer with lesions measuring >2 cm - ≤4 cm by administering neo-adjuvant chemotherapy
(NACT) followed by fertility sparing surgery (FSS) and no adjuvant therapy

Secondary objectives 6

1. To evaluate the safety of NACT in women with node negative, 2018 FIGO stage IB2 cervical cancer with lesions measuring >2 cm - ≤4 cm assessed as toxicities of NACT by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and the rate of completion of NACT
2. To evaluate the response rate based on RECIST 1.1 following neoadjuvant chemotherapy for patients with node negative stage FIGO 2018 IB2 cervical cancer
3. To assess the rate of FSS
4. To evaluate the surgical complication rate following FSS by the Clavien-Dindo classification of surgical morbidity
5. To evaluate the safety of the fertility sparing surgery (FSS) in women with node negative, FIGO 2018 stage IB2 cervical cancer measuring >2 cm - ≤4 cm measured as two and three-year recurrence free survival
6. To evaluate overall survival (OS) up to two and three years for patients who undergo neoadjuvant chemotherapy followed by fertility sparing surgery.

Conditions and MedDRA coding

Cervical cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Eligibility Criteria for Neoadjuvant Chemotherapy: Patients must have histologically confirmed invasive cervical cancer with adenocarcinoma, adenosquamous or squamous histology and FIGO 2018 IB2 measuring >2 cm - ≤4 cm by radiological imaging (T2 sequence MRI). Lymphovascular space invasion (LVSI) is allowed
2. Eligibility Criteria for Neoadjuvant Chemotherapy: Patients must be ≥18 years of age, and ≤40 years of age
3. Eligibility Criteria for Neoadjuvant Chemotherapy: Patients must be premenopausal and wish to preserve fertility
4. Eligibility Criteria for Neoadjuvant Chemotherapy: At time of registration, patient may not have had any prior therapy to treat their cancer lesion, patients with diagnostic cone or LEEP are allowed but a measurable tumor of >2 cm - ≤4 cm is mandatory
5. Eligibility Criteria for Neoadjuvant Chemotherapy: Eastern Cooperative Group (ECOG) performance status ≤ 2 (Karnofsky ≥60%, see Appendix C).
6. Eligibility Criteria for Neoadjuvant Chemotherapy: Within 14 days of the proposed start of treatment, patients must have normal organ and marrow function as defined:  Haemoglobin ≥ 100 g/L or ≥ 6.2 mmol/L  Leukocytes (WBC) ≥ 3.0x109 /L  absolute neutrophil count ≥1.5x109 /L  platelets ≥100x109 /L  total bilirubin within normal institutional limits  AST(SGOT) and ALT(SGPT) ≤2.5 × institutional upper limit of normal  creatinine within normal institutional limits
7. Eligibility Criteria for Neoadjuvant Chemotherapy: No evidence of active uncontrolled infection (patients on antibiotics are eligible).
8. Eligibility Criteria for Neoadjuvant Chemotherapy: Patient must have disease that is measurable per RECIST 1.1.
9. Eligibility Criteria for Neoadjuvant Chemotherapy: Ability to understand and willing to sign a written informed consent document.
10. Eligibility Criteria for Neoadjuvant Chemotherapy: Patients must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least one year after the FSS procedure. A serum pregnancy test within 7 days prior to study registration is required.
11. Eligibility Criteria for Fertility Sparing Surgery (FSS) Completed 3 cycles of neoadjuvant chemotherapy and achieved a complete response (CR) or partial response (PR) with reduction of the largest dimension of the lesion to <2 cm on physical examination and T2 sequence on MRI. For minimal MRI requirements: see Appendix F.

Exclusion criteria 11

1. Exclusion Criteria for Neoadjuvant Chemotherapy: Patients who have had chemotherapy or radiotherapy or surgery for their cancer. Patients with diagnostic cone or LEEP are allowed
2. Exclusion Criteria for Neoadjuvant Chemotherapy: Patients who are receiving any other investigational agents.
3. Exclusion Criteria for Neoadjuvant Chemotherapy: Patients with other cancers requiring ongoing treatment. Patients with malignancies unrelated to their cervical cancer can be included if they have not required treatment for 2 years. Patient with baso cellular skin cancer are allowed.
4. Exclusion Criteria for Neoadjuvant Chemotherapy: Patients with known / evidence of brain metastases are excluded from participation in this clinical trial.
5. Exclusion Criteria for Neoadjuvant Chemotherapy: History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, carboplatin, or cisplatin or other agents used in study.
6. Exclusion Criteria for Neoadjuvant Chemotherapy: Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Exclusion Criteria for Neoadjuvant Chemotherapy: Patients who are pregnant or breastfeeding
8. Exclusion Criteria for Neoadjuvant Chemotherapy: Any other condition that would, in the Investigator’s judgment, contraindicate the patient’s participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues.
9. Exclusion Criteria for Fertility Sparing Surgery: Patient unable to complete 3 cycles of neoadjuvant chemotherapy
10. Exclusion Criteria for Fertility Sparing Surgery: Suboptimal response to neoadjuvant chemotherapy according to local investigator
11. Exclusion Criteria for Fertility Sparing Surgery: Residual lesion > 2cm or disease progression while on chemotherapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To determine the rate of functional uterus defined as successful fertility sparing treatment (completion of neo-adjuvant chemotherapy (NACT) followed by fertility sparing surgery (FSS) and no adjuvant therapy)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Health Network

Sponsor organisation

University Health Network

Address

610 University Avenue

City

Toronto

Postcode

M5G 2M9

Country

Canada

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Departement of gynaecology

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Departement of gynaecology

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Departement of gynaecology

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Departement of gynaecology

Sponsor responsibilities

Article 77 compliance

University Health Network

Contact point sponsor

University Health Network

Article 77 implementation

University Health Network

Locations

2 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications