ENGOT-cx1/BGOG-cx1: 3 Weekly Carboplatin/Paclitaxel With or Without Nintedanib in Cervix Cancer

Uterine Cervical Neoplasms Clinical Trial

Official title:

BGOG-cx1/ENGOT-cx1: "Randomized Double-blind Phase II Study Comparing 3-weekly Carboplatin + Paclitaxel With or Without Concomitant and Maintenance Nintedanib (NINTEDANIB) in Advanced or Recurrent Cervical Carcinoma."

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02009579
• Other study ID #: BGOG-cx1/ENGOT-cx1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 2014
• Est. completion date: October 2023

Study information

• Verified date: July 2023
• Source: Belgian Gynaecological Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Indication:

Treatment of subjects with advanced (FIGO stage IVB) or recurrent cervical cancer, prior radiochemotherapy or neo-adjuvant chemotherapy is allowed.

Study design:

This is a phase II randomized, double blind and placebo controlled trial evaluating the efficacy of Nintedanib/placebo in combination with the standard carboplatin and paclitaxel followed by Nintedanib/placebo maintenance in the treatment of patients with advanced or recurrent cervical cancer.

A total of 120 patients will be randomized between the experimental and control arm in a 1:1 ratio. Randomization will be stratified for 1previous chemotherapy for metastatic disease (yes/no) and 2disease status (Stage IVB primary versus recurrent disease).

Experimental arm: Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and Nintedanib 200 mg BID followed by Nintedanib maintenance until progression or for a total maximum duration of 120 weeks.

Control arm: Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and placebo 200 mg BID followed by placebo maintenance until progression or for a total maximum duration of 120 weeks.

Subjects without evidence of disease progression after completion or discontinuation of the study treatment will be followed until radiographic disease progression, withdrawal of consent or death.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: October 2023
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female subjects more than 18 years of age

• Histologically or cytologically confirmed advanced ([FIGO] stage IVB), or recurrent/persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix will be eligible.

• Prior treatment with angiogenesis inhibitors is allowed

• Up to one prior line of chemotherapy for metastatic cervical cancer is allowed.

• Treatment of primary disease with concomitant cisplatinum chemotherapy during radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.

• Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery is allowed and does not count as a line of chemotherapy for metastatic disease.

• Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiochemotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.

• Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.

• Life expectancy at least 3 months.

• ECOG Performance status score of 0 or 1

• At least one measurable lesion according to RECIST 1.1 criteria

• Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation

Exclusion Criteria:

• Known hypersensitivity to the trial drugs or to their excipients (including peanut or soya).

• Brain or leptomeningeal metastases.

• Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels.

• Tumor infiltrating the mucosa of the bowel or bladder, or known fistulas between the tumor and the gastrointestinal or urinary tract.

• Radiographic evidence of cavitary or necrotic tumours

• Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial.

• Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid <325 mg per day).

• Major injuries within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.

• History of clinically significant haemorrhagic or thromboembolic event in the past 6 months.

• Known inherited predisposition to bleeding or thrombosis.

• Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina within the past 6 months, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion).

• History of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months.

• Abnormal renal, liver or bone marrow function defined as:

• Proteinuria CTCAE grade 2 or greater

• Creatinin > 2 ULN or GFR < 30 ml/min

• Hepatic function: total bilirubin outside of normal limits; ALT or AST > 1.5 ULN in pts without liver metastasis. For Pts with liver metastases: total bilirubin outside of normal limits, ALT or AST > 2.5 ULN

• Coagulation parameters: International normalised ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN

• Absolute neutrophil count ( ANC) < 1500/µl, platelets < 100000/µl, haemoglobin < 9.0 g/dl

• Other malignancies within the past 3 years or other malignancy with recurrence in the past 3 years or with high risk of recurrence in the first year. In exception to this rule, the following malignancies may be included: non-melanomatous skin cancer (if adequately treated) , any premalignant (e.g. in situ) carcinoma, or basocellular carcinoma.

• Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy.

• Active or chronic hepatitis C and/or B infection or known HIV infection (based on medical file, only for Italy a mandatory screening test for HIV should be performed for all patients who did not have this test within the last 3 months before the study treatment start).

• Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug.

• Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.

• Patients of child-bearing potential who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner or sexual abstinence for participating females) during the trial and for at least three months after end of active therapy.

• Pregnancy or breast feeding, female patients must have a negative pregnancy test (ß-HCG test in urine or serum) prior to commencing study treatment, if applicable.

• Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule.

• Active alcohol or drug abuse.

Related Conditions & MeSH terms

• Uterine Cervical Neoplasms

Intervention

Drug:
• Nintedanib
Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and Nintedanib 200 mg BID followed by Nintedanib maintenance until progression or for a total maximum duration of 120 weeks.
• Placebo
Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and placebo 200 mg BID followed by placebo maintenance until progression or for a total maximum duration of 120 weeks.

Locations

Country	Name	City	State
Belgium	CHU Saint-Pierre	Bruxelles
Belgium	Institut Jules Bordet	Bruxelles
Belgium	Grand Hopital de Charleroi	Charleroi
Belgium	UZ Antwerpen	Edegem
Belgium	AZ Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	CHR Citadelle	Liege
Belgium	CHU de Liège	Liège
Belgium	Clinique et maternite St. Elisabeth	Namur
Belgium	Cliniques Universitaires mont godinne	Yvoir
Germany	Charité Med Uni Berlin	Berlin
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Kliniken Essen Mitte	Essen
Germany	Georg-August University Göttingen	Gottingen
Germany	Medical University Greifswald	Greifswald
Germany	University Tübingen	Tubingen
Italy	Centro Riferimento Oncologico	Aviano
Italy	Spedali Civili	Brescia
Italy	Azienda Ospedaliera Cannizzaro	Catania
Italy	National Cancer Institute	Milano
Italy	Istituto Nazionale Tumori-Pascale Naples	Naples
Italy	Padova Istituti Oncologico Veneto	Padova
Italy	University Pisa	Pisa
Italy	AUSL Reggio Emilia	Reggio Emilia
Italy	Poloclinico A Gemelli	Rome
Italy	Mauriziano -Torino	Torino
Italy	S. Anna Torino	Torino
Spain	Hospital Provincial Reina Sofia	Córdoba
Spain	H. Ramón y Cajal	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Morales Meseguer	Murcia
Spain	Hospital Son Llatzer	Palma Mallorca

Sponsors (5)

Lead Sponsor	Collaborator
Belgian Gynaecological Oncology Group	Grupo Español de Investigación en Cáncer de Ovario, Mario Negri Gynecologic Oncology group (MaNGO), Multicenter Italian Trials in Ovarian Cancer (MITO), North Eastern German Society of Gynaecological Oncology

Countries where clinical trial is conducted

Belgium,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	Primary objective: The purpose of this trial is to determine if chemotherapy (carboplatin/paclitaxel) plus Nintedanib (BIBF 1120) can improve progression free survival compared to chemotherapy (carboplatin/paclitaxel) plus placebo in patients with advanced or recurrent cervical cancer.	1.5 years after LPI
Secondary	Safety and toxicity	Secondary objectives: To evaluate the safety and toxicity reported for of the combination regimen	5 years after LPI
Secondary	Overall survival	To evaluate the response rate according to RECIST 1.1	5 years after LPI
Secondary	Patient health status	To explore the effect of Nintedanib on patient reported health status as measured by EORTC-QOL-Cx 24 and EORTCQLQ-C30 questionnaires	5 years after LPI
Secondary	Overall survival	To evaluate the overall survival	5 years after LPI

External Links

•   BGOG website
•   ENGOT website