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

Sponsor

Belgian Gynaecological Oncology Group (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02009579

Collaborator

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

120

Enrollment

Locations

Arms

115

Duration (Months)

3.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Uterine Cervical Neoplasms	Drug: Nintedanib Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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."

Study Start Date :

Mar 1, 2014

Actual Primary Completion Date :

Jan 1, 2021

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Experimental arm Nintedanib/vargatef	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. Other Names: Vargatef
Placebo Comparator: Comparator arm Placebo	Drug: 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.

Arm

Intervention/Treatment

Active Comparator: Experimental arm

Nintedanib/vargatef

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.

Other Names:

Vargatef

Placebo Comparator: Comparator arm

Placebo

Drug: 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.

Outcome Measures

Primary Outcome Measures

Progression free survival [1.5 years after LPI]
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.

Secondary Outcome Measures

Safety and toxicity [5 years after LPI]
Secondary objectives: To evaluate the safety and toxicity reported for of the combination regimen
Overall survival [5 years after LPI]
To evaluate the response rate according to RECIST 1.1
Patient health status [5 years after LPI]
To explore the effect of Nintedanib on patient reported health status as measured by EORTC-QOL-Cx 24 and EORTCQLQ-C30 questionnaires
Overall survival [5 years after LPI]
To evaluate the overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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 (β-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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Saint-Pierre	Bruxelles	Belgium
2	Institut Jules Bordet	Bruxelles	Belgium
3	Grand Hopital de Charleroi	Charleroi	Belgium
4	UZ Antwerpen	Edegem	Belgium
5	AZ Groeninge	Kortrijk	Belgium
6	UZ Leuven	Leuven	Belgium	3000
7	CHR Citadelle	Liege	Belgium
8	CHU de Liège	Liège	Belgium	4000
9	Clinique et maternite St. Elisabeth	Namur	Belgium
10	Cliniques Universitaires mont godinne	Yvoir	Belgium
11	Charité Med Uni Berlin	Berlin	Germany
12	Universitätsklinikum Carl Gustav Carus Dresden	Dresden	Germany
13	Kliniken Essen Mitte	Essen	Germany
14	Georg-August University Göttingen	Gottingen	Germany
15	Medical University Greifswald	Greifswald	Germany
16	University Tübingen	Tubingen	Germany
17	Centro Riferimento Oncologico	Aviano	Italy
18	Spedali Civili	Brescia	Italy
19	Azienda Ospedaliera Cannizzaro	Catania	Italy
20	National Cancer Institute	Milano	Italy
21	Istituto Nazionale Tumori-Pascale Naples	Naples	Italy
22	Padova Istituti Oncologico Veneto	Padova	Italy
23	University Pisa	Pisa	Italy
24	AUSL Reggio Emilia	Reggio Emilia	Italy
25	Poloclinico A Gemelli	Rome	Italy
26	Mauriziano -Torino	Torino	Italy
27	S. Anna Torino	Torino	Italy
28	Hospital Provincial Reina Sofia	Córdoba	Spain	14004
29	H. Ramón y Cajal	Madrid	Spain	28034
30	Hospital Clinico San Carlos	Madrid	Spain	28040
31	Hospital Universitario Morales Meseguer	Murcia	Spain	30008
32	Hospital Son Llatzer	Palma Mallorca	Spain	07198