Ph II Nintedanib vs. Ifosfamide in Soft Tissue Sarcoma

NCT02808247 | Terminated Phase 2 DMC

• 2 other identifiers: EORTC-1506-STBSG2016-002093-12
• Study Type: interventional
• Target: 80
• Locations: 7 countries
• Sites: 13

Brief Summary

This is a prospective, multicentric, randomized, open label Phase II trial investigating whether the oral angiogenesis inhibitor nintedanib, as compared to the intravenous cytotoxic compound ifosfamide, given for patients with advanced, inoperable and/or metastatic STS after failure of first line chemotherapy prolongs progression-free survival. The primary objective of the trial is to evaluate whether nintedanib given as second-line therapy for advanced, inoperable and/or metastatic STS prolongs progression-free survival when compared with ifosfamide. Secondary objectives are to evaluate the efficacy of nintedanib as compared to ifosfamide in terms of progression-free survival rate at 12 weeks, overall survival, objective response rate, patient benefit rate, response duration, total duration of treatment with nintedanib safety, Health related Quality of Life and Health Economics. Exploratory objectives include an analysis of putative predictive biomarkers for the anti-tumor effects of the investigational agent nintedanib.treatment.

Conditions

Sarcoma, Soft Tissue

Keywords

advanced metastatic soft tissue sarcoma

Outcome Measures

Primary Outcomes (1)

• progression-free survival (PFS)

  progression-free survival (PFS) defined according to RECIST 1.1.

  4 years from first patient in

Secondary Outcomes (9)

• Progression-free survival rate at 12 weeks (binary)

  4 years from first patient in

• Overall survival

  4 years from first patient in

• Objective response rate

  4 years from first patient in

• Clinical benefit rate

  4 years from first patient in

• Response duration

  4 years from first patient in

Study Arms (2)

Experimental arm (arm A): Nintedanib

EXPERIMENTAL

Nintedanib 200 mg twice daily orally. Nintedanib will be given continuously until clinically relevant disease progression according to the investigator's assessment or until other criteria for treatment discontinuation are met as specified in the protocol. Dosing beyond RECIST 1.1 progression is allowed for the oral agent if the patient still derives benefit from the treatment.

Drug: Nintedanib

Standard arm (arm B): Ifosfamide

ACTIVE COMPARATOR

Ifosfamide 3 g/m2 intravenously on days 1, 2 and 3 every 21 days for up to a maximum of 6 cycles.

Drug: Ifosfamide

Interventions

Nintedanib DRUG

Pharmaceutical form: Soft gelatine capsule Pharmaceutical code: Nintedanib (BIBF1120) Source: Boehringer Ingelheim Pharma GmbH \& Co. KG Unit strength: 100 mg and 150 mg capsules Daily dose: 400 mg (200 mg twice daily p.o.) Route of administration: oral

Also known as: BIBF1120

Experimental arm (arm A): Nintedanib

Ifosfamide DRUG

Ifosfamide will be given at a dose of 3 g/m2 intravenously on days 1, 2 and 3 every 21 days. The total dose per cycle is 9 g/m2

Standard arm (arm B): Ifosfamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Histologically proven advanced, inoperable and/or metastatic malignant STS of intermediate or high grade, excluding the:
• Well-differentiated liposarcoma/atypical lipoma
• Embryonal rhabdomyosarcoma
• Chondrosarcoma (extraskeletal myxoid chondrosarcoma is eligible)
• Osteosarcoma (extraskeletal osteosarcoma is eligible)
• Ewing family of tumors/primitive neuroectodermal tumor
• Gastro-intestinal stromal tumor
• Dermatofibrosarcoma protuberans
• For STS where no established grading system exists, or sarcoma subtypes which are very indolent or have an unpredictable clinical behavior, patient entry requires prospective approval in writing, on a case-by-case basis by the Study Coordinator of this trial and EORTC Headquarters (HQ).
• Representative formalin fixed, paraffin embedded tumor blocks or unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review. Histological central review is not required before treatment start but it is mandatory to send unstained tumor slides (blocks optional) at time of study entry. Local histopathological diagnosis will be accepted for entry into this trial.
• Prior to study enrolment, all patients need to have confirmed RECIST 1.1 disease progression based on local investigator's assessment.
• Presence of measurable disease according to RECIST 1.1.
• Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered non-measurable unless there has been demonstrated progression (20 % increase) in the assessed lesion since the local treatment.
• No radiographic evidence of cavitary lesions (either primary tumor or metastatic lesions).
• No centrally located tumors with radiographic evidence of local invasion of major blood vessels.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Boehringer Ingelheim: collaborator

Study Sites (13)

Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet

Brussels, 1000, Belgium

Location

Cliniques Universitaires Saint-Luc (121)

Brussels, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg (147)

Leuven, Belgium

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Leon Berard (227)

Lyon, France

Location

Gustave Roussy (225)

Villejuif, France

Location

Vilnius University Hospital Santariskiu Santaros Clinics Klinikos (9453)

Vilnius, 08661, Lithuania

Location

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis (301)

Amsterdam, 1066, Netherlands

Location

Leiden University Medical Centre (310)

Leiden, 2300, Netherlands

Location

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, 02 781, Poland

Location

Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)

Barcelona, 08916, Spain

Location

Hospital Universitario San Carlos (366)

Madrid, 28040, Spain

Location

Royal Marsden Hospital - Chelsea, London (613)

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• Schoffski P, Toulmonde M, Estival A, Marquina G, Dudzisz-Sledz M, Brahmi M, Steeghs N, Karavasilis V, de Haan J, Wozniak A, Cousin S, Domenech M, Bovee JVMG, Charon-Barra C, Marreaud S, Litiere S, De Meulemeester L, Olungu C, Gelderblom H. Randomised phase 2 study comparing the efficacy and safety of the oral tyrosine kinase inhibitor nintedanib with single agent ifosfamide in patients with advanced, inoperable, metastatic soft tissue sarcoma after failure of first-line chemotherapy: EORTC-1506-STBSG "ANITA". Eur J Cancer. 2021 Jul;152:26-40. doi: 10.1016/j.ejca.2021.04.015. Epub 2021 May 29.

  PMID: 34062484 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

nintedanib; Ifosfamide

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Patrick Schoeffski, MD

  U.Z. Leuven - Campus Gasthuisberg (147)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: June 21, 2016
• Study Start: July 7, 2017
• Primary Completion: November 3, 2020
• Study Completion: April 14, 2021
• Last Updated: September 20, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); LI (1); NL (2); PL (1); GB (1); BE (3); FR (3)