AzTrials
AzTrials

Sarcoma, Soft TissuePhase 2ANITANCT02808247

Ph II Nintedanib vs. Ifosfamide in Soft Tissue Sarcoma

A Phase 2 study testing Nintedanib and Ifosfamide in people with Sarcoma, Soft Tissue, run by European Organisation for Research and Treatment of Cancer - EORTC at 13 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sarcoma, Soft Tissue
What is being tested?
Nintedanib and Ifosfamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
13 sitesin 7 countries
Study dates
7 Jul 2017to 14 Apr 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 63Show fewer
  • 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.
  • No history of central nervous system metastasis or leptomeningeal tumor spread.
  • No active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomization).
  • One (and no less or more than one) line of previous systemic chemotherapy for advanced, inoperable and/or metastatic malignant STS.
  • Prior neoadjuvant, adjuvant and or first-line maintenance systemic chemotherapy for locally advanced or metastatic STS is allowed and does count as zero lines of treatment, provided that the disease did not progress during neoadjuvant and/or adjuvant therapy or within 12 weeks after completion of the perioperative treatment. In case the disease progressed during neoadjuvant, adjuvant and or first-line maintenance systemic chemotherapy or within 12 weeks after its completion, the treatment is counted as one line and the patient can theoretically participate in the trial, provided all other selection criteria are met.
  • No prior exposure to an oxazaphosphorine agent, including but not limited to ifosfamide, cyclophosphamide, trofosfamide or evofosfamide (TH-302).
  • No prior exposure to oral or intravenous angiogenesis inhibitors, including but not limited to tyrosine kinase inhibitors such as pazopanib, sunitinib, sorafenib, axitinib or similar or monoclonal antibodies targeting angiogenesis.
  • No other anti-cancer therapy (systemic therapy, radiotherapy (except for brain and extremities), surgery, limb perfusion, immunotherapy) within 28 days prior to randomization.
  • No treatment with another investigational agent within 28 days prior to randomization.
  • No treatment with another investigational agent concomitantly with the trial.
  • No known hypersensitivity to or known specific contraindications for the use of nintedanib or ifosfamide.
  • No known hypersensitivity to peanut or soy bean.
  • Age 18 years or older.
  • WHO performance status (PS) 0-2.
  • Life expectancy of at least 3 months.
  • Adequate bone marrow, liver and renal function and coagulation parameters:
  • neutrophils ≥ 1.5 x 109/L;
  • hemoglobin ≥ 9 g/dL (or ≥ 5.6 mmol/L). Blood transfusions or the administration of hematopoietic growth factors are allowed to achieve these baseline values;
  • platelets ≥ 100 x 109/L. Platelet transfusions or the administration of hematopoietic growth factors are allowed to achieve these baseline values;
  • Total bilirubin ≤ ULN;
  • Patients with Gilbert syndrome and/or bilirubin < 2xULN and normal AST/ALT are eligible;
  • SGPT/ALT and SGOT/AST ≤ 2.5 x ULN for patients with liver metastasis;
  • SGPT/ALT and SGOT/ AST ≤ 1.5x ULN for patients without liver metastasis;
  • Serum creatinine or creatinine clearance/eGFR within normal limits to baseline, assessed as per local standard method;
  • No proteinuria CTCAE grade 2 or greater;
  • International normalized ratio (INR) ≤ 2;
  • Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 50% of institutional ULN.
  • No Child Pugh B or C hepatic impairment.
  • Normal cardiac function (left ventricular ejection fraction (LVEF) assessed by multi-gated acquisition scan or cardiac ultrasound within normal range of the institution), 12 lead electrocardiogram (ECG) without clinically relevant abnormalities. No Class III or IV congestive heart failure, angina pectoris, myocardial infarction within 1 year before registration/randomization, clinically significant cardiac arrhythmia or pericardial effusion.
  • No uncontrolled arterial hypertension defined at baseline as blood pressure ≥ 150/100 mmHg despite adequate medical therapy.
  • No use of therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325 mg per day).
  • No known inherited predisposition for bleeding or thromboembolism.
  • No history of clinically significant hemorrhagic or thromboembolic event in the past 6 months.
  • Absence of active or uncontrolled infections in particular if requiring systemic antibiotics or antimicrobial therapy.
  • No previous encephalopathy of any cause or other significant neurological condition.
  • No acute or chronic, clinically relevant inflammation of urinary bladder.
  • Absence of serious illnesses or medical conditions, including a history of chronic alcohol abuse, active and chronic hepatitis B or C, chronic infection with HIV or clinically relevant liver cirrhosis.
  • Absence of active gastrointestinal disorders or abnormalities that interfere with absorption of the study drug.
  • No major injuries and/or surgery within the past 28 days prior to randomization with incomplete wound healing and/or planned surgery during the on-treatment study period.
  • No persistence of clinically relevant therapy-related toxicity from previous chemotherapy and/or radiotherapy. Grade 1 or 2 adverse events (AEs) are acceptable.
  • No history, within the past five years, of malignancies other than STS (except: basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, resected prostate cancer staged pT1-2 with Gleason Score ≤ 6 and postoperative PSA < 0.5 ng/ml). Patients with a history of other malignancies who are disease-free from that condition for more than 5 years are eligible.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration/randomization in the trial.
  • No active alcohol or drug abuse.
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to randomization.
  • Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 3 months (nindetanib) and 6 months (ifosfamide) after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Since the effect of nintedanib on the metabolism and efficacy of contraceptives has not been investigated, barrier methods should be applied as a second form of contraception, to avoid pregnancy.
  • Female subjects who are breast feeding should discontinue nursing prior to randomization and until 6 months after the last study treatment.
  • Sexually active male participants must use a barrier method of contraception (e.g., condom) during the study treatment period and for at least 3 months after the last study treatment.
  • Before patient registration/randomization, written informed consent must be obtained according to international conference on harmonisation/Good clinical practice (ICH/GCP) and national/local regulations.
  • Patients can only be randomized in this trial once. Important note: All eligibility criteria must be adhered to, in case of potential deviation a discussion with EORTC Headquarters and study coordinator is mandatory.

Who cannot join

None listed.

Trial locations and contacts

13 sites in 7 countries.

13 sites in 7 countries

Belgium3 sites

  • Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet

    Brussels, 1000

  • Cliniques Universitaires Saint-Luc (121)

    Brussels

  • U.Z. Leuven - Campus Gasthuisberg (147)

    Leuven

Other trials in Belgium

France3 sites

  • Institut Bergonie

    Bordeaux, 33076

  • Centre Leon Berard (227)

    Lyon

  • Gustave Roussy (225)

    Villejuif

Other trials in France

Netherlands2 sites

  • The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis (301)

    Amsterdam, 1066

  • Leiden University Medical Centre (310)

    Leiden, 2300

Other trials in Netherlands

Spain2 sites

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

    Barcelona, 08916

  • Hospital Universitario San Carlos (366)

    Madrid, 28040

Other trials in Spain

Lithuania1 site

  • Vilnius University Hospital Santariskiu Santaros Clinics Klinikos (9453)

    Vilnius, 08661

Other trials in Lithuania

Poland1 site

  • Maria Sklodowska-Curie Memorial Cancer Centre

    Warsaw, 02 781

Other trials in Poland

United Kingdom1 site

  • Royal Marsden Hospital - Chelsea, London (613)

    London, SW3 6JJ

Other trials in United Kingdom

About this study

Official title: A Phase II Multicenter Study Comparing the Efficacy of the Oral Angiogenesis Inhibitor Nintedanib With the Intravenous Cytotoxic Compound Ifosfamide for Treatment of Patients With Advanced Metastatic Soft Tissue Sarcoma After Failure of Systemic Non-oxazaphosporine-based First Line Chemotherapy for Inoperable Disease "ANITA"

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.

Read more

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.

Being tested
Nintedanib, Ifosfamide
Keywords
advanced metastatic soft tissue sarcoma
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NintedanibDrug

    Also called BIBF1120

    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

  • IfosfamideDrug

    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

Study groups in NCT02808247
Study groupRoleWhat they receive
Experimental arm (arm A): NintedanibExperimentalNintedanib 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.
Receives: Drug: Nintedanib
Standard arm (arm B): IfosfamideActive comparatorIfosfamide 3 g/m2 intravenously on days 1, 2 and 3 every 21 days for up to a maximum of 6 cycles.
Receives: Drug: Ifosfamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. progression-free survival (PFS)

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

    Measured: 4 years from first patient in

Secondary outcomes (9)

  1. Progression-free survival rate at 12 weeks (binary)

    Measured: 4 years from first patient in

  2. Overall survival

    Measured: 4 years from first patient in

  3. Objective response rate

    Objective tumor response as defined by RECIST 1.1

    Measured: 4 years from first patient in

  4. Clinical benefit rate

    Measured: 4 years from first patient in

  5. Response duration

    Duration of response will be measured for patients achieving an objective response

    Measured: 4 years from first patient in

  6. Total duration of treatment with nintedanib (including treatment beyond RECIST progression)

    Measured: 4 years from first patient in

  7. Safety (Common Toxicity Criteria CTCAE 4.0)

    Measured: 4 years from first patient in

  8. Health related quality of life (QLQ-C30)

    Quality of life will be assessed with the EORTC QoL Questionnaire (QLQ-C30) version 3.0

    Measured: 4 years from first patient in

  9. Health economics (EQ-5D-5L, health care resource utilities)

    Patient reported utility: EQ-5D-5L

    Measured: 4 years from first patient in

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2016 (estimated)
  2. Study start7 Jul 2017
  3. Primary completion3 Nov 2020
  4. Study completion14 Apr 2021

Why it stopped: Exceed of pre-specified number of failures in the experimental arm

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02808247
Sponsor's protocol ID
EORTC-1506-STBSG
Other IDs
2016-002093-12, 2016
Acronym
ANITA
Status last verified
Sep 2021
First submitted
17 Jun 2016
Last updated
20 Sep 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34062484

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nintedanib and Ifosfamide in people with Sarcoma, Soft Tissue, run by European Organisation for Research and Treatment of Cancer - EORTC at 13 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 63 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Belgium, France, Netherlands, Spain, Lithuania and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Exceed of pre-specified number of failures in the experimental arm). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

progression-free survival (PFS) (time frame: 4 years from first patient in). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02808247, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2021; AzTrials last refreshed its copy on 1 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in