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Advanced Soft Tissue SarcomaPhase 2NCT03698227

OlaReDo - Olaratumab and Rechallenge With Doxorubicin in Soft Tissue Sarcoma Patients

A Phase 2 study testing Olaratumab, Dexrazoxane and Doxorubicin in people with Advanced Soft Tissue Sarcoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 4 sites in Germany.

Terminated

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

Official record
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Trial summary

This is an exploratory, prospective, open label, single arm, phase II-study for the evaluation of efficacy and feasibility (as determined by safety and tolerability) of olaratumab and doxorubicin rechallenge in anthracycline pretreated locally advanced (unresectable) or metastatic soft tissue sarcoma patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Soft Tissue Sarcoma
What is being tested?
Olaratumab, Dexrazoxane and Doxorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
4 sitesGermany
Study dates
12 Nov 2018to 25 Jun 2020
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

  • Patients must have histologically confirmed soft tissue sarcoma (STS) Note: Evidence of disease progression at study entry is required.
  • Treated in any order (neoadjuvant, adjuvant or for metastatic disease) with an anthracycline containing chemotherapy (The participant may have had any number of prior systemic cytotoxic therapies for advanced/metastatic disease. All previous anticancer treatments must be completed ≥ 3 weeks (21 days) prior to first dose of study drug.)
  • No progression on prior therapy with anthracyclines or within three months after stopping this therapy
  • Signed written informed consent
  • Men and women aged ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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  • Locally advanced (unresectable) or metastatic disease
  • Presence of measurable or non-measurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1, Eisenhauer et al. 2009)
  • Adequate haematologic, organ, and coagulation function within 2 weeks (14 days) prior to enrollment:
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3; G-CSF is not permitted within 2 weeks (14 days) prior to enrollment
  • Platelet count ≥ 100,000/mm3
  • Creatinine clearance ≥ 45 mL/min (calculated by using the Cockcroft-Gault formula (refer to study protocol Appendix 4)
  • Total bilirubin ≤ upper limit of normal (ULN). In patients with Gilbert's Syndrome, total bilirubin should be < 3 mg/dL
  • AST/ALT ≤ 3.0 x upper limit of normal (ULN); in case of liver involvement, AST/ALT ≤ 5.0 x are acceptable
  • Haemoglobin ≥ 9 g/dl. If haemoglobin <9 g/dl, blood transfusion is permitted. If haemoglobin cannot be enhanced to ≥ 9 g/dl, patient cannot be included into the study
  • International Normalized Ration (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 x ULN
  • Partial thromboplastin time (PTT or aPTT) ≤ 1.5 x ULN if not on anticoagulant therapy. For patients receiving anticoagulants, coagulation parameters within the intended or expected range for their therapeutic use are allowed. Patients must have no history of active bleeding (defined as within 14 days of first dose of study drug) or pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or known esophageal varices)
  • If routine urinalysis ≥2+ proteinuria, patient must have ≤1000 mg protein on a 24-hour urine, or urine protein/creatinine ratio ≤1 on spot urine
  • Left ventricular ejection fraction (LVEF) ≥50% assessed within 28 days prior to enrollment
  • Females of child-bearing potential must have a negative serum pregnancy test within 7 days prior to enrollment (refer to study protocol Appendix 3)
  • Females of child-bearing potential and males and must agree to use highly effective contraceptive precautions during the trial and up to 6 months following the last dose of study drug (refer to study protocol Appendix 3)
  • The participant has, in the opinion of the investigator, a life expectancy of at least 3 months

Who cannot join

  • Diagnosis of GIST or Kaposi sarcoma
  • Active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment. Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days and are not receiving systemic corticosteroids and/or anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment to rule out brain metastasis
  • Prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation
  • The participant has symptomatic congestive heart failure (CHF), or severe cardiac arrhythmia
  • The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction within 6 months of enrollment
  • The participant has a QTcB interval calculated using Bazett's formula interval of >450 milliseconds (msec) for males and >470 msec for females on screening electrocardiogram (ECG)
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  • Females who are pregnant or breastfeeding
  • Known allergy to any of the treatment components including a history of allergic reactions attributed to compounds of chemical or biological composition similar to olaratumab, dexrazoxane or doxorubicin
  • The participant has a known active fungal, bacterial, or viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required)
  • Known history of active bleeding (defined as within 14 days of first dose of study drug) or pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or known esophageal varices)
  • History of another primary cancer, with the exception of i) curatively treated non-melanomatous skin cancer or ii) curatively treated cervical carcinoma in situ or iii) other primary non-haematologic malignancies or solid tumor treated with curative intent, no known active disease and no treatment administered during the last 3 years prior to enrollment
  • Electively planned or required major surgery during the course of the clinical trial
  • Any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements
  • On-treatment participation in another clinical study in the period 30 days prior to start of study treatment and during the study
  • Legal incapacity or limited legal capacity
  • Any condition that requires concomitant vaccination with yellow fever vaccine

Trial locations and contacts

4 sites in 1 country.

Germany4 sites

  • Helios Klinikum Bad Saarow

    Bad Saarow, 15526

  • Helios Klinikum Berlin-Buch Klinik für Onkologie und Palliativmedizin

    Berlin, 13125

  • Charité Universitätsmedizin Berlin Medizinische Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie Campus Virchow Kliniken

    Berlin, 13353

  • Medizinische Fakultät Carl Gustav Carus Medizinische Klinik I Internistische Onkologie

    Dresden, 01307

Other trials in Germany

About this study

Official title: Efficacy of Olaratumab and Rechallenge With Doxorubicin in Anthracycline Pretreated, Advanced Soft Tissue Sarcoma Patients. An Exploratory Phase-II Study

This is an exploratory, prospective, open label, single arm, phase II-study for the evaluation of efficacy and feasibility (as determined by safety and tolerability) of olaratumab and doxorubicin rechallenge in anthracycline pretreated locally advanced (unresectable) or metastatic soft tissue sarcoma patients.

Read the detailed description

Until now, rechallenge with anthracyclines in patients with metastatic STS which had a benefit from prior anthracycline containing therapy was never investigated in a prospective study.

Due to the very promising effect of olaratumab and doxorubicin in anthracycline-naïve patients and further taking into consideration the results of the retrospective anthracycline rechallenge study, there is a clear rationale to evaluate the effects of olaratumab and doxorubicin also in anthracycline pretreated patients by conducting a prospective clinical trial.

Being tested
Olaratumab, Dexrazoxane, Doxorubicin
Keywords
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.

  • OlaratumabDrug

    Also called Study treatment

    iv infusion

  • DexrazoxaneDrug

    Also called Study treatment

    iv infusion

  • DoxorubicinDrug

    Also called Study treatment

    iv infusion

Study groups in NCT03698227
Study groupRoleWhat they receive
Study treatmentExperimental* Olaratumab 20 mg/kg IV on day 1 and day 8 of cycle 1 and 15 mg/kg olaratumab IV on day 1 and day 8 of cycles 2-8. * Plus dexrazoxane at a dose equal to 10 times the doxorubicin dose (mg/m2) IV on day 1 of each 21 day cycle for 8 cycles * Plus doxorubicin 75 mg/m2 IV on day 1 of each 21 day cycle for 8 cycles * Beginning with cycle 9, olaratumab maintenance monotherapy at 15 mg/kg IV on day 1 and day 8 of each subsequent 21 day cycle
Receives: Drug: Olaratumab; Drug: Dexrazoxane; Drug: Doxorubicin

What is being measured

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

  1. Progression-free survival rate after 3 months (PFSR3), assessed by applying RECIST 1.1

    number of patients proven progression-free and alive after 3 months divided through the total number of patients in the all-treated-subjects population

    Measured: After 3 months treatment

Secondary outcomes (6)

  1. Progression free survival (PFS)

    Time from the first dosing date of any study medication to the date of the first Objectively documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause.

    Measured: 6 months of Follow Up

  2. Objective response rate (ORR) (i.e. CR or PR)

    Number and percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR)

    Measured: 6 months of Follow Up

  3. Disease control rate (DCR) (i.e. CR, PR or SD)

    Number and percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD)

    Measured: 6 months of Follow Up

  4. Overall survival (OS)

    Time from date of the first dosing date of any study medication to the date of death (due to any cause)

    Measured: 6 months of Follow Up

  5. Assessment of adverse events

    Type, incidence and severity of AEs, SAEs

    Measured: During study conduct up to a maximum of 18 months (EOT)

  6. Study therapy discontinuation rate due to cardiac toxicity

    Number of patients proven study therapy discontinuation due to cardiac toxicity (i.e. due to LVEF reduction by more than 20% or LVEF <45%) divided through the total number of patients in the all-treated-subjects population

    Measured: After treatment discontinuation up to a maximum of 18 months (EOS)

Timeline

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

  1. First posted5 Oct 2018
  2. Study start12 Nov 2018
  3. Primary completion25 Jun 2020
  4. Study completion25 Jun 2020

Why it stopped: Lack of efficacy on olaratumab

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
Not applicable
Intervention model
Single group
Model description
Olaratumab and doxorubicin rechallenge in anthracycline pretreated, advanced soft tissue sarcoma patients
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03698227
Sponsor's protocol ID
OlaReDo_GISG-17
Status last verified
Jul 2020
First submitted
1 Oct 2018
Last updated
15 Jul 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Olaratumab, Dexrazoxane and Doxorubicin in people with Advanced Soft Tissue Sarcoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 4 sites in Germany.

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 22 inclusion and 16 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 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Germany. 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: Lack of efficacy on olaratumab). 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 rate after 3 months (PFSR3), assessed by applying RECIST 1.1 (time frame: After 3 months treatment). 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 NCT03698227.

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 15 Jul 2020.

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