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

NCT03698227 | Terminated Phase 2 DMC

• 1 other identifier: OlaReDo_GISG-17
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Advanced Soft Tissue Sarcoma

Keywords

Soft tissue sarcoma

Outcome Measures

Primary Outcomes (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

  After 3 months treatment

Secondary Outcomes (6)

• Progression free survival (PFS)

  6 months of Follow Up

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

  6 months of Follow Up

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

  6 months of Follow Up

• Overall survival (OS)

  6 months of Follow Up

• Assessment of adverse events

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

Study Arms (1)

Study treatment

EXPERIMENTAL

* 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

Drug: Olaratumab; Drug: Dexrazoxane; Drug: Doxorubicin

Interventions

Olaratumab DRUG

iv infusion

Also known as: Study treatment

Study treatment

Dexrazoxane DRUG

iv infusion

Also known as: Study treatment

Study treatment

Doxorubicin DRUG

iv infusion

Also known as: Study treatment

Study treatment

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (4)

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Helios Klinikum Berlin-Buch Klinik für Onkologie und Palliativmedizin

Berlin, 13125, Germany

Location

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

Berlin, 13353, Germany

Location

Medizinische Fakultät Carl Gustav Carus Medizinische Klinik I Internistische Onkologie

Dresden, 01307, Germany

Location

MeSH Terms

Conditions

Sarcoma

Interventions

olaratumab; Pharmaceutical Preparations; Dexrazoxane; Doxorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Razoxane; Diketopiperazines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Olaratumab and doxorubicin rechallenge in anthracycline pretreated, advanced soft tissue sarcoma patients

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: October 5, 2018
• Study Start: November 12, 2018
• Primary Completion: June 25, 2020
• Study Completion: June 25, 2020
• Last Updated: July 15, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)