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Olaratumab Plus Trabectedin in Advanced Soft-tissue Sarcoma Patients Soft-tissue Sarcoma Patients (OLATRASTS)

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ClinicalTrials.gov Identifier: NCT03985722
Recruitment Status : Recruiting
First Posted : June 14, 2019
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Grupo Espanol de Investigacion en Sarcomas

Brief Summary:

Phase I, multicentre clinical trial of olaratumab plus trabectedin in patients with advanced soft-tissue sarcoma.

Olaratumab plus trabectedin could be synergistic and with a manageable toxicity profile in advanced STS.

The study is a phase I, non-randomised, one-armed, multicenter trial, open-label.

The dose escalation rules include patients in blocks of 3 o 6 patient. Treatment is a combination of unlimited cycles of oralatumab and trabectedin.

Primary clinical study endpoint of phase I

  • Determine the maximum tolerated dose (MTD) or the recommended dose of olaratumab combined with trabectedin in advanced soft tissue sarcoma.

Secondary clinical study endpoints

  • Objective Response Rate (ORR): ORR is defined as the number of subjects with a Best Overall Response (BOR) according to RECIST 1.1.
  • Correlation of clinical outcome with translational biomarkers.
  • Quality of life (QoL) measured per QLQ-C30 questionnaire of EORTC.

Condition or disease Intervention/treatment Phase
Sarcoma, Soft Tissue Drug: Olaratumab and Trabectedin Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Intervention Model Description:

The study is a phase I, non-randomised, one-armed, multicenter trial, open-label.

The dose escalation rules include patients in blocks of 3 o 6 patient. See chapter 5 for more details.

Treatment is a combination of unlimited cycles of oralatumab and trabectedin.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial of Olaratumab Plus Trabectedin in Advanced Soft-tissue Sarcoma Patients
Actual Study Start Date : September 21, 2018
Estimated Primary Completion Date : August 5, 2019
Estimated Study Completion Date : May 5, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Unlimited cycles of Olaratumab and Trabectedin

The study is a phase I, non-randomised, one-armed, multicenter trial, open-label,.

The dose escalation rules include patients in blocks of 3 o 6 patient. Treatment is a combination of unlimited cycles of oralatumab and trabectedin.

Drug: Olaratumab and Trabectedin

Dose-escalation levels:

LEVEL -1: Olaratumab 15 mg/Kg D1 and D8 + Trabectedin 0.9 mg/m2 D1 This is a security level in case level 0 causes DLT.

LEVEL 0*: Olaratumab 15 mg/Kg D1 and D8 + Trabectedin 1.1 mg/m2 D1.

* Dose starting level is 0.

Other Name: Lartruvo and Yondelis

Drug: Olaratumab and Trabectedin

Dose-escalation levels:

LEVEL 2: Olaratumab 15 mg/Kg D1 and D8 + Trabectedin 1.5 mg/m2 D1

Other Name: Lartruvo and Yondelis

Drug: Olaratumab and Trabectedin

Dose-escalation levels:

LEVEL 3**: Olaratumab 20 mg/kg C1D1 and C1D8 (induction) + Trabectedin 1.5 mg/m2 D1 and Olaratumab 15 mg/kg D1 and D8 (maintenance) + Trabectedin 1.5 mg/m2 D1

**In the LEVEL 3 Olaratumab dose of 20 mg/kg will be considered only for the first 2 doses (as induction doses, cycle 1 days 1 and 8)) and then, the maintenance dose will be 15 mg/m2 for the rest of cycles.

Other Name: Lartruvo and Yondelis




Primary Outcome Measures :
  1. To determine the maximum tolerated dose (MTD) or the recommended dose for phase II of Olaratumab plus Trabectedin. [ Time Frame: Recruitment duration: 18 months ]
    There will be determined the security profile for each dose level.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR): ORR is defined as the number of subjects with a Best Overall Response (BOR) according to RECIST 1.1. [ Time Frame: Recruitment duration: 18 months ]
    Objective Response Rate (ORR): ORR is defined as the number of subjects with a Best Overall Response (BOR) according to RECIST 1.1.

  2. Correlation of clinical outcome with translational biomarkers (See Translational Section) [ Time Frame: Recruitment duration: 18 months ]
    Correlation of clinical outcome with translational biomarkers (See Translational Section)

  3. QoL measured per QLQ-C30 questionnaire of EORTC. [ Time Frame: Recruitment duration: 18 months ]
    QoL measured per QLQ-C30 questionnaire of EORTC.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must provide written informed consent prior to performance of study-specific procedures and must be willing to comply with treatment and follow up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient's routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.
  2. Age: 18-80 years.
  3. Histologic diagnosis of soft tissue sarcoma: Liposarcoma (dedifferentiated and myxoid/round cell liposarcomas), leiomyosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma confirmed, after enrolment, by central pathology review by paraffin embedded tumor tissue.
  4. Metastatic/advanced and measurable disease in progression in the last 6 months.
  5. Patients have had previously received at least anthracyclines. Previous olaratumab administration is allowed.
  6. Measurable disease according to RECIST 1.1 criteria.
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  8. Adequate hepatic, renal, cardiac, and hematologic function.
  9. Laboratory tests as follows:

    • Absolute neutrophil count ≥ 1,500/mm³
    • Platelet count ≥ 100,000/mm³
    • Bilirubin ≤ 1.5 mg/dL
    • Protein Total (PT)≤ 1.5 upper limit normal (ULN) and Iinternational normalized ratio (NR) ≤ 1.5
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal
    • Creatinine ≤ 1.5 mg/dL
    • Calcium ≤ 12 mg/dL
    • Blood glucose < 150 mg/Dl
    • Urine protein assessment: <2 positive, and/or <3.5g protein/24h.
  10. Left ventricular ejection fraction ≥ 50% by echocardiogram or multi-unit gated analysis (MUGA) scan.
  11. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and agree to use birth control measures during study treatment and for 7 months after its completion. 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. A highly effective method of birth control is defined as one that results in a low failure rate (that is, <1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner.

Exceptions: Females not of child-bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause.

A "postmenopausal woman" is a woman meeting either of the following criteria:

  • spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications during the amenorrhea that induced the amenorrhea (for example, oral contraceptives, hormones, gonadotropin releasing hormone, antiestrogens, selective estrogen receptor modulators (SERMs), or chemotherapy
  • spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone (FSH) level >40 mIU/mL

Exclusion criteria

  1. No more than 2 previous lines previous lines of chemotherapy for advanced disease.
  2. The following histologies are not included: Ewing sarcoma, extraskeletal osteosarcoma, extraskeletal myxoid chondrosarcoma, Kaposi's sarcoma, rhabdomyosarcoma and gastrointestinal stromal tumor (GIST) .
  3. Uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI-CTCAE] version 4.0 Grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= Grade 3).
  4. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
  5. Other disease or illness within the past 6 months, including any of the following:

    • Myocardial infarction
    • Coronary or peripheral artery bypass graft
    • Cerebrovascular accident or transient ischemic attack
    • Pulmonary embolism
  6. Evidence of a bleeding diathesis.
  7. Uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy.
  8. The patient has electively planned or will require major surgery during the course of the study
  9. Social situation that would preclude study compliance.
  10. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication.
  11. Prolonged corrected QT interval (QTc interval) (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG.
  12. Hemorrhage ≥ Grade 3 in the past 4 weeks.
  13. Females who are pregnant or breast-feeding In the event of proposed combinations, additional inclusion/exclusion criteria and monitoring parameters might be required depending on the toxicity profile of the combination drug(s). These inclusion/exclusion criteria will only be implemented in case of patient safety reasons as Urgent Safety Measures and an Ad hoc report will be sent to Regulatory Agency and Ethic Committee before a Protocol amendment is evaluated.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03985722


Contacts
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Contact: Javier Martín Broto 0034 644289162 secretaria@grupogeis.org

Locations
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Spain
GEIS Recruiting
Madrid, Spain, 28006
Contact: María de Cuaresma, PM    0034 644289162    mariac.crc@grupogeis.org   
Contact: Melissa Fernandez, PM    0034 912866807    melissa.crc@grupogeis.org   
Sponsors and Collaborators
Grupo Espanol de Investigacion en Sarcomas
Investigators
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Study Chair: Javier MARTIN-BROTO, MD Hospital Virgen del Rocío

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Responsible Party: Grupo Espanol de Investigacion en Sarcomas
ClinicalTrials.gov Identifier: NCT03985722     History of Changes
Other Study ID Numbers: GEIS 58
2017-004771-32 ( EudraCT Number )
First Posted: June 14, 2019    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We are open to Individual participant data (IPD). Whenever there is a researcher interested in OLATRASTS raw data results, please contact the Study Chief to comment on the objectives and agreement of this sharing.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Grupo Espanol de Investigacion en Sarcomas:
advanced soft-tissue sarcoma

Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Trabectedin
Olaratumab
Antibodies, Monoclonal
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs