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Randomized Trial in Advanced, Metastatic or Unresectable Soft Tissue Sarcoma After Failure of Standard Treatments. (TOMAS2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03838744
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : November 1, 2021
Information provided by (Responsible Party):
Italian Sarcoma Group

Brief Summary:
Phase II study in patient with advanced Soft Tissue Sarcoma (STS) patients who have already received or are not suitable, for a doxorubicin-based treatment.

Condition or disease Intervention/treatment Phase
Advanced Soft Tissue Sarcoma Drug: Standard arm: Trabectedin in monotherapy Drug: Experimental arm: Trabectedin + Olaparib Phase 2

Detailed Description:
Randomized, open-label, active-controlled, multicenter phase II clinical study. Patients will be randomly assigned in a 1:1 ratio to receive trabectedin 1.1 mg/m2 24-hour intravenous continuous infusion every 3 weeks with olaparib (per os) 150 mg twice a day versus trabectedin 1.5 mg/m2 intravenous 24-hour continuous infusion every 3 weeks until progression or unacceptable toxicity as second- or further-line treatment in a population of STS patients who have already received or are not suitable for a doxorubicin-based treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Controlled, parallel, two arm study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Randomized Trial of Trabectedin + Olaparib vs. Trabectedin in Advanced, Metastatic or Unresectable Soft Tissue Sarcoma After Failure of Standard Treatments.
Actual Study Start Date : May 26, 2020
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Standard arm: Trabectedin in monotherapy
Trabectedin in monotherapy at the dose 1.5 or 1.3 mg/m2 (according institutional practice) given as intravenous infusion at day 1 every 3 weeks (21 days cycle)
Drug: Standard arm: Trabectedin in monotherapy
Trabectedin in monotherapy
Other Name: Trabectedin arm

Experimental: Experimental arm: Trabectedin + Olaparib
Trabectedin at the dose 1.1mg/m2 given as intravenous infusion at day 1 every 3 weeks (21 days cycle) plus Olaparib per os at the dose of 150 mg twice a day
Drug: Experimental arm: Trabectedin + Olaparib
Trabectedin given in combination to olaparib
Other Name: Trabectedin+ Olaparib arm

Primary Outcome Measures :
  1. Progression free Survival (PFS) [ Time Frame: At 6 months ]
    Survival without disease progression

Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: At 3 years ]
    Survival from the first dose treatment to death for any cause

  2. Overall Survival rate [ Time Frame: At 12 months ]
    Proportion of patients who are still alive at 12 months after have started the treatment

  3. Progression free Survival (PFS) [ Time Frame: At 3 years ]
    Survival without disease progression

  4. Progression free Survival Rate [ Time Frame: At 6 months ]
    Proportion of patients who did not progress at 6 months after have started the treatment

  5. Growth Modulation Index (GMI) [ Time Frame: Week 6, week 12, week 18, week 27, week 36 ]
    Ratio of time to progression with the nth line of therapy to the those with the n-1th line.

  6. Adverse events related to the treatment [ Time Frame: Week 3, week6, week 9, week 12, week 18, week 27, week 36 ]
    Safety in term of adverse event is evaluate from the firs treatment dose throughout the study according to CTCAE 5.0

  7. Quality of Life according the 30 questions European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC Quality of Life Questionnaire C30) [ Time Frame: Week 3, week6, week 9, week 12, week 18, week 27, week 36 ]
    Evaluation of the quality of life collected with EORTC Quality of Life Questionnaire C30

  8. Quality of Life according the questionnaire Euro Quality Of Life 5 Domains (EQ-5D) [ Time Frame: Week 3, week6, week 9, week 12, week 18, week 27, week 36 ]
    Evaluation of the quality of life collected with EQ-5D

  9. Over all Response Rate [ Time Frame: At week 18 ]
    Overall response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Provision of written informed consent prior to any study specific procedures.
  • Patients with histologically documented and not surgically resectable or metastatic STS that progressed after first- or further-line treatments for relapsing disease.
  • At least one previous line of anthracycline-containing chemotherapy for advanced disease or relapsed/progressed within six months of a previous treatment with an anthracycline-containing chemotherapy in the neo-adjuvant/adjuvant setting.
  • Central revision will be mandatory in order to enroll a patient. Central revision will assess both diagnosis and adequacy of tumor specimen (minimum requisite will be a formalin-fixed paraffin-embedded block of either a 16-gauge tru-cut biopsy or a non-necrotic surgical tumor specimen). The patient has to consent BReast CAncer genes 1 and 2 (BRCA1 and BRCA 2) evaluation in the interest of avoiding misleading interpretation of resulting data.
  • Measurable disease according Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Patients with an ECOG 2 are eligible if it depends solely on orthopedic problems.
  • Estimated life expectancy of at least 16 weeks.
  • Age ≥18 years.
  • Left Ventricular Ejection Fraction ≥ 50% and/or above lower institutional limit of normality
  • Adequate bone marrow, liver and renal function assessed within 7 days prior to
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1

Exclusion Criteria:

  • Previous enrolment in the present study
  • Participation in another clinical study with an investigational product during the last 4 weeks.
  • Previous treatment with trabectedin, olaparib or other Poly Adpribose polymerase 1 (PARP-1) inhibitors or analogue.
  • Persistent toxicities (≥ grade 2 according Common Terminology Criteria for Adverse Events - CTCAE) with the exception of alopecia, caused by previous anticancer therapies.
  • Dementia or significantly altered mental status (e.g., psychiatric disorder) that would prevent the understanding or rendering of informed consent and compliance with the requirements of this protocol.
  • Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months, serious uncontrolled cardiac arrhythmia, uncontrolled hyperlipidemia, active or uncontrolled severe infection, cirrhosis, chronic or persistent active hepatitis or severely impaired lung function. In particular for history of cardiac disease: congestive heart failure >New York Hearth Association (NYHA) class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for Human Immunodeficiency Virus (HIV).
  • Active clinically serious infections (> grade 2 CTCAE).
  • Active viral hepatitis [Hepatitis B Virus - (HBV) or Hepatitis C Virus (HCV) infection]
  • Metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, does not require corticosteroid treatment, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry). Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
  • Patients with seizure disorders requiring medication (such as steroids or anti-epileptics).
  • Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 28 days before the start of treatment. Pregnancy test will be repeated and confirmed on cycle 1 day 1 before treatment start. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 5 months after last dose of study drug.
  • Patients with evidence or history of bleeding diathesis.
  • Patients undergoing renal dialysis.
  • Patients unable to swallow oral medications.
  • Uncontrolled diabetes (fasting glucose > 2 x Upper Normal Limit).
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency). Topical or inhaled corticosteroids are permitted.
  • Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ , Stage 1, grade 1 endometrial carcinoma. Patients with a history of localised triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs).
  • Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry
  • Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed).
  • Major surgery within 4 weeks of start of study. Thus, patients must have recovered from wound or directly surgical related complications at time of study randomization.
  • Investigational drug therapy outside of this trial during or within 4 weeks of study entry.
  • Patients with known hypersensitivity to trabectedin, olaparib or to their excipients.
  • Patients can receive a stable dose of bisphosphonates for bone metastases before and during the study as long as these were started at least 4 weeks prior to treatment with the study drugs.
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  • A history of noncompliance to medical regimens or inability or unwillingness to return for scheduled visits.
  • Resting ElectroCardioGram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
  • Concomitant use of known strong CYtochromeP3A (CYP3A) inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study drugs is 2 weeks.
  • Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting study drugs is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation
  • Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of them

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 identifier (NCT number): NCT03838744

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Contact: Giovanni Giovanni, MD 0039-011-993 ext 3623

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Azienda Ospedaliero-Universitaria Di Bologna Active, not recruiting
Bologna, BO, Italy, 40139
I.R.S.T. di Meldola Recruiting
Meldola, FC, Italy
Contact: Lorena Gurreri, MD         
Principal Investigator: Lorena Gurreri         
Nuovo Ospedale di Prato Not yet recruiting
Prato, Firenze, Italy, 59100
Contact: Giacomo G. Baldi, MD    0039057443 ext 4766   
Principal Investigator: Giacomo G. Baldi, MD         
Fondazione IRCCS Istituto Nazionale dei Tumori Recruiting
Milano, MI, Italy, 20133
Contact: Roberta Sanfilippo, MD    39022390 ext 2804   
Principal Investigator: Roberta Sanfilippo, MD         
Istituto Europeo di Oncologia Recruiting
Milano, MI, Italy, 20141
Contact: Tommaso M. De Pas, MD    +390257489482   
Principal Investigator: Tommaso M. De Pas, MD         
Istituto Clinico Humanitas Not yet recruiting
Rozzano, MI, Italy, 20089
Contact: Alexia Bertuzzi, MD    +390282244540   
Principal Investigator: Alexia Bertuzzi, MD         
Azienda Ospedaliera Universitaria Paolo Giaccone Not yet recruiting
Palermo, PA, Italy, 90127
Contact: Giuseppe Badalamenti, MD    0039091655 ext 4513   
Contact: Badalamenti         
Principal Investigator: Giuseppe Badalamenti, MD         
Centro di Riferimento Oncologico di Aviano Recruiting
Aviano, PD, Italy, 33081
Contact: Angela Buonadonna, MD    +39 0434 659190   
Principal Investigator: Angela Buonadonna, MD         
Policlinico Universitario Campus Biomedico Recruiting
Roma, RM, Italy, 00128
Contact: Bruno Vincenzi, MD    +3902225411123   
Principal Investigator: Bruno Vincenzi, MD         
Fondazione del Piemonte per l'Oncologia IRCC Candiolo Recruiting
Candiolo, Torino, Italy, 10060
Contact: Giovanni Grignani, MD    0039-011-993 ext 3623   
Contact: Lorenzo D'Ambrosio, MD    0039-011-993 ext 3623   
Principal Investigator: Giovanni Grignani, MD         
Sub-Investigator: Lorenzo D'Ambrosio, MD         
Ospedale San Giovanni Bosco Not yet recruiting
Torino, TO, Italy
Contact: Alessandro Comandone, MD         
Principal Investigator: Alessandro Comandone, MD         
Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors Recruiting
Bologna, Italy, 40136
Contact: Anna Paioli, MD    +390516366199 ext 199   
Principal Investigator: Anna Paioli, MD         
Irccs Istituto Oncologico Veneto (Iov) Recruiting
Padova, Italy
Contact: Antonella Brunello, MD    0039049 8215 ext 910   
Principal Investigator: Antonella Brunello, MD         
Istituto Nazionale Tumori Regina Elena - Unit of Medical Oncology I Recruiting
Roma, Italy, 00144
Contact: Virginia Ferraresi, MD    +390652666 ext 773   
Contact: MD         
Principal Investigator: Virginia Ferraresi, MD         
Sponsors and Collaborators
Italian Sarcoma Group
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Principal Investigator: Giovanni Giovanni, MD Fondazione del Piemonte IRCCS di Candiolo

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Responsible Party: Italian Sarcoma Group Identifier: NCT03838744    
Other Study ID Numbers: ISG-TOMAS 2
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: November 1, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Italian Sarcoma Group:
Soft tissue sarcoma
Additional relevant MeSH terms:
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Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents