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Advanced Soft Tissue SarcomaPhase 2TOMAS2NCT03838744

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

A Phase 2 study testing Standard arm: Trabectedin in monotherapy and Experimental arm: Trabectedin + Olaparib in people with Advanced Soft Tissue Sarcoma, run by Italian Sarcoma Group at 13 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. 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?
Standard arm: Trabectedin in monotherapy and Experimental arm: Trabectedin + Olaparib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
13 sitesItaly
Study dates
20 May 2020to 29 Nov 2024
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

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

Italy13 sites

  • Centro di Riferimento Oncologico di Aviano

    Aviano, PD, 33081

  • Azienda Ospedaliero-Universitaria Di Bologna

    Bologna, BO, 40139

  • Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

    Bologna, 40136

  • Fondazione del Piemonte per l'Oncologia IRCC Candiolo

    Candiolo, Torino, 10060

  • I.R.S.T. di Meldola

    Meldola, FC

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, MI, 20133

  • Istituto Europeo di Oncologia

    Milan, MI, 20141

  • Irccs Istituto Oncologico Veneto (Iov)

    Padova

  • Azienda Ospedaliera Universitaria Paolo Giaccone

    Palermo, PA, 90127

  • Nuovo Ospedale di Prato

    Prato, Firenze, 59100

  • Policlinico Universitario Campus Biomedico

    Roma, RM, 00128

  • Istituto Nazionale Tumori Regina Elena - Unit of Medical Oncology I

    Roma, 00144

  • Ospedale San Giovanni Bosco

    Torino, TO

Other trials in Italy

About this study

Official title: Phase 2 Randomized Trial of Trabectedin + Olaparib vs. Trabectedin in Advanced, Metastatic or Unresectable Soft Tissue Sarcoma After Failure of Standard Treatments.

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.

Read the 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.

Being tested
Standard arm: Trabectedin in monotherapy, Experimental arm: Trabectedin + Olaparib
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.

  • Standard arm: Trabectedin in monotherapyDrug

    Also called Trabectedin arm

    Trabectedin in monotherapy

  • Experimental arm: Trabectedin + OlaparibDrug

    Also called Trabectedin+ Olaparib arm

    Trabectedin given in combination to olaparib

Study groups in NCT03838744
Study groupRoleWhat they receive
Standard arm: Trabectedin in monotherapyActive comparatorTrabectedin 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)
Receives: Drug: Standard arm: Trabectedin in monotherapy
Experimental arm: Trabectedin + OlaparibExperimentalTrabectedin 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
Receives: Drug: Experimental arm: Trabectedin + Olaparib

What is being measured

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

  1. Progression free Survival (PFS)

    Survival without disease progression

    Measured: At 6 months

Secondary outcomes (9)

  1. Overall Survival (OS)

    Survival from the first dose treatment to death for any cause

    Measured: At 3 years

  2. Overall Survival rate

    Proportion of patients who are still alive at 12 months after have started the treatment

    Measured: At 12 months

  3. Progression free Survival (PFS)

    Survival without disease progression

    Measured: At 3 years

  4. Progression free Survival Rate

    Proportion of patients who did not progress at 6 months after have started the treatment

    Measured: At 6 months

  5. Growth Modulation Index (GMI)

    Ratio of time to progression with the nth line of therapy to the those with the n-1th line.

    Measured: Week 6, week 12, week 18, week 27, week 36

  6. Adverse events related to the treatment

    Safety in term of adverse event is evaluate from the firs treatment dose throughout the study according to CTCAE 5.0

    Measured: Week 3, week6, week 9, week 12, week 18, week 27, week 36

  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)

    Evaluation of the quality of life collected with EORTC Quality of Life Questionnaire C30

    Measured: Week 3, week6, week 9, week 12, week 18, week 27, week 36

  8. Quality of Life according the questionnaire Euro Quality Of Life 5 Domains (EQ-5D)

    Evaluation of the quality of life collected with EQ-5D

    Measured: Week 3, week6, week 9, week 12, week 18, week 27, week 36

  9. Over all Response Rate

    Overall response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Measured: At week 18

Timeline

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

  1. First posted12 Feb 2019
  2. Study start20 May 2020
  3. Primary completion29 Nov 2024
  4. Study completion29 Nov 2024

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
Model description
Controlled, parallel, two arm study
Masking
None (open label)
Enrolment
130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03838744
Sponsor's protocol ID
ISG-TOMAS 2
Acronym
TOMAS2
Status last verified
Nov 2024
First submitted
11 Feb 2019
Last updated
4 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Grignani G, D'Ambrosio L, Pignochino Y, Palmerini E, Zucchetti M, Boccone P, Aliberti S, Stacchiotti S, Bertulli R, Piana R, Miano S, Tolomeo F, Chiabotto G, Sangiolo D, Pisacane A, Dei Tos AP, Novara L, Bartolini A, Marchesi E, D'Incalci M, Bardelli A, Picci P, Ferrari S, Aglietta M. Trabectedin and olaparib in patients with advanced and non-resectable bone and soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian Sarcoma Group. Lancet Oncol. 2018 Oct;19(10):1360-1371. doi: 10.1016/S1470-2045(18)30438-8. Epub 2018 Sep 11.

    PubMed 30217671

  • Samuels BL, Chawla S, Patel S, von Mehren M, Hamm J, Kaiser PE, Schuetze S, Li J, Aymes A, Demetri GD. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol. 2013 Jun;24(6):1703-9. doi: 10.1093/annonc/mds659. Epub 2013 Feb 5.

    PubMed 23385197

  • Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. doi: 10.1016/S1470-2045(16)30376-X. Epub 2016 Sep 9.

    PubMed 27617661

  • Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25.

    PubMed 28754483

  • Merlini A, Centomo ML, Ferrero G, Chiabotto G, Miglio U, Berrino E, Giordano G, Brusco S, Pisacane A, Maldi E, Sarotto I, Capozzi F, Lano C, Isella C, Crisafulli G, Aglietta M, Dei Tos AP, Sbaraglia M, Sangiolo D, D'Ambrosio L, Bardelli A, Pignochino Y, Grignani G. DNA damage response and repair genes in advanced bone and soft tissue sarcomas: An 8-gene signature as a candidate predictive biomarker of response to trabectedin and olaparib combination. Front Oncol. 2022 Aug 30;12:844250. doi: 10.3389/fonc.2022.844250. eCollection 2022.

    PubMed 36110934

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Standard arm: Trabectedin in monotherapy and Experimental arm: Trabectedin + Olaparib in people with Advanced Soft Tissue Sarcoma, run by Italian Sarcoma Group at 13 sites in Italy.

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 11 inclusion and 32 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: finished, as of the sponsor's last update on 4 Dec 2024. 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 Italy. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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: At 6 months). 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 NCT03838744, which also lists 5 linked publications.

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 4 Dec 2024.

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