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

NCT03838744 | Completed Phase 2

• 1 other identifier: ISG-TOMAS 2
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 13

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.

Conditions

Advanced Soft Tissue Sarcoma

Keywords

Soft tissue sarcoma

Outcome Measures

Primary Outcomes (1)

• Progression free Survival (PFS)

  Survival without disease progression

  At 6 months

Secondary Outcomes (9)

• Overall Survival (OS)

  At 3 years

• Overall Survival rate

  At 12 months

• Progression free Survival (PFS)

  At 3 years

• Progression free Survival Rate

  At 6 months

• Growth Modulation Index (GMI)

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

Study Arms (2)

Standard arm: Trabectedin in monotherapy

ACTIVE COMPARATOR

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

Experimental arm: Trabectedin + Olaparib

EXPERIMENTAL

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

Interventions

Standard arm: Trabectedin in monotherapy DRUG

Trabectedin in monotherapy

Also known as: Trabectedin arm

Standard arm: Trabectedin in monotherapy

Experimental arm: Trabectedin + Olaparib DRUG

Trabectedin given in combination to olaparib

Also known as: Trabectedin+ Olaparib arm

Experimental arm: Trabectedin + Olaparib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Italian Sarcoma Group: lead
• PharmaMar: collaborator
• AstraZeneca: collaborator

Study Sites (13)

Azienda Ospedaliero-Universitaria Di Bologna

Bologna, BO, 40139, Italy

Location

I.R.S.T. di Meldola

Meldola, FC, Italy

Location

Nuovo Ospedale di Prato

Prato, Firenze, 59100, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, 20133, Italy

Location

Istituto Europeo di Oncologia

Milan, MI, 20141, Italy

Location

Azienda Ospedaliera Universitaria Paolo Giaccone

Palermo, PA, 90127, Italy

Location

Centro di Riferimento Oncologico di Aviano

Aviano, PD, 33081, Italy

Location

Policlinico Universitario Campus Biomedico

Roma, RM, 00128, Italy

Location

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, 10060, Italy

Location

Ospedale San Giovanni Bosco

Torino, TO, Italy

Location

Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

Bologna, 40136, Italy

Location

Irccs Istituto Oncologico Veneto (Iov)

Padua, Italy

Location

Istituto Nazionale Tumori Regina Elena - Unit of Medical Oncology I

Roma, 00144, Italy

Location

Related Publications (5)

• 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.

  PMID: 30217671 BACKGROUND

• 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.

  PMID: 23385197 BACKGROUND

• 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.

  PMID: 27617661 BACKGROUND

• 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.

  PMID: 28754483 BACKGROUND

• 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.

  PMID: 36110934 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

olaparib

Condition Hierarchy (Ancestors)

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

Study Officials

• Giovanni Giovanni, MD

  Fondazione del Piemonte IRCCS di Candiolo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Controlled, parallel, two arm study

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 12, 2019
• Study Start: May 20, 2020
• Primary Completion: November 29, 2024
• Study Completion: November 29, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (13)