Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2013-003638-33 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| PharmaMar | INDUSTRY |
| AstraZeneca | INDUSTRY |
| Istituto Di Ricerche Farmacologiche Mario Negri | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a Phase 1b, multi-site, open-label, non-randomized clinical trial evaluating the safety, tolerability, and pharmacokinetics of escalating doses of olaparib and trabectedin in patients with unresectable advanced/metastatic sarcomas. Patients will continue to be treated on this combination regimen in the absence of disease progression, intolerable toxicity or patient's decision.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Trabectedin plus olaparib | Experimental | All patients will be treated with trabectedin and olaparib in an open-label fashion. The dosage of the drugs at which each patient is treated depends on the dose level reached at the time of enrollment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| trabectedin | Drug | trabectedin will be administered in a 24-h continuous i.v. infusion every 3 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| maximum tolerated dose | safety will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 | from start up to 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response | best overall response will be defined according to the Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST v 1.1) | baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years |
| Clinical Benefit Rate |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Giovanni Grignani, MD | Italian Sarcoma Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fondazione del Piemonte per l'Oncologia IRCC Candiolo | Candiolo | Torino | 10060 | Italy | ||
| Istituti Ortopedici Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30217671 | Result | 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. | |
| 33927108 |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012509 | Sarcoma |
| D001859 | Bone Neoplasms |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009371 | Neoplasms by Site |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077606 | Trabectedin |
| C531550 | olaparib |
| ID | Term |
|---|---|
| D004149 | Dioxoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D044005 | Tetrahydroisoquinolines |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| olaparib | Drug | olaparib will be administered in a continuous daily dose every 12 hours |
|
|
Clinical Benefit Rate (CBR): will be defined as the rate of CR (complete response) + PR (partial response) + stable disease lasting at least 12 weeks. CR, PR and stable disease will be defined according to RECIST v 1.1.
| baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years |
| Growth Modulation Index | Growth modulation index (GMI) will be calculated as: GMI=TTPn/TTPn-1. TTPn: Time To Progression on the new agent. TTP n-1: Time To Progression on the treatment the patient received just before the new agent was started. | baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years |
| Overall Survival | time from the date of enrollment to date of death or to the date being censored at two years (whichever occurs first). | baseline and up to 2 years |
| Duration of Tumor Response | Duration of Objective Response (complete or partial responses) will be measured from the date that a complete or partial response is first documented (whichever occurs first) to date of progression or death due to progressive disease, whichever occurs first. | baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years |
| Progression-Free Survival (PFS) | PFS is defined as the time from the date of enrollment to the date of first documentation of disease progression, or to the death from any cause. | baseline and every 2 cycles (6 weeks +/- 1 week) up to 2 years |
| Pharmacokinetic of trabectedin (AUC) | The concentration-time data will be used for a preliminary assessment of the effect of combination therapy on the single-dose pharmacokinetics of trabectedin and olaparib. The data will be analyzed by noncompartmental methods. Pharmacokinetic parameters for trabectedin: steady state profile, end of infusion concentration, area under the concentration-time curve (AUC), and, if data permit, terminal phase half-life. For these parameters, the following descriptive statistics will be calculated: mean, standard deviation, coefficient of variation, median, and geometric mean. Any drug-drug interaction will be thoroughly searched. For both trabectedin and olaparib all pharmacokinetic evaluations will be done only for the first 2 cycles. | baseline, days 1-2-3-4-5-8-15 of the first two cycles |
| Pharmacokinetic of olaparib (steady state profile and so maximum concentration, minimal concentration, and AUC will be calculated) | The concentration-time data will be used for a preliminary assessment of the effect of combination therapy on the single-dose pharmacokinetics of trabectedin and olaparib. The data will be analyzed by noncompartmental methods. The following pharmacokinetic parameter values will be obtained for olaparib: steady state profile and so maximum concentration, minimal concentration, and AUC will be calculated. For these parameters, the following descriptive statistics will be calculated: mean, standard deviation, coefficient of variation, median, and geometric mean. Any drug-drug interaction will be thoroughly searched. For both trabectedin and olaparib all pharmacokinetic evaluations will be done only for the first 2 cycles. | baseline, day -5 cycle 1, day 1 cycle 2, of the first two cycles |
| safety evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 | safety will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 | baseline up to 28 days after last dose of study treatment up to 2 years |
| Biomarkers (composite outcome) | Several gene assessments (expression, amplification/ deletion, single nucleotide polymorphisms) on DNA-damage response-related markers (including but not limited to BRCA 1-2, ERCC 1-2-5, XRCC 1-2-3, RAD51 and 53BP1, PARP 1-2, P-histone H2AX and others) will be conducted. Statistical analysis will be performed to investigate the association between trial outcomes and polymorphisms of these genes. | baseline, day 1-2-8-15 of each cycle up to 2 years |
| Bologna |
| 40136 |
| Italy |
| Istituto Nazionale Tumori - Unit of Medical Oncology | Milan | 20133 | Italy |
| Derived |
| Vyse S, Thway K, Huang PH, Jones RL. Next-generation sequencing for the management of sarcomas with no known driver mutations. Curr Opin Oncol. 2021 Jul 1;33(4):315-322. doi: 10.1097/CCO.0000000000000741. |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D007546 |
| Isoquinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |