Study With Trabectedin Versus Adriamycin Plus Dacarbazine, in Patients With Advanced Solitary Fibrous Tumor

Solitary Fibrous Tumors Clinical Trial

— STRADA  

Official title:

Solitary Fibrous Tumor: Phase II Study on Trabectedin Versus Adriamycin Plus Dacarbazine in Advanced Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03023124
• Other study ID #: ISG STRADA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 4, 2018
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: Italian Sarcoma Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase II randomized study for the comparison of trabectedin versus doxorubicin plus dacarbazine in patients with advanced solitary fibrous tumor

Description:

Patients with solitary fibrous tumor will be randomized to receive 6 cycles of trabectedin or doxorubicin plus dacarbazine. In case of progression or unacceptable toxicity while under the experimental treatment prior to the completion of the 6 cycles, the patients will be offered to cross to the other arm (trabectedin arm to doxorubicin plus dacarbazine arm and vice versa).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 23
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. The patient or legal representative must be able to read and understand the informed consent form (ICF) and must have been willing to give written informed consent and any locally required authorisation before any study-specific procedures, including screening evaluations, sampling, and analyses.

2. Age =18 years

3. Histological centrally and molecularly confirmed diagnosis of solitary fibrous tumor (inclusive of the last available tumor sample)

4. Locally advanced disease (i.e. surgical resection of local disease unfeasible radically, or unaccepted by the patient, or amenable to become less demolitive, or feasible, or easier, after cytoreduction) and/or metastatic disease

5. Measurable or evaluable disease with RECIST

6. Evidence of progression by RECIST during the 6 months before study entry

7. Patients must be cytotoxic chemotherapy naïve (patients treated with neoadjuvant/adjuvant chemotherapy cannot be included) or could have received a previous target agent in front-line setting.

8. Eastern Cooperative Oncology Group (ECOG) Performance Status = 2

9. Adequate bone marrow function

10. Adequate organ function

11. Cardiac ejection fraction =50% as measured by echocardiogram

12. Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study.

13. No history of arterial and/or venous thromboembolic event within the previous 12 months.

Exclusion Criteria:

1. Any prior treatment with cytotoxic chemotherapy

2. >1 line of anticancer targeted agents

3. Previous treatment with any other investigational or not investigational agents within 14 days of first day of study drug dosing

4. Previous treatment with radiation therapy within 14 days of first day of study drug dosing, or patients who have not recovered from adverse events due to agents previously administered

5. Previous radiotherapy to 25 % of the bone marrow

6. Major surgery within 4 weeks prior to study entry

7. Other primary malignancy with <5 years clinically assessed disease-free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged to entail a low risk of relapse

8. Pregnancy or breast feeding

9. Cardiovascular diseases resulting in a New York Heart Association Functional Status >2 (24). Medical history of a myocardial infarction < 6 months prior to initiation of study treatment

10. Medical history of arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment

11. Known history of human immunodeficiency virus infection

12. Active or chronic hepatitis B or C requiring treatment with antiviral therapy

13. Medical history of hemorrhage or a bleeding event = Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment

14. Evidence of any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results

15. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs

16. Expected non-compliance to medical regimens

Related Conditions & MeSH terms

• Hemangiopericytoma
• Solitary Fibrous Tumors

Intervention

Drug:
• Trabectedin
Treatment with trabectedin repeated every 21 days for 6 cycles
• Adriamycin
Treatment with Adriamycin at day 1 every 21 days for 6 cycles
• Dacarbazine
Treatment with Dacarbazine at days 1 and 2 every 21 days for 6 cycles

Locations

Country	Name	City	State
Italy	IRCCS Istituto ortopedico Rizzoli	Bologna
Italy	Fondazione Del Piemonte Per L'Oncologia Ircc Di Candiolo -	Candiolo
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	MI
Italy	Ospedale Giaccone	Palermo
Italy	Nuovo Ospedale di Prato	Prato	Firenze
Italy	Policlinico Universitario Campus Biomedico	Roma	RM

Sponsors (1)

Lead Sponsor	Collaborator
Italian Sarcoma Group

Country where clinical trial is conducted

Italy, 

References & Publications (12)

Beadle GF, Hillcoat BL. Treatment of advanced malignant hemangiopericytoma with combination adriamycin and DTIC: a report of four cases. J Surg Oncol. 1983 Mar;22(3):167-70. doi: 10.1002/jso.2930220306. — View Citation

Chaigneau L, Kalbacher E, Thiery-Vuillemin A, Fagnoni-Legat C, Isambert N, Aherfi L, Pauchot J, Delroeux D, Servagi-Vernat S, Mansi L, Pivot X. Efficacy of trabectedin in metastatic solitary fibrous tumor. Rare Tumors. 2011 Jul 11;3(3):e29. doi: 10.4081/rt.2011.e29. Epub 2011 Jul 18. — View Citation

Dagrada GP, Spagnuolo RD, Mauro V, Tamborini E, Cesana L, Gronchi A, Stacchiotti S, Pierotti MA, Negri T, Pilotti S. Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation. Mod Pathol. 2015 Aug;28(8):1074-83. doi: 10.1038/modpathol.2015.70. Epub 2015 May 29. — View Citation

Domont J, Massard C, Lassau N, Armand JP, Le Cesne A, Soria JC. Hemangiopericytoma and antiangiogenic therapy: clinical benefit of antiangiogenic therapy (sorafenib and sunitinib) in relapsed malignant haemangioperyctoma /solitary fibrous tumour. Invest New Drugs. 2010 Apr;28(2):199-202. doi: 10.1007/s10637-009-9249-1. Epub 2009 Apr 8. No abstract available. — View Citation

Khalifa J, Ouali M, Chaltiel L, Le Guellec S, Le Cesne A, Blay JY, Cousin P, Chaigneau L, Bompas E, Piperno-Neumann S, Bui-Nguyen B, Rios M, Delord JP, Penel N, Chevreau C. Efficacy of trabectedin in malignant solitary fibrous tumors: a retrospective analysis from the French Sarcoma Group. BMC Cancer. 2015 Oct 15;15:700. doi: 10.1186/s12885-015-1697-8. — View Citation

Martin-Broto J, Pousa AL, de Las Penas R, Garcia Del Muro X, Gutierrez A, Martinez-Trufero J, Cruz J, Alvarez R, Cubedo R, Redondo A, Maurel J, Carrasco JA, Lopez-Martin JA, Sala A, Meana JA, Ramos R, Martinez-Serra J, Lopez-Guerrero JA, Sevilla I, Balana C, Vaz A, De Juan A, Alemany R, Poveda A. Randomized Phase II Study of Trabectedin and Doxorubicin Compared With Doxorubicin Alone as First-Line Treatment in Patients With Advanced Soft Tissue Sarcomas: A Spanish Group for Research on Sarcoma Study. J Clin Oncol. 2016 Jul 1;34(19):2294-302. doi: 10.1200/JCO.2015.65.3329. Epub 2016 May 16. — View Citation

Park MS, Patel SR, Ludwig JA, Trent JC, Conrad CA, Lazar AJ, Wang WL, Boonsirikamchai P, Choi H, Wang X, Benjamin RS, Araujo DM. Activity of temozolomide and bevacizumab in the treatment of locally advanced, recurrent, and metastatic hemangiopericytoma and malignant solitary fibrous tumor. Cancer. 2011 Nov 1;117(21):4939-47. doi: 10.1002/cncr.26098. Epub 2011 Apr 8. — View Citation

Park MS, Ravi V, Conley A, Patel SR, Trent JC, Lev DC, Lazar AJ, Wang WL, Benjamin RS, Araujo DM. The role of chemotherapy in advanced solitary fibrous tumors: a retrospective analysis. Clin Sarcoma Res. 2013 May 11;3(1):7. doi: 10.1186/2045-3329-3-7. — View Citation

Stacchiotti S, Libertini M, Negri T, Palassini E, Gronchi A, Fatigoni S, Poletti P, Vincenzi B, Dei Tos AP, Mariani L, Pilotti S, Casali PG. Response to chemotherapy of solitary fibrous tumour: a retrospective study. Eur J Cancer. 2013 Jul;49(10):2376-83. doi: 10.1016/j.ejca.2013.03.017. Epub 2013 Apr 6. — View Citation

Stacchiotti S, Tortoreto M, Baldi GG, Grignani G, Toss A, Badalamenti G, Cominetti D, Morosi C, Dei Tos AP, Festinese F, Fumagalli E, Provenzano S, Gronchi A, Pennacchioli E, Negri T, Dagrada GP, Spagnuolo RD, Pilotti S, Casali PG, Zaffaroni N. Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour. Eur J Cancer. 2014 Nov;50(17):3021-8. doi: 10.1016/j.ejca.2014.09.004. Epub 2014 Sep 27. — View Citation

Stacchiotti S, Tortoreto M, Bozzi F, Tamborini E, Morosi C, Messina A, Libertini M, Palassini E, Cominetti D, Negri T, Gronchi A, Pilotti S, Zaffaroni N, Casali PG. Dacarbazine in solitary fibrous tumor: a case series analysis and preclinical evidence vis-a-vis temozolomide and antiangiogenics. Clin Cancer Res. 2013 Sep 15;19(18):5192-201. doi: 10.1158/1078-0432.CCR-13-0776. Epub 2013 Jul 25. — View Citation

Valentin T, Fournier C, Penel N, Bompas E, Chaigneau L, Isambert N, Chevreau C. Sorafenib in patients with progressive malignant solitary fibrous tumors: a subgroup analysis from a phase II study of the French Sarcoma Group (GSF/GETO). Invest New Drugs. 2013 Dec;31(6):1626-7. doi: 10.1007/s10637-013-0023-z. Epub 2013 Sep 5. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Tumor Response Rate	evaluate the activity of trabectedin and of adriamycin in combination with dacarbazine, according to Response Evaluation Criteria in Solid Tumor (RECIST), version 1.1	From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first assessed up to 54 weeks.
Secondary	Choi Response Rate	Percentage of patient who experienced Complete or Partial Responses after treatment according to Choi Criteria.	week 6, week 12, week 18, then every 12 weeks up to 54 weeks
Secondary	Overall Survival (OS)	Time from the date of enrollment to date of death	From enrollment up to 5 years
Secondary	Progression Free Survival (PFS)	Survival free of progressive disease evaluated from enrollment up to progression according to RECIST, or death	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks
Secondary	Clinical Benefit Rate (CBR)	Percentage of patients who have achieved complete response, partial response or stable disease = 6 months	week 6, week 12, week 18, then every 12 weeks up to 54 weeks
Secondary	Response rate by RECIST after the cross over	Percentage of patient who experienced Complete or Partial Responses according RECIST 1.1 after cross over	week 18, week 24, week 30, week 36 and then every 12 weeks up to 54 weeks
Secondary	Progression Free Survival (PFS) after cross over up to progression according to RECIST, or death	Survival free of progressive disease evaluated from	From date of cross over until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks
Secondary	Safety according to Common Terminology Criteria for Adverse Events (CTCAE)	Safety profile of the treatment evaluated according to Common Terminology Criteria for Adverse Events version 4.03	From enrollment every 3 weeks up to 54 weeks