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

Sponsor

Italian Sarcoma Group (Other)

Overall Status

Recruiting

CT.gov ID

NCT03023124

Collaborator

(none)

Enrollment

Locations

Arms

71.9

Anticipated Duration (Months)

8.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Solitary Fibrous Tumors	Drug: Trabectedin Drug: Adriamycin Drug: Dacarbazine	Phase 2

Detailed 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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 4, 2018

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trabectedin trabectedin: 1.5 mg/m² - 1.3 mg/m² given in 24-hour continuous infusion every 21 days for 6 cycles	Drug: Trabectedin Treatment with trabectedin repeated every 21 days for 6 cycles
Experimental: Adriamycin and Dacarbazine Adriamycin: 75 mg/m2/day, bolus, day 1 every 21 days for 6 cycles Dacarbazine: 400 mg/m2/day, days 1, 2 every 21 days for 6 cycles	Drug: Adriamycin Treatment with Adriamycin at day 1 every 21 days for 6 cycles Drug: Dacarbazine Treatment with Dacarbazine at days 1 and 2 every 21 days for 6 cycles

Arm

Intervention/Treatment

Experimental: Trabectedin

trabectedin: 1.5 mg/m² - 1.3 mg/m² given in 24-hour continuous infusion every 21 days for 6 cycles

Drug: Trabectedin

Treatment with trabectedin repeated every 21 days for 6 cycles

Experimental: Adriamycin and Dacarbazine

Adriamycin: 75 mg/m2/day, bolus, day 1 every 21 days for 6 cycles Dacarbazine: 400 mg/m2/day, days 1, 2 every 21 days for 6 cycles

Drug: Adriamycin

Treatment with Adriamycin at day 1 every 21 days for 6 cycles

Drug: Dacarbazine

Treatment with Dacarbazine at days 1 and 2 every 21 days for 6 cycles

Outcome Measures

Primary Outcome Measures

Overall Tumor Response Rate [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.]
evaluate the activity of trabectedin and of adriamycin in combination with dacarbazine, according to Response Evaluation Criteria in Solid Tumor (RECIST), version 1.1

Secondary Outcome Measures

Choi Response Rate [week 6, week 12, week 18, then every 12 weeks up to 54 weeks]
Percentage of patient who experienced Complete or Partial Responses after treatment according to Choi Criteria.
Overall Survival (OS) [From enrollment up to 5 years]
Time from the date of enrollment to date of death
Progression Free Survival (PFS) [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]
Survival free of progressive disease evaluated from enrollment up to progression according to RECIST, or death
Clinical Benefit Rate (CBR) [week 6, week 12, week 18, then every 12 weeks up to 54 weeks]
Percentage of patients who have achieved complete response, partial response or stable disease ≥ 6 months
Response rate by RECIST after the cross over [week 18, week 24, week 30, week 36 and then every 12 weeks up to 54 weeks]
Percentage of patient who experienced Complete or Partial Responses according RECIST 1.1 after cross over
Progression Free Survival (PFS) after cross over up to progression according to RECIST, or death [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]
Survival free of progressive disease evaluated from
Safety according to Common Terminology Criteria for Adverse Events (CTCAE) [From enrollment every 3 weeks up to 54 weeks]
Safety profile of the treatment evaluated according to Common Terminology Criteria for Adverse Events version 4.03

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Age ≥18 years
Histological centrally and molecularly confirmed diagnosis of solitary fibrous tumor (inclusive of the last available tumor sample)
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
Measurable or evaluable disease with RECIST
Evidence of progression by RECIST during the 6 months before study entry
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.
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
Adequate bone marrow function
Adequate organ function
Cardiac ejection fraction ≥50% as measured by echocardiogram
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.
No history of arterial and/or venous thromboembolic event within the previous 12 months.

Exclusion Criteria:

Any prior treatment with cytotoxic chemotherapy
1 line of anticancer targeted agents
Previous treatment with any other investigational or not investigational agents within 14 days of first day of study drug dosing
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
Previous radiotherapy to 25 % of the bone marrow
Major surgery within 4 weeks prior to study entry
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
Pregnancy or breast feeding
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
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
Known history of human immunodeficiency virus infection
Active or chronic hepatitis B or C requiring treatment with antiviral therapy
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
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
Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
Expected non-compliance to medical regimens

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nuovo Ospedale di Prato	Prato	Firenze	Italy	59100
2	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	MI	Italy	20133
3	Policlinico Universitario Campus Biomedico	Roma	RM	Italy	00128
4	IRCCS Istituto ortopedico Rizzoli	Bologna		Italy	40136
5	Fondazione Del Piemonte Per L'Oncologia Ircc Di Candiolo -	Candiolo		Italy	10060
6	Ospedale Giaccone	Palermo		Italy