- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02805725
Targeting Microenvironment and Cellular Immunity in Sarcomas Weekly Trabectedin Combined With Metronomic Cyclophosphamide (TARMIC)
Targeting Microenvironment and Cellular Immunity in Sarcomas Weekly Trabectedin Combined With Metronomic Cyclophosphamide (CP) in Patients With Advanced Pretreated Soft-tissue Sarcomas. A Phase I/II Study From the French Sarcoma Group.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Bordeaux, France, 33076
- Institut Bergonié
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with soft-tissue sarcoma histologically confirmed by central review
- Metastatic or unresectable locally advanced disease,
- Age ≥ 18 years,
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2,
- Life expectancy > 3 months,
- Measurable disease according to RECIST v1.1 outside any previously irradiated field,
- For patients included in phase II study, progressive disease according to RECIST v1.1 criteria diagnosed on the basis of two CT scan or MRI obtained at an interval less than 6 months in the period of 12 months prior to inclusion and confirmed by central review,
- Previous use of Anthracyclines,
- Have provided tissue from an archival tissue sample,
- At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
Adequate hematological, renal, metabolic and hepatic function:
- Hemoglobin ≥ 9 g/dl (patients may have received prior red blood cell [RBC] transfusion, if clinically indicated); absolute neutrophil count (ANC) ≥ 1.5 x 10^9/l, and platelet count ≥ 100 x 10^9/l
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST)< or = 2.5 x upper limit of normality (ULN) ( < or = 5 in case of extensive liver involvement) and alkaline phosphatase (AP) < or = 2.5 x ULN
- Total bilirubin < or = ULN.
- Albumin ≥ 25 g/l
- Serum Creatinine < or =1.5 x ULN or calculated creatinine clearance (CrCl) ≥ 30 ml/min (according to Cockroft formula).
- Creatine Phosphokinase (CPK) < or = 2.5 x ULN
- Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier,
- No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
- Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4.0),
- Patients with a French social security in compliance with the Law relating to biomedical research (Article 1121-11 of French Public Health Code),
- Voluntarily signed and dated written informed consent prior to any study specific procedure.
Exclusion Criteria:
- Previous treatment with Trabectedin,
- Currently active bacterial or fungus infection (> grade 2 CTC [CTCAE] HIV1, HIV2, hepatitis B or hepatitis C infections,
- History of chronic alcohol use and/or cirrhosis,
The following unstable cardiac conditions are not allowed:
- Congestive heart failure
- Angina pectoris
- Myocardial infarction within 1 year before registration
- Uncontrolled arterial hypertension defined as blood pressure ≥ 150/100 mmHg despite optimal medical therapy
- Arrhythmias clinically significant
- Patients unable to receive corticotherapy,
- Known central nervous system malignancy (CNS),
- Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding,
- Participation to a study involving a medical or therapeutic intervention in the last 30 days,
- Previous enrolment in the present study,
- Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
- Known hypersensitivity to any involved study drug or any of its formulation components.
- Recent vaccination (in the last 2 weeks before inclusion) for yellow fever.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1: Trabectedin 0.30 mg/m2 IV + CP
Trabectedin 0.30 mg/m2 will be administered intravenously (IV), 3-hour infusion weekly for three consecutive weeks (days 1, 8 and 15) every 4 weeks, in cohort 1 of dose escalation. Cyclophosphamide (CP) will be administered bi-daily (50 mg x 2), and given on a week on/week off schedule. 1 cycle = 28 days |
A treatment cycle consists of 4 weeks.
Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.) Cyclophosphamide will be administered bi-daily (50 mg x 2), and given on a week on/week off schedule.
Phase I trial based on a dose escalating study design (3+3 traditional design) assessing four dose levels of Trabectedin in combination with metronomic cyclophosphamide (CP). A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.) |
Experimental: Cohort 2: Trabectedin 0.40 mg/m2 IV + CP
Trabectedin 0.40 mg/m2 will be administered intravenously (IV), 3-hour infusion weekly for three consecutive weeks (days 1, 8 and 15) every 4 weeks, in cohort 2 of dose escalation. Cyclophosphamide (CP) will be administered bi-daily (50 mg x 2), and given on a week on/week off schedule. 1 cycle = 28 days |
A treatment cycle consists of 4 weeks.
Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.) Cyclophosphamide will be administered bi-daily (50 mg x 2), and given on a week on/week off schedule.
Phase I trial based on a dose escalating study design (3+3 traditional design) assessing four dose levels of Trabectedin in combination with metronomic cyclophosphamide (CP). A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.) |
Experimental: Cohort 3: Trabectedin 0.50 mg/m2 IV + CP
Trabectedin 0.50 mg/m2 will be administered intravenously (IV), 3-hour infusion weekly for three consecutive weeks (days 1, 8 and 15) every 4 weeks, in cohort 3 of dose escalation. Cyclophosphamide (CP) will be administered bi-daily (50 mg x 2), and given on a week on/week off schedule. 1 cycle = 28 days |
A treatment cycle consists of 4 weeks.
Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.) Cyclophosphamide will be administered bi-daily (50 mg x 2), and given on a week on/week off schedule.
Phase I trial based on a dose escalating study design (3+3 traditional design) assessing four dose levels of Trabectedin in combination with metronomic cyclophosphamide (CP). A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.) |
Experimental: Cohort 4: Trabectedin 0.60 mg/m2 IV + CP
Trabectedin 0.60 mg/m2 will be administered intravenously (IV), 3-hour infusion weekly for three consecutive weeks (days 1, 8 and 15) every 4 weeks, in cohort 4 of dose escalation. Cyclophosphamide (CP) will be administered bi-daily (50 mg x 2), and given on a week on/week off schedule. 1 cycle = 28 days |
A treatment cycle consists of 4 weeks.
Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.) Cyclophosphamide will be administered bi-daily (50 mg x 2), and given on a week on/week off schedule.
Phase I trial based on a dose escalating study design (3+3 traditional design) assessing four dose levels of Trabectedin in combination with metronomic cyclophosphamide (CP). A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.) |
Experimental: Phase II: Trabectedin 0.50 mg/m2 IV + CP
Trabectedin 0.50 mg/m2 will be administered intravenously (IV), 3-hour infusion weekly for three consecutive weeks (days 1, 8 and 15) every 4 weeks, in the phase II part of the study. Cyclophosphamide (CP) will be administered bi-daily (50 mg x 2), and given on a week on/week off schedule. 1 cycle = 28 days |
All patients will be treated with metronomic cyclophosphamide with the same schedule as in the phase I trial.
Patients will be included in a single-arm phase II trial. Administrated dose will be the RP2D defined in the dose escalation part of the trial. The design will follow a two-stage Simon's optimal design. All patients will be treated at the RP2D of trabectedin defined in the preliminary phase I trial with the same schedule as in the phase I trial. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: Maximum Tolerated Dose (MTD) of Trabectedin When Administered in Association With CP.
Time Frame: During the first cycle (28 days)
|
MTD was determined by testing increasing doses of trabectedin up to 0.60 mg/m2 via IV on dose escalation cohorts 1 to 4 with 3 to 6 participants each.The MTD is defined as the highest dose at which no more than 1 in 6 of the patients in the cohort experienced a DLT in the first treatment cycle.
See subsequent primary outcome measure for the DLT definition.
|
During the first cycle (28 days)
|
Phase I: Number of Patients Who Experienced Dose-Limiting Toxicities (DLTs)
Time Frame: During the first cycle (28 days)
|
A DLT was defined as a treatment-related (at least possibly related) adverse event using the CTCAE V4.0, occuring during the fist cycle of treatment (28 days), that meets one of the following criteria:
|
During the first cycle (28 days)
|
Phase II: Percentage of Patients in Non-progression at 6 Months (RECIST V1.1)
Time Frame: Phase II : 6 months after the start of treatment
|
Non-progression is defined as complete or partial response (CR, PR) or stable disease (SD), as per RECIST v1.1.
According to RECIST v1.1: Complete Response (CR) is defined as disappearance of all target lesions; Partial Response (PR) is defined as a >=30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at baseline (SSD); Stable disease (SD) is defined as Neither sufficient shrinkage (compared to baseline) to qualify for PR or CR nor sufficient increase (taking as reference the SSD or while on study, whichever is smallest) to qualify for progressive disease (PD).
|
Phase II : 6 months after the start of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: Percentage of Patients With Objective Response (RECIST V1.1)
Time Frame: Throughout the treatment period, an average of 6 months
|
Objective response is defined as complete or partial response (CR, PR) as per RECIST v1.1.
According to RECIST v1.1: Complete Response (CR) is defined as disappearance of all target lesions; Partial Response (PR) is defined as a >=30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at baseline (SSD).
|
Throughout the treatment period, an average of 6 months
|
Phase II: Median Overall Survival
Time Frame: From start of treatment, and during treatment until death for any cause for up to 12 months.
|
Overall survival is defined as the time from the study initiation to death (any cause).
Median overall survival was reported using kaplan-Meier method for calculation.
|
From start of treatment, and during treatment until death for any cause for up to 12 months.
|
Phase II: Median Profression-free Survival
Time Frame: From start of treatment, and during treatment until progression or death for any cause for up to 12 months.
|
Progression-free survival is defined as the time from study treatment initiation to disease progression or death (of any cause), whichever occurs first.
Progression is defined using RECIST v1.1, as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
Median PFS was reported using kaplan-Meier method for calculation.
|
From start of treatment, and during treatment until progression or death for any cause for up to 12 months.
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Sarcoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Trabectedin
Other Study ID Numbers
- IB 2015-04
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Soft-tissue Sarcomas
-
Grupo Espanol de Investigacion en SarcomasRecruitingAdvanced Solid Tumor | Advanced Soft-tissue Sarcoma | Advanced L-sarcomas | Other Advanced Sarcomas | Localized Soft-tissue SarcomaSpain
-
Henan Cancer HospitalCompleted
-
University of FloridaWithdrawnSoft Tissue Sarcomas
-
The Netherlands Cancer InstituteLeiden University Medical CenterRecruitingSoft Tissue SarcomasNetherlands
-
Vanderbilt-Ingram Cancer CenterRecruitingSoft Tissue SarcomasUnited States
-
Institut BergoniéMinistry of Health, France; National Cancer Institute, FranceRecruiting
-
NYU Langone HealthBristol-Myers SquibbWithdrawnSoft Tissue SarcomasUnited States
-
National Cancer Institute (NCI)CompletedRefractory Soft Tissue SarcomasUnited States
-
The Netherlands Cancer InstituteRoyal Marsden NHS Foundation TrustTerminatedSarcoma | Soft Tissue SarcomasUnited Kingdom, Netherlands
-
Merck Sharp & Dohme LLCAriad PharmaceuticalsCompletedMetastatic Soft-Tissue Sarcomas | Metastatic Bone Sarcomas
Clinical Trials on Phase 1: Cyclophosphamide
-
Janssen Research & Development, LLCCompletedRelapsed or Refractory Hodgkin LymphomaFrance, Germany
-
Duke UniversityNational Institute of Mental Health (NIMH)Completed
-
University of North Carolina, Chapel HillNational Institute on Drug Abuse (NIDA)CompletedOpioid Abuse (Disorder)United States
-
Shenzhen Precision Health Food Technology Co. Ltd...CompletedDiabetes | Sugar; Blood, HighChina
-
Brigham and Women's HospitalWithdrawn
-
University of MinnesotaArizona State UniversityCompleted
-
enGene, Inc.RecruitingSuperficial Bladder Cancer | Non-muscle Invasive Bladder Cancer With Carcinoma in SituUnited States
-
University of California, DavisNational Institute of Mental Health (NIMH)TerminatedPsychotic DisordersUnited States
-
Hospices Civils de LyonCompletedHereditary Hemorrhagic TelangiectasiaFrance