| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma |
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| E.1.1.1 | Medical condition in easily understood language |
| Tumor formed from the soft tissues which tumor cells have migrated in other parts of the body or has grown into the neighbor tissues or cannot be removed with surgery |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10041298 |
| E.1.2 | Term | Soft tissue sarcomas histology unspecified |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to determine the preliminary efficacy of administration of INNO-206 compared to doxorubicin in subjects with metastatic, locally advanced, or unresectable soft tissue sarcoma as measured by progression-free survival, progression-free survival at 4 and 6 months, tumor response and overall survival. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective of this study is to evaluate the safety of INNO-206 compared to doxorubicin in this population assessed by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs, multiple-gated acquisition (MUGA) scans/cardiac ultrasound evaluations, electrocardiogram (ECG) results, and weight. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Age between 15-80 years (US only), and 18-80 (rest of world (ROW)), male or female.
2.Adjuvant or neoadjuvant chemotherapy (including doxorubicin) allowed if no tumor recurrence for at least 12 months since the last measurement, beginning or end of last chemotherapy.
3.Histologically or cytologically confirmed, locally advanced, unresectable, and/or metastatic soft tissue sarcoma of intermediate or high grade.
4.Capable of providing informed consent and complying with trial procedures.
5.ECOG performance status 0-2.
6.Life expectancy >12 weeks.
7.Measurable tumor lesions according to RECIST 1.1 criteria.
8.Women must not be able to become pregnant (eg post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. (Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.)
9.Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
10.Geographic accessibility to the site that ensures the subject will be able to keep all study-related appointments.
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| E.4 | Principal exclusion criteria |
1.Prior chemotherapy unless for adjuvant or neoadjuvant therapy with no tumor recurrence for at least 12 months.
2.Prior exposure to >3 cycles or 225 mg/m2 of doxorubicin or Doxil®.
3.Palliative surgery and/or radiation treatment less than 4 weeks prior to Randomization.
4.Exposure to any investigational agent within 30 days of Randomization.
5.Current Stage 1 or 2 soft tissue sarcomas.
6.Current evidence/diagnosis of alveolar soft part sarcoma, chondrosarcoma, rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumor (GIST), dermatofibrosarcoma, Ewing’s sarcoma, Kaposi’s sarcoma, mixed mesodermal tumor, clear cell sarcomas and unresectable low grade liposarcomas.
7.Central nervous system metastasis
8.History of other malignancies except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix unless documented free of cancer for >5 years.
9.Laboratory values: Screening serum creatinine >1.5xULN, alanine aminotransferase (ALT) > 3×ULN, or >5×ULN if liver metastases are present, total bilirubin >3×ULN, absolute neutrophil count <1,500/mm3, platelet concentration <100,000/mm3, hematocrit level <25% for females or <27% for males, coagulation tests (PT, PTT, INR) >1.5×ULN, and albumin <2.0 g/dL.
10.Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines.
11.Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
12.Baseline QTc >470 msec and/or previous history of QT prolongation while taking other medications. Concomitant use of medications associated with a high incidence of QT prolongation is not allowed
13.History or signs of active coronary artery disease with or without angina pectoris.
14.Serious myocardial dysfunction defined as scintigraphically (eg MUGA, myocardial scintigram) or ultrasound determined absolute left ventricular ejection fraction (LVEF) <45% of predicted.
15.History of HIV infection.
16.Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
17.Major surgery within 3 weeks prior to Randomization.
18.Substance abuse or any condition that might interfere with the subject’s participation in the study or in the evaluation of the study results.
19.Any condition that is unstable and could jeopardize the subject’s participation in the study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Tumor response will be monitored every 6 weeks from Cycle 1-Day 1 during treatment, at End of Treatment, 2 months following the End of Treatment scan (for those subjects completing 6 cycles), and then every 3 months until disease progression using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Tumor Response will be monitored every 60 days (2 months) after 6 weeks from Cycle 1-Day 1 until Day 240 (8 months during treatment, at end of treatment, 2 months following the End of Treatment scan, then every 3 months to disease progression. |
|
| E.5.2 | Secondary end point(s) |
1)To evaluate the overall survival, progression-free survival at 4 and 6 months, and objective overall response rate (ORR; RECIST 1.1 criteria, Study Reference Manual) in subjects with metastatic, locally advanced, or unresectable soft tissue sarcomas.
2)To evaluate the treatment-related toxicities in this subject population.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Tumor response will be monitored every 6 weeks from Cycle 1-Day 1 during treatment, at End of Treatment, 2 months following the End of Treatment scan (for those subjects completing 6 cycles), and then every 3 months until disease progression using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
2) at every visit |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Hungary |
| India |
| Romania |
| Russian Federation |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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