| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Soft Tissue Sarcoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Metastatic Soft Tissue Sarcoma is a type of cancer that originates in soft tissue, such as fat and muscle, and has spread to other parts of the body. |
|
| 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 | 15.1 |
| E.1.2 | Level | HLGT |
| E.1.2 | Classification code | 10041299 |
| E.1.2 | Term | Soft tissue sarcomas |
| 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 |
To evaluate the radiologic progression-free survival (PFS) of subjects treated with the combination of gemcitabine/docetaxel (G/D) plus MORAb-004 versus G/D plus placebo in subjects with metastatic soft tissue sarcoma (mSTS) in 4 defined subgroups:
1. Liposarcoma (excluding pure, well-differentiated sarcoma)
2. Leiomyosarcoma
3. Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (UPS previously characterized as MFH)
4. Other STS, i.e., subjects with a histologic diagnosis of high grade sarcoma not otherwise specified (NOS), angiosarcoma, synovial sarcoma, rhabdomyosarcoma, hemagiopericytoma/ solitary fibrous tumor, or other liposarcoma
|
|
| E.2.2 | Secondary objectives of the trial |
• To assess PFS based on either symptomatic progression or radiologic progression per RECIST v1.1
• To assess other clinical parameters
– Overall survival (OS)
– Overall response rate (ORR) based on RECIST v.1.1
– Radiologic PFS rate (PFR) at 12, 24, 48 and 52 weeks
– Predictive and response biomarkers
• To assess safety and tolerability of MORAb-004 in combination with G / D |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Be at least 18 years of age
2. Be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period
3. Have a histologically confirmed diagnosis of mSTS as defined by the 4 specified study subgroups
4. Have received 0 to 2 prior regimens of systemic treatment for mSTS. Systemic treatment regimens given in the neoadjuvant or adjuvant setting and maintenance therapies will not be considered as regimens in the metastatic setting for purposes of this protocol. Prior treatment with an anthracycline-based regimen is allowable but not required. (Subjects with extraskeletal small round blue cell sarcomas, must have exhausted or be intolerant of standard first line anthracycline-based chemotherapy. Subjects with rhabdomyosarcomas must have exhausted or be intolerant of standard first line therapy; anthracycline therapy for rhabdomyosarcoma is allowable but not required.) [French subjects only: Subjects will only be enrolled in the first line setting if (1) there is a contraindication to anthracycline treatment or (2) they have received anthracycline as adjuvant or neoadjuvant treatment.]
5. Have measurable disease, (per RECIST v.1.1) assessed within 30 days prior to the first dose of study drug. Subjects who are receiving second- or third-line therapy must have radiologically documented disease progression (per RECIST v1.1) present within 6 months prior to randomization. For subjects who are receiving first line therapy, no documentation of progression is required.
6. Have an interval between prior cancer treatment and first infusion of test article (MORAb-004 or placebo) of at least 2 weeks (If the immediately prior regimen of cancer treatment included an antibody, a therapeutic protein, or an investigational agent, the minimum interval between prior treatment and first infusion of study drug is 4 weeks.)
7. Have all toxicity (except alopecia) of most recent treatments controlled to a severity of less than or equal to a Grade 1 (mild) prior to administration of test article
8. Have laboratory test results within the 2 weeks prior to Study Day 1 as indicated below
– Absolute neutrophil count at least 1.5 × 109/L
– Platelet count at least 100 × 109/L
– Hemoglobin at least 8 g/dL
– Creatinine no greater than 1.5 × upper limit of normal (ULN) (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Grade 1)
– Bilirubin less than ULN, with the exception of subjects with Gilbert's disease. This inclusion criterion will be waived for subjects with Gilberts disease.
– Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), less than 2.5 × ULN (NCI CTCAE Grade 1) (Additionally, if ALT and/or AST >1.5 × ULN, alkaline phosphatase must be <2.5 × ULN. No adjustments to these criteria are made for subjects with hepatic metastases.)
– Activated partial thromboplastin time (aPTT) and prothrombin time (PT) less than 1.5 × ULN (NCI CTCAE Grade 1) (For subjects who are receiving anticoagulation, the aPTT and INR must be stable and considered baseline for the subject.)
9. Have a life expectancy of at least 3 months, as estimated by the investigator
10. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
11. Have tumor tissue available for biomarker studies (Tumor tissue from the original diagnostic biopsy is required. Tumor tissue from an optional biopsy of an accessible lesion at Screening may be submitted for biomarker studies. Additionally, tumor tissue obtained from a biopsy after the subject has received study drug and obtained at the investigator’s discretion may also be submitted for biomarker studies.)
12. Have any other significant medical conditions well-controlled and stable, in the opinion of the investigator, for at least 30 days prior to Study Day 1
13. Be willing and able to provide written informed consent
|
|
| E.4 | Principal exclusion criteria |
1. Have received more than 2 prior systemic treatment regimens for mSTS
2. Have received either gemcitabine or docetaxel in previous treatment for STS, regardless of the line of treatment
3. Have a diagnosis of primary bone sarcoma of any histologic type
4. Have evidence of active malignancy other than mSTS that required systemic or local treatment within the past 2 years (except basal cell or squamous cell skin cancer)
5. Have any other serious systemic disease (including active bacterial or fungal infection), any medical condition requiring current cytotoxic therapy, or current use of daily chronic (more than 4 consecutive weeks) systemic corticosteroid treatment
6. Have a history of clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class 3 or 4, angina not well-controlled by medication, or myocardial infarction within 6 months), a history of abnormal ejection fraction within the past 6 months (using institutional limits of normal), or a clinically significant arrhythmia on electrocardiograph (ECG) within the past 6 months
7. Have a medical condition with a high risk of bleeding, (e.g., a known bleeding disorder, a coagulopathy, or a tumor that involves the major vessels) or have a recent (within past 6 months) history of a significant bleeding event
8. Have undergone major surgical procedures or open biopsy, have significant traumatic injury within 30 days prior to the first date of study treatment, or have major surgical procedures anticipated during the study
9. Have active viral hepatitis or symptomatic HIV infection (Asymptomatic positive serology is not exclusionary.)
10. Have a current serious nonhealing wound, an ulcer (including gastrointestinal), or a bone fracture
11. Have a history of allergic reaction to prior monoclonal antibody or biologic agent
12. Have received previous treatment with MORAb-004 (anti-TEM-1)
13. Be currently breastfeeding, pregnant, or likely to become pregnant during the study
14. Have known central nervous system tumor involvement or metastases |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Efficacy:
PFS as measured by hazard ratio (HR) based on RECIST v1.1 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary Efficacy:
PFS based on either symtopmatic progression or radiologic progression per RECIST v1.1
Other clinical parameters
– OS
– ORR
– Radiologic PFR at 12, 24, 48 and 52 weeks
– Predictive and response biomarkers
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Secondary efficacy endpoints are PFS at 12 weeks; OS at 6, 12, 18 and 24 months; ORR; and radiologic PFR at 12, 24 ,48 and 52 weeks. |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 |
| Belgium |
| France |
| Italy |
| Netherlands |
| New Zealand |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| 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 |
Print
