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)Secondary Objectives:* To…
Source
Brief title
Condition
- Soft tissue neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
Primary Efficacy:
Progression Free Survival as measured by hazard ratio (HR), based on RECIST
v.1.1
Secondary outcome
Secondary Efficacy:
PFS based on either symptomatic progression or radiologic progression
per RECIST v1.1
- Other clinical parameters
* Overall Survival at 6, 12, 18 and 24 months
* Overall Response Rate
* Radiologic Progression Free Survival Rate at 12, 24, 48 and 52 weeks
- predictive and response biomarkers
Background summary
MORAb-004 is a humanized Immunoglobulin G-1-kappa (IgG1/*) antibody directed
against endosialin/tumor endothelial marker-1 (TEM-1; gene symbol CD248), a
cell surface glycoprotein, which is expressed in the stromal compartment of
nearly all human tumors, including fibroblasts and pericytes. In some human
tumors, TEM-1 expression is seen on tumor cells as well. This target has been
identified in 2 independent lines of research. Nonclinical studies have found
TEM-1 to play a key role in tumor growth and neovessel formation in numerous
cancer types including, but not limited to, renal, breast, colon, pancreatic,
lung, endometrial, ovarian, melanoma, sarcoma, and neuroectodermal
tumors. Specifically, Rouleau et al. found the TEM-1 was expressed by
malignant, perivascular and stromal cells in human clinical cancer specimens,
including specimens of advanced sarcoma, indicating that even advanced sarcomas
with poor prognosis might be good candidates for targeted therapy with an
antibody which binds to TEM-1.
Study objective
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)
Secondary Objectives:
* 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 Response Evaluation Criteria in Solid
Tumors (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
gemcitabine and docetaxel
Study design
This double-blind, placebo controlled study is being conducted to assess the
effectiveness of MORAb-004 to enhance the activity of the G/D combination and
to prolong PFS in subjects with mSTS.
This is a multicenter study of the efficacy and safety of the combination of
G/D plus MORAb-004 versus G/D plus placebo in subjects with mSTS.
Sites will enroll up to 200 subjects in the US, France, Italy, Belgium, the
Netherlands, New Zealand and Australia.
Intervention
All subjects in Part 2 will receive G/D as in Part 1 (i.e., gemcitabine 900
mg/m2 and docetaxel 75 mg/m2). Subjects randomized to Arm 1 will also receive
MORAb-004 infusions (MRP2D, maximum 8 mg/kg) on Days 1 and 8 of each cycle (see
Study Design section above). Subjects randomized to Arm 2 will receive G/D plus
placebo on Days 1 and 8 of each cycle. Subjects in Part 2 will be randomized to
one of the 2 arms at the time of entry into Part 2.
Part 1 of the protocol (optimum doses determination) will be done in hospitals
in the United States only.
Study burden and risks
Patients will have to come the hospital more frequently (weekly hospital
visits).
On Day 1 of each cycle they will receive two infusions, on Day 8 three
infusions.
More freqent CT- or MRI-scans
More frequent blood draws
Optional biopsy to collect tumor tissue for TEM-1 pathway determination.
Welsh Pool Road 210
Exton PA 19341
US
Welsh Pool Road 210
Exton PA 19341
US
Listed location countries
Age
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 been treated in the metastatic setting with 0 to 2 prior systemic regimens 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.
5. Have measurable disease, as defined by 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 of immediately prior treatments, except alopecia, controlled to a severity of less than or equal to Grade 1 (mild)
8. Have laboratory test results within the 2 weeks prior to Study Day 1 as indicated below
* Absolute neutrophil count at least 1.0 × 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 (NCI CTCAE Grade 1), with the exception of subjects with Gilbert's
disease. This inclusion criterion will be waived for subjects with Gilbert's disease
* Aspartate aminotransferase and alkaline phosphatase less than 2.5 × ULN (NCI CTCAE Grade 1) (Additionally if ALT or AST >1.5 x ULN, alkaline phosphatase must be < 2.5 x ULN)
* 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.) (see Section 5.7.2 for management of subjects receiving anticoagulation.)
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
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.
Exclusion criteria
1. Have received more than 2 prior systemic treatment regimens for mSTS
2. Have received either gemcitabine or docetaxel in any 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, or any medical condition requiring current cytotoxic therapy or current 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 the past 6 months), a history of abnormal ejection fraction within the past 6 months, using institutional limits of normal), or clinically significant arrhythmia on electrocardiograph (ECG) within the past 6 months
7. Have a medical condition with a high risk of bleeding 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 dsurgical procedures anticipated during the study.
9. Have active viral hepatitis or symptomatic HIV infection (Asymptomatic positive serology is acceptable)
10. Have a current serious non-healing would, and ulcer or 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2012-001399-12-NL |
ClinicalTrials.gov | NCT01574716 |
CCMO | NL41050.058.12 |