A Phase III, Multicentre, Randomised, Double-Blind Study to Assess the Safety and Efficacy of Emactuzumab vs. Placebo in Subjects with Tenosynovial Giant Cell Tumour.
- Conditions
- Tenosynovial Giant Cell Tumour, CancerMalignant giant cell tumortenosynovial giant cell tumor (TGCT)10013361
- Registration Number
- NL-OMON51288
- Lead Sponsor
- SynOx therapeutics Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 3
1. Written informed consent.
2. 2. Biopsy-confirmed (standard of care diagnosis history) local or diffuse
TGCT where surgical resection would be associated with predicted worsening
functional limitations due to surgical damage to the joint and adjacent soft
tissues, and/or subject presents with an anticipated high risk of early
recurrence as determined by a multidisciplinary tumour board or equivalent*, or
any other morbidity associated with the surgery, and/or surgical treatment is
not expected to improve the clinical outcomes of the subject.
*The multidisciplinary tumour board or equivalent must comprise at least 2
individuals: the Investigator plus at least one other qualified physician
(orthopaedic surgeon or medical oncologist) not involved in this study
3. Measurable disease: longest diameter >=20 mm.
4. Age >12 years.
5. Adequate organ and bone marrow function: haemoglobin (Hb) >10.0 g/dL,
neutrophils >1.5 × 109/L and platelets >100 × 109/L.
6. Minimum mean score of 4 on NRS for Worst Pain during 7 days prior to
randomization,
based upon a minimum of 4 days of completed diary data.
7. Minimum mean score of 4 on NRS for Worst Stiffness during 7 days prior to
randomization, based upon a minimum of 4 days of completed diary data.
8. Women of childbearing potential (WOCBP) must have a negative urine and serum
pregnancy test prior to starting treatment. WOCBP must agree to use a highly
effective method of contraception throughout the treatment period and for 7
months after discontinuation of treatment. Acceptable methods of contraception
according to protocol description.
9. For Open-Label Phase ONLY:
Subjects must either:
-Have responded based on RECIST v1.1 (CR or PR) to initial treatment with
emactuzumab during the Double-Blind Phase and then progressed (objective
progressive disease on imaging) within 9-18 months of initial treatment on D 1
(Visit 1) with a minimum 6-month washout period between treatments; or
-Have received placebo and completed the 6-month visit on D 181/Visit 10
(3 months treatment and 3 months observation) of the Double-Blind Phase and
have not completed more than 18 months of the study since initial treatment on
D1 (Visit1).
1. Pregnant or breast feeding.
2. Medical conditions, including auto-immune, requiring systemic
immunosuppression. Any
systemic treatment for these conditions (eg, glucocorticoids) is not allowed
within
4 weeks of Screening and during the study. All Lupus Erythematosus are excluded
irrespective of treatment.
3. Metastatic TGCT.
4. TGCT currently affecting multiple joints.
5. Pexidartinib therapy within 3 months of Screening.
6. otinib, imatinib; other chemotherapy, radiotherapy, or investigational
therapy within 4
weeks of Screening.
7. Unresolved clinically significant toxicity from a previous treatment or any
history of
serious liver toxicity.
8. Current or chronic history of liver disease. This includes, but is not
limited to, hepatitis
virus infections, drug- or alcohol-related liver disease, nonalcoholic
steatohepatitis,
autoimmune hepatitis, haemochromatosis, Wilson*s disease, a-1 antitrypsin
deficiency,
primary biliary cholangitis, primary sclerosing cholangitis, or any other liver
disease
which in the opinion of the Investigator is considered clinically significant.
9. Renal function: creatinine clearance <60 mL/min (Cockcroft-Gault formula).
10. Liver function: ALT >3.0 × ULN; OR total bilirubin >1.5 × ULN.
11. Within 6 months of baseline has experienced: clinically significant
myocardial infarction,
severe/unstable angina pectoris, congestive heart failure New York Heart
Association
(NYHA) Class III or IV, or pulmonary disease (NYHA Criteria 1994).
12. Clinically significant active infection requiring systemic antibiotic
treatment.
Rescreening may occur any time after 7 days post completion of treatment.
13. Systemic antiretroviral therapy within 3 months of baseline.
14. Other active cancer that requires concurrent treatment or history of
malignancy other than
TGCT, unless there is the expectation that the malignancy has been cured, and
tumor
specific treatment for the malignancy has not been administered within the
previous
5 years.
15. Planned surgery during the course of the study with the exception of dental
treatment.
16. Inability to comply with the study procedures.
17. For the Double-Blind Phase ONLY:
Previous exposure to emactuzumab and/or neutralizing antibodies.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Objective response rate by 6 months from initiation of therapy based on<br /><br>independent, blinded central review</p><br>
- Secondary Outcome Measures
Name Time Method