Trial assessing modified denosumab treatment as option for patients with a giant cell tumor of the bone, which cannot be treated by surgery or where surgery is not the best optio

Phase 1

• Conditions: Giant cell tumor of bone; MedDRA version: 20.0Level: LLTClassification code 10005968Term: Bone giant cell tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002096-17-GB
• Lead Sponsor: European Organisation for Research and Treatment of Cancer (EORTC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-02-11
• Last Update Posted: 18 March 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

* Histologically proven primary or metastatic unresectable GCTB or resectable GCTB but not a candidate for surgery, excluding primary or metastatic GCTB in the jaw.
* Evidence of active disease at time of registration based on local investigator's assessment
Note: Active disease is defined as any lesion increased in size and/or any osteolytic lesion with increased bone disruption and/or increase of tumor-associated symptoms
* Age = 18 years old
* Patient must have received denosumab before entering this trial:
- The duration of treatment with full dose denosumab (120 mg SC ) as per current label must be at least 12 months and patient may have received up to 15 months of denosumab. Note: for patients who temporarily discontinued tratement and then restarted reaching a total treatment duration of 15 months, the Sponsor should be contacted and eligibility evaluated on a per patient basis.
- And patient must have received at least 12 doses of denosumab 120 mg before entering into this trial.
* ECOG/WHO PS 0-2
* Albumin-adjusted serum calcium level = 2.0 mmol/L (8.0 mg/dL)
* Representative formalin fixed, paraffin embedded tumor blocks or unstained tissue slides,either from the primary tumor or a metastatic lesion, must be available for histological central review.
* Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first reduced dose of study treatment.
Note: a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
* WOCBP should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 5 months after the last treatment cycle. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
- Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner
Note: Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success.
- Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
* Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 5 months after the last study treatment.
* Before patient registration, wr

Exclusion Criteria

* Currently receiving other GCTB specific treatment (eg, radiation, chemotherapy, or embolization)
* Concurrent bisphosphonate treatment and calcitonin
* Known or suspected current diagnosis of underlying malignancy including high-grade sarcoma, osteosarcoma, fibrosarcoma, malignant giant cell sarcoma
* Known diagnosis of second malignancy within the past 5 years (subjects with definitively treated basal cell carcinoma and cervical carcinoma in situ are permitted)
* Creatinine clearance < 30 mL/min
* Hemoglobin < 10.0 g/dL or 6.2 mmol/L
* Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
* Active dental or jaw condition which requires oral surgery, including tooth extraction
* Non-healed dental/oral surgery
* Planned invasive dental procedure for the course of the study
* Known hypersensitivity to the active substance or to any of the excipients (glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 20)
* Treatment with other investigational device or drug 30 days prior to registration
* Known hypersensitivity to products to be administered during the study (calcium and/or vitamin D)
* Unstable systemic disease including active and uncontrolled infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before registration
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified