Table 2 Selected National Cancer Institute, U.S.

Phase I/II partially randomised study of Hedgehog antagonist GDC-0449 in combination with γ- Secretase Inhibitor RO4929097 in patients with advanced or metastatic sarcoma

Phase I/II

MSKCC-10049

10-049,8406,

NCT01154452

Sponsor: NCI

Lead Organisation:

Memorial Sloan-Kettering Cancer Centre

Age: 18 and over

Advanced sarcoma (Phase Ib)

Advanced, metastatic sarcoma (Phase II)

Expected enrolment (EE)120

(i) To determine maximum tolerated dose of RO4929097 when combined with GDC-0449 in patients with advanced sarcoma (Phase Ib).

(ii) To assess progression free survival (PFS) of patients with advanced, metastatic sarcoma treated with RO4929097 with or without GDC-0449.

Phase II study of AuroraA Kinase Inhibitor MLN8237 in paediatric patients with recurrent or refractory solid tumours or leukaemia

Phase II

COG-ADVL0921

ADVL0921

NCT01154816

Sponsor: NCI

Lead Organisation: Children's Oncology Group

Age: 1-21 years

Entry criteria includes patients with histological confirmed Ewing sarcoma/peripheral primitive neuroectodermal tumour

EE 190

Assess objective response rate in paediatric patients

Phase II study of Cixutumumab in patients with relapsed or refractory solid tumours

Cixutumumab: A fully human IgG1 monoclonal antibody directed against IGF-1R *

Phase II

COG-ADVL0821

ADVL0821

NCT00831844

Sponsor: NCI

Lead Organisation: Children's Oncology Group

Age: 6 months-30 years

Entry criteria includes patients with histological confirmed Ewing sarcoma/peripheral primitive neuroectodermal tumour

EE140

(i) Assess response rate

(ii) Toxicity

Secondary outcome:

Relationship between tumour expression of IGF-I, IGF-II, and IGF-IR and response*

Phase II study of MK8669 in patients with metastatic bone or soft-tissue sarcoma (8669-030)

MK8669 is a small molecule mTOR inhibitor and rapamycin analogue. mTOR is a serine/threonine kinase located downstream of the PI3K/Akt signalling pathway

Phase II

Sponsor: Pharmaceutical/Industry

Trial sites located in Japan

Age: 13 and over

Exclusion criteria include CNS metastasis (unless successfully treated), prior treatment with rapamycin or rapamycin analogues, on-going therapeutic toxicity from anticancer treatment, intercurrent or historic disease that may potentially confound results

Evaluation of MK 8669 when administered as maintenance therapy to patients with metastatic bone or soft-tissue sarcoma in Japan

IMC-A12 in combination with temsirolimus (CCI-779) in patients with advanced cancers

Phase I

2007-0595

MDA-2007-0595

8109

NCT00678223

NCT00678769

Sponsor: NCI

Lead organisation: M.D. Anderson Cancer Centre, University of Texas

Age: 16 and over

3-6 participants each dose level of IMC-A12 in combination with temsirolimus

(i) To establish the highest tolerable dose combination of IMC-A12 and temsirolimus that can be given to patients with advanced or metastatic cancer.

(ii) Establish drug safety.

Tolerability of dose scheduling

Biomarker studies incorporated

A phase I study of NK cell infusion following allogeneic peripheral blood stem cell transplantation from related or matched unrelated donors in paediatric patients with solid tumours and leukaemia's

Phase I

110073

11-C-0073

NCT01287104

NCI

Age: 4-35 years

Paediatric solid tumours (if ESFT must have ultra-high risk ESFT)

Re: EWS;

(i) If at initial diagnosis has bone or bone marrow metastasis may be enrolled if completed standard front line therapy (SFLT) that includes vincristine, cyclophosphamide, adriamycin, ifosfamide and etoposide (ii) Patients with recurrence of tumour at any site less than 1 year after completing SFLT or with subsequent recurrence any time after completing SFLT (iii) Patients with progressive or persistent disease while receiving standard front line chemotherapy

(i) To determine the safety, effectiveness, and immune system response of giving NK white blood cells to individuals who have received allogeneic HSCT.

(ii) To identify possible treatment related side effects.

Background: Based on laboratory evidence NK cells following allogeneic PBSCT may have a beneficial anti-cancer therapeutic effect

Studies of Temozolamide in combination with topotecan in refractory and relapsed paediatric solid tumours

Phase II

CSET 2008/1378

NCT 00918320

Lead organization: Institut Gustave Roussy

Age: 6 months - 20 years.

Eligibility criteria include: Confirmed paediatric solid tumour, relapsed/refractory tumours in which SFLT has failed, not more than 2 lines of prior chemotherapy, CT/MRI measurable disease

To determine that the combination of topotecan and temozolamide is effective in the treatment of relapsed and refractory solid neuroblastoma and other paediatric solid tumours.

PCI-24781 in combination with doxorubicin to treat sarcoma

A broad-spectrum phenyl hydroxamic acid inhibitor of histone deacetylase (HDAC). Inhibits several isoforms of HDAC causing accumulation of highly acetylated histones and induction of chromatin remodelling. It also inhibits homologous recombination (HR) activity by inhibiting the expression of RAD51

Phase I, II

Lead organisation/Sponsor

Massachusetts General Hospital

Age: 18 years and over

PCI-24781 is considered to regulate genes involved in tumour growth.

To determine safety and maximum tolerated dose of PCI-24781 that can be safety given with doxorubicin (phase I) and the the safety and efficacy of PCI-24781 when combined with doxorubicin (phase II) in patients with advanced sarcomas.

Study in localised and disseminated Ewing sarcoma

Phase III

Lead organisation/sponsor:

Medizinische Klinik und Poliklinik A-Universitaetsklinikum Muenster, Germany

Age: 4-50 years

EWING 2008 is a joint protocol of European and North American Ewing sarcoma study groups. Open to all patients diagnosed with Ewing sarcomas, localised or metastatic, who are considered eligible for neoadjuvant chemotherapy.

Standard Risk R1: Randomised trial

High Risk R2: Randomized trial

Very High Risk R3: Randomized trial

Refer to NCI website for full study details