A Trial of Cediranib in the Treatment of Patients With Alveolar Soft Part Sarcoma (CASPS)

Sponsor

Institute of Cancer Research, United Kingdom (Other)

Overall Status

Unknown status

CT.gov ID

NCT01337401

Collaborator

Royal Marsden NHS Foundation Trust (Other)

Enrollment

Locations

Arms

102

Anticipated Duration (Months)

3.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is a two-arm, randomised, double-blind, international, multi-centre phase II trial of cediranib in Alveolar Soft Part Sarcoma (ASPS).

The study aims to confirm the ability of cediranib to halt disease progression in patients with metastatic ASPS, as measured by the change in tumour size at 24 weeks after randomisation, and to produce objective response according to RECIST criteria.

Condition or Disease	Intervention/Treatment	Phase
Alveolar Soft-part Sarcoma	Drug: Cediranib Drug: Placebo	Phase 2

Detailed Description

Patients aged 16 years and older with a histologically confirmed diagnosis of ASPS will be recruited. Eligible patients will be randomised to receive cediranib (30 mg daily po) or placebo (30 mg daily po) in a 2:1 ratio. At 24 weeks post randomisation, treatment will be unblinded after which time all patients on placebo and those who have not progressed on active treatment will be given cediranib. Treatment will then continue until objective disease progression or death.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of Cediranib in the Treatment of Patients With Alveolar Soft Part Sarcoma (CASPS)

Actual Study Start Date :

Jul 1, 2011

Anticipated Primary Completion Date :

Jul 1, 2019

Anticipated Study Completion Date :

Jan 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Blinded Cediranib	Drug: Cediranib 30mg once daily, oral until disease progression
Placebo Comparator: Blinded Placebo	Drug: Placebo 30mg, once daily, oral until 24 weeks or disease progression if sooner

Arm

Intervention/Treatment

Experimental: Blinded Cediranib

Drug: Cediranib

30mg once daily, oral until disease progression

Placebo Comparator: Blinded Placebo

Drug: Placebo

30mg, once daily, oral until 24 weeks or disease progression if sooner

Outcome Measures

Primary Outcome Measures

To evaluate the efficacy of cediranib in the treatment of ASPS by measuring the percentage change in the sum of target marker lesion diameters from randomisation to week 24 (or progression if sooner) compared to treatment with placebo. [24 Weeks of treatment]

Secondary Outcome Measures

Response rate at week 24, best response using RECISTv1.1 and best reduction (%) in tumour size [24 Weeks of treatment]
Progression-free survival and percentage alive and progression-free at 12 months (APF12) [12 months of treatment]
Length of Overall survival [Patients will be followed up every 12 weeks]
The safety and tolerability profile of cediranib in patients with ASPS [Assessments will be made at every study visit (8-12 weekly)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of ASPS (central confirmation not required at study entry)
Age 16 years and older
Availability of archived tissue blocks or unstained slides to enable confirmation of t(X;17) translocation
ECOG Performance Status of 0-1
Life expectancy of >12 weeks
Progressive disease as defined by RECIST v1.1 within 6 months prior to randomisation
Measurable metastatic disease using RECISTv1.1, i.e. at least one lesion 10 mm in diameter (15 mm in short axis for nodal lesions) assessable by CT (or MRI for brain metastases).
Patients with brain metastases are permitted provided disease is controlled with a stable dose of corticosteroid and/or non-enzyme inducing anticonvulsant
The capacity to understand the patient information sheet and ability to provide written informed consent
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
Able to swallow and retain oral medication

Exclusion Criteria:

Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count ≤1.5 x 109/L or platelet count ≤100 x 109/L
Serum bilirubin ≥ 1.5 x ULN (unless Gilbert's syndrome)
ALT or AST ≥ 2.5 x ULN. If liver metastases are present, ALT or AST > 5 x ULN
Serum creatinine > 1.5 x ULN or a creatinine clearance (calculated or measured) of ≤ 50mL/min
Greater than +1 proteinuria unless urinary protein < 1.5g in a 24 hr period or protein/creatinine ratio < 1.5.
History of significant gastrointestinal impairment, as judged by the Investigator, that would significantly affect the absorption of cediranib.
Patients with a history of poorly controlled hypertension with resting blood pressure

150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy.

Any evidence of severe or uncontrolled co-morbidities e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease, or active and uncontrolled infection.
Evidence of prolonged QTc >480 msec (using Bazetts correction, for which the formula is: QTc = QT/√RR) or history of familial long QT syndrome.
Significant recent haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in previous 4 weeks).
Major thoracic or abdominal surgery in the 14 days prior to entry into the study, or a surgical incision that is not fully healed.
Pregnant or breast-feeding women; women of childbearing potential with a positive pregnancy test prior to receiving study medication; women the intention of pregnancy during study treatment; women of child bearing potential unwilling to have a urine or serum pregnancy test prior to study entry (even if surgically sterilised).
Men and women of childbearing potential unwilling to use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilisation) for the duration of the study and should continue such precautions for 2 weeks after receiving the last study treatment.
History of anticancer (including investigational, non-registered) treatment in the four weeks prior to first dose of cediranib, with the exception of palliative radiotherapy for symptom control.
Previous treatment with cediranib.
Known hypersensitivity to any excipient of cediranib.
History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the patient has been disease free for 2 years and there is a tissue diagnosis of the primary cancer of interest from a target lesion.
Other concomitant anti-cancer therapy (including LHRH agonists) except steroids
Recent history of thrombosis
Patients with brain metastases if they are symptomatic requiring increasing steroids in the previous six weeks to study entry or those with evidence of recent and/or active bleeding, or those causing uncontrolled seizures.

Contacts and Locations

Locations

	Site	City	Country
1	Princess Alexandra Hospital	Brisbane	Australia
2	Royal Prince Alfred Hospital	Sydney	Australia
3	Hospital Santa Cruz i Sant Pau	Barcelona	Spain
4	Hospital Puerta de Hierro	Madrid	Spain
5	Hospital Miguel Servet	Zaragoza	Spain
6	Bristol Haematology and Oncology Centre	Bristol	United Kingdom
7	Royal Marsden Hospital	London	United Kingdom
8	University College London Hospital	London	United Kingdom
9	Christie Hospital	Manchester	United Kingdom
10	Royal Victoria Infirmary/Freeman Hospital	Newcastle-Upon-Tyne	United Kingdom
11	Nottingham University Hospitals	Nottingham	United Kingdom