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

NCT01337401 | Unknown Phase 2 DMC

• 5 other identifiers: ICR-CTSU/2010/100272010-021163-33CRUK/10/021ISRCTN63733470ISSRECE0036
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 11

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.

Conditions

Alveolar Soft-part Sarcoma

Keywords

Cediranib; ASPS; Sarcoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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)

Study Arms (2)

Blinded Cediranib

EXPERIMENTAL

Drug: Cediranib

Blinded Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Cediranib DRUG

30mg once daily, oral until disease progression

Blinded Cediranib

Placebo DRUG

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

Blinded Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Royal Marsden NHS Foundation Trust: collaborator

Study Sites (11)

Princess Alexandra Hospital

Brisbane, Australia

Location

Royal Prince Alfred Hospital

Sydney, Australia

Location

Hospital Santa Cruz i Sant Pau

Barcelona, Spain

Location

Hospital Puerta de Hierro

Madrid, Spain

Location

Hospital Miguel Servet

Zaragoza, Spain

Location

Bristol Haematology and Oncology Centre

Bristol, United Kingdom

Location

Royal Marsden Hospital

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

Christie Hospital

Manchester, United Kingdom

Location

Royal Victoria Infirmary/Freeman Hospital

Newcastle upon Tyne, United Kingdom

Location

Nottingham University Hospitals

Nottingham, United Kingdom

Location

Related Publications (1)

• Judson I, Morden JP, Kilburn L, Leahy M, Benson C, Bhadri V, Campbell-Hewson Q, Cubedo R, Dangoor A, Fox L, Hennig I, Jarman K, Joubert W, Kernaghan S, Lopez Pousa A, McNeil C, Seddon B, Snowdon C, Tattersall M, Toms C, Martinez Trufero J, Bliss JM. Cediranib in patients with alveolar soft-part sarcoma (CASPS): a double-blind, placebo-controlled, randomised, phase 2 trial. Lancet Oncol. 2019 Jul;20(7):1023-1034. doi: 10.1016/S1470-2045(19)30215-3. Epub 2019 May 31.

  PMID: 31160249 DERIVED

MeSH Terms

Conditions

Sarcoma, Alveolar Soft Part; Sarcoma

Interventions

cediranib

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2011
• First Posted: April 18, 2011
• Study Start: July 1, 2011
• Primary Completion: July 1, 2019
• Study Completion: January 1, 2020
• Last Updated: January 24, 2019

Record last verified: 2019-01

Locations

AU (2); ES (3); GB (6)