Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma

NCT01310855 | Terminated Phase 2 Results DMC

• 5 other identifiers: CDR0000696313UCL-10/0035ZENECA-ISSRECE00002EUDRACT-2010-021531-13CRUKE/10/044
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 10

Brief Summary

RATIONALE: Cediranib Maleate and gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether cediranib maleate given together with gefitinib is more effective than cediranib maleate given alone in treating patients with recurrent or progressive glioblastoma. PURPOSE: This randomized phase II trial is studying the side effects of giving cediranib maleate together with gefitinib and to see how well it works compared with giving cediranib maleate together with a placebo in treating patients with recurrent or progressive glioblastoma.

Conditions

Glioblastoma

Keywords

adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma; recurrent adult brain tumor

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression free survival (PFS) defined as the time from the date of randomisation to the date of first progression or death due to any cause, whichever one comes first. The progression definition will be based on modified RANO criteria (Wen 2010), such that progression will be defined as the earliest time that at least one of the following occurs: 1. Clinical deterioration 2. Failure to return for evaluation as a result of death or deteriorating condition Or, by retrospective radiographic central review: 3. Any new lesion 4. Increase in ≥25% of sum of the products of perpendicular diameters of enhancing lesions compared with baseline scan, on stable or increasing doses of steroids (dexamethasone) compared to baseline (T1 post-contrast scan) 5. Clear progression of non-measureable disease 6. Significant increase in T2/FLAIR non-enhancing lesion - on stable or increasing steroids (dexamethasone) compared with baseline or best response not caused by co-morbid events.

  from the date of randomisation to the date of first progression or death due to any cause, until 6 months from the date the last patient finished trial treatment (the day after the date that the last trial drug was taken)

Secondary Outcomes (6)

• Overall Survival

  from date of randomization to date of Death due to any cause.

• Radiographic Response Rate

  from baseline scan to six week and 12 week scans

• Progression-free Survival Rate at 6 Months

  from the date of randomisation to 6 months

• Steroid Use

  from randomization to first increase in dexamethasone dose

• Time to Deterioration of Neurological Status

  from date of randomization to the date of first neurological status worsening in comparison to baseline (first of 2 confirmatory reports at 2 consecutive visits, 6 weeks apart) as assessed by the clinician, or until date of death, whichever is first.

Study Arms (2)

Cediranib & Gefitinib

ACTIVE COMPARATOR

Cediranib maleate 30mg od orally and gefitinib 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit.

Drug: cediranib maleate; Drug: gefitinib

Cediranbib & placebo

PLACEBO COMPARATOR

Cediranib maleate 30mg od orally and placebo 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit.

Drug: cediranib maleate; Drug: Placebo

Interventions

cediranib maleate DRUG

Cediranbib & placebo; Cediranib & Gefitinib

gefitinib DRUG

Cediranib & Gefitinib

Placebo DRUG

Cediranbib & placebo

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed glioblastoma * Measurable disease by MRI * Completed standard first-line treatment for glioblastoma including surgery (unless not received due to anatomical location), radiotherapy and temozolomide (last dose given at least 28 days prior to enrollment) * No other prior treatment for glioblastoma except Gliadel or steroids * Recurrent or progressive disease after standard first-line treatment * No disease progression within 3 months of completion of radiotherapy * No intra- or peri-tumoral hemorrhage PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Mini-mental status score ≥ 15 * Life expectancy ≥ 12 weeks * Serum bilirubin, ALT/AST, creatinine, and urine protein normal * Adequate bone marrow reserve * Not pregnant or nursing * Normal ECG * No history of familial long QT syndrome * No absorption or swallowing difficulties * No uncontrolled hypertension or cardiac ventricular arrhythmias * No current or history of uncontrolled hypertension or requiring maximal doses of calcium channel blockers * No severe or uncontrolled disease * No history of lung disease * No recent hemorrhage or hemoptysis * No known hypersensitivity to cediranib maleate, gefitinib, or any excipients * No history of other malignancies except adequately treated basal cell or squamous cell carcinoma or carcinoma in situ within the past 5 years, unless disease-free for 2 years with tissue diagnosis * No known HIV positivity * No known hepatitis B or C infection * No unhealed surgical incision * Not involved in planning or conducting this study PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior anticancer therapy, including radiotherapy * At least 3 months since prior cranial radiation * At least 30 days since prior investigational drugs * At least 28 days since prior craniotomy * At least 2 weeks since prior enzyme-inducing antiepileptic drugs * At least 2 weeks since prior and no concurrent dexamethasone (\> 8 mg/day) or equivalent * At least 14 days since prior major surgery or brain biopsy * No concurrent steroids OR on stable dose 5 days prior to baseline MRI * No other concurrent anticancer therapy, except for steroids (dexamethasone only) * No previous enrollment on the current study * No prior inhibitors of angiogenesis, EGFR, or downstream targets * No prior radiosurgery or brachytherapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University College, London: lead
• AstraZeneca: collaborator

Study Sites (10)

University College Hospital

London, England, NW1 2BU, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Royal Surrey County Hospital

Guildford, United Kingdom

Location

Castle Hill Hospital

Hull, United Kingdom

Location

Charing Cross Hospital

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Royal Marsden Hospital

Sutton, United Kingdom

Location

Related Publications (1)

• Brown N, McBain C, Nash S, Hopkins K, Sanghera P, Saran F, Phillips M, Dungey F, Clifton-Hadley L, Wanek K, Krell D, Jeffries S, Khan I, Smith P, Mulholland P. Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma. PLoS One. 2016 May 27;11(5):e0156369. doi: 10.1371/journal.pone.0156369. eCollection 2016.

  PMID: 27232884 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

cediranib; Gefitinib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Mark Phillips
• Organization: UCL and CTC Cancer Trials Centre

ctc.doric@ucl.ac.uk

0207 679 9139

Study Officials

• Paul Mulholland, PhD, MRCP, MSC, MBBS

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: March 5, 2011
• First Posted: March 9, 2011
• Study Start: May 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: January 1, 2014
• Last Updated: May 31, 2017
• Results First Posted: January 27, 2017

Record last verified: 2017-05

Locations

GB (10)