A Phase II, Double-blind, Placebo-Controlled, Randomised Study to Assess the Efficacy and Safety of ZD4054 in Combination with Pemetrexed (Alimta®) vs. Pemetrexed Alone in Patients with Non-small Cell Lung Cancer who Have Failed One Prior Platinum-based Chemotherapy Regimen.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 64

Inclusion Criteria

1. Provision of written informed consent.
2. Female or male aged 18 years or older.
3. Histologically or cytologically confirmed locally advanced or metastatic NSCLC on entry into study, where the histology is not predominantly of squamous type.
4. Patients requiring treatment that meet one of the following criteria:
- Have progressed following one prior platinum-based chemotherapy regimen for locally advanced or metastatic disease;
- Have progressed within 6 months of adjuvant platinum-based chemotherapy.
5. World Health Organisation (WHO) performance status 0-2.
6. Life expectancy of > 12 weeks.
7. Patient suitable for treatment with pemetrexed.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior treatment with pemetrexed in the last 12 months.
2. Prior therapy with an ET receptor antagonist.
3. Any recent surgery, unhealed surgical incision, severe concomitant medical condition (eg, unstable cardiac, hepatic or renal disease) or significant laboratory finding which, in the Investigator’s opinion, makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the study protocol.
4. New York Heart Association Stage II, III or IV cardiac failure or myocardial infarction in the 6 months prior to randomisation.
5. Current or prior malignancy within previous 3 years (other than NSCLC or adequately treated basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix).
6. Brain metastases or spinal cord compression unless treated and stable off steroids for 1 month.
7. History of past or current epilepsy, epilepsy syndrome or other seizure disorder.
8. Uncontrolled superior vena cava syndrome.
9. Any unresolved toxicity = Common toxicology criteria (CTC) grade 2 from previous anticancer therapy (unless specified elsewhere within these criteria).
10. Less than 4 weeks since completion of prior radiotherapy to the primary tumour or persistence of any acute radiotherapy toxicity.
11. Corrected QT interval (QTc) > 470 msec using Bazett’s formula.
12. Patients with factors that increase risk of QTc prolongation or arrhythmic events such as heart failure, hypokalaemia, family history of long QT syndrome or any concomitant medication known to prolong QTc.
13. Any of the following laboratory values:
- Total bilirubin > 1.5 x upper limit of normal (ULN) unless patient has confirmed Gilbert’s syndrome.
- Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULN or alkaline phosphatase (ALP) > 3 x ULN if no demonstrable liver metastases or ALT or AST or ALP > 5 x ULN in the presence of liver metastases.
- Platelets < 100 x 10 to the power of 9 /L;
- Haemoglobin < 9 g/dL despite transfusion;
- Absolute neutrophil count (ANC) < 1.5 x 10 to the power of 9 /L;
- Creatinine clearance = 50 mL/min determined using either the Cockcroft and Gault equation or with a 24-hour urine collection.
- Presence of clinically significant blood or protein in urine sample.
14. Use of drugs that are potent inducers of CYP450 (eg, phenytoin, rifampicin, carbamazepine, phenobarbitone, St John’s Wort) within 2 weeks of randomisation. Dexamethasone, a known inducer of CYP2D6 and CYP3A4, may be used as premedication for pemetrexed.
15. Use of systemic retinoids within 2 weeks of randomisation.
16. History of hypersensitivity to active or inactive excipients of any study medication (ZD4054/placebo, polysorbate 80, pemetrexed) or family history of hypersensitivity to ET receptor antagonists.
17. Pregnancy, breastfeeding or women of child-bearing potential not using an effective method of birth control
18. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff, staff at the study site or representatives of AstraZeneca).
19. Previous enrolment or randomisation of treatment in the present study.
20. Known risk of transmitting human immunodeficiency virus or Hepatitis B or C via infected blood.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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