A phase I dose escalation study of cisplatin, pemetrexed and radiotherapy for inoperable stage III non-small cell lung cancer

Completed

• Conditions: ung cancer; Cancer; Lung cancer

• Registration Number: ISRCTN91946477
• Lead Sponsor: Erasmus Medical Center (The Netherlands)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-11-22
• Last Update Posted: 13 January 2015

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 39

Inclusion Criteria

1. Histologically or cytologically confirmed diagnosis (bronchial brushings and washings or Computed Tomography (CT)-guided fine needle aspiration) of NSCLC, stage III which is not amenable to surgical resection
2. Uni-dimensional or bi-dimensional disease on CT scans of the chest. Measurable tumour and/or nodal mass not exceeding 6 cm in largest diameter
3. Received no prior chemotherapy or radiation therapy
4. Performance Status zero to one on the World Health Organisation (WHO) scale
5. Estimated life expectancy of at least 24 weeks
6. Patient compliance and geographic proximity that allow adequate follow-up
7. Adequate bone marrow reserve:
a. White blood count (WBC) more than or equal to 3.0 x 10^9/L
b. platelets more than or equal to 100 x 10^9/L
c. haemoglobin more than or equal to 6 mmol/L (³ 9.6g/dl)
8. Adequate respiratory function: Forced expiratory volume in one second (FEV1) more than or equal to 1.0 L/s (more than 30%) and transfer factor for carbon monoxide (DLCO) more than or equal to 40% of predicted
9. Aged 18 years or over
10. Written informed consent from patients
11. Effective use of contraception for both males and females if appropriate during and for three months following end of study

Exclusion Criteria

1. Evidence of active infection at the discretion of the investigator
2. Inadequate liver function: bilirubin more than 1.5 times normal, Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) more than three times normal
3. Inadequate renal function: calculated creatinine clearance using Cockcroft-Gault formula of less than 60 ml/min
4. Hypercalcemia
5. Evidence of extrathoracic metastases/Stage IIIB with supraclavicular lymph nodes
6. Uncontrolled superior vena cava syndrome, haemoptysis causing a decrease of blood haemoglobin of more than or equal to 1 g/L (more than or equal to 0.062 mmol/L) in 24 hours, or other situations which make complete staging or treatment planning impossible
7. Pleural effusion with positive cytology
8. Pregnancy
9. Breast feeding
10. Serious concomitant systemic disorder incompatible with the study
11. Second primary malignancy (except in situ carcinoma of the cervix or adequately treated non-melanomatous skin cancer), unless off treatment and in remission for greater than five years
12. Use of any investigational agent in the month before enrolment into the study
13. Any co-morbid pulmonary disease that may put the patient at risk of toxicity, specifically interstitial lung disease (fibrosis) and serious chronic pulmonary disease
14. Patients who are unable to interrupt aspirin, other nonsteroidal anti-inflammatory drugs for a five day period starting two days before administration of pemetrexed (eight-day period for long acting agents such as piroxicam). Patients that cannot be treated with folic acid and vitamin B12 and dexamethasone
15. Presence of clinically detectable (by physical examination) third-space fluid collections, for example ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to the study entry
16. Use of growth factors

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary objective of this study is to determine the Maximum Tolerated Dose (MTD) of pemetrexed, cisplatin and radical involved-field radiotherapy in the treatment of patients with unresectable Stage III NSCLC. Two MTD?s will be determined:<br>1. MTD of pemetrexed and cisplatin in combination with conventional radiotherapy.<br>2. MTD of pemetrexed and cisplatin with hypofractionated radiotherapy.

Secondary Outcome Measures

Name	Time	Method
The secondary objectives of this study are the following:<br>1. The incidence and nature of acute toxicities.<br>2. The incidence and nature of delayed toxicity at three, six and 12 months after final radiotherapy treatment.<br>3. Objective tumour response.<br>4. Progression free survival.<br>5. Overall survival.