A Phase I/IIa trial of HA-Irinotecan, a formulation of hyaluronic acid and irinotecan, in the treatment of extensive stage small cell lung cancer and its effect on tumour stem cells.
- Conditions
- small cell lung cancerCancer - Lung - Small cell
- Registration Number
- ACTRN12611000520932
- Lead Sponsor
- Southern Health
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 40
Patients must fulfill all of the following criteria to be eligible for admission to the study:
18 years of age and older
Male or female
Histologically or cytologically confirmed small cell lung cancer, that is defined as a previously untreated metastatic or extensive disease:
Malignant pleural effusion or multifocal lung disease is considered metastatic or extensive disease.
Prior radiotherapy allowed.
Measurable disease, defined as 1 unidimensionally measurable lesion equal to1 cm by physical examination or radiographic techniques
Known brain metastases allowed.
Eastern Cooperative Oncology Group(ECOG) performance status 0-2
Life expectancy greater than 3 months
Haematology done within 7 days prior to first treatment and with initial values within the ranges specified below (transfusions are appropriate to bring patients into the appropriate ranges, however, there must be no evidence of active bleeding):
White Blood cell count greater than 3,000/mm^3
Absolute neutrophil count greater than 1,500/mm^3
Platelet count greater than 100,000/mm^3
Hemoglobin greater than 9.0 g/dL
Biochemistry done within 7 days prior to first treatment and with initial values within the ranges specified below:
Bilirubin greater than1.5 mg/dL
Alanine transaminase greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
Not pregnant or nursing
Negative pregnancy test
Women of child-bearing potential (WOCBP) and male partners of WOCBP must agree to use adequate contraception prior to study entry, throughout the study and for a period of 3 months after cessation of protocol therapy. WOCBP include any women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or are not postmenopausal (defined as amenorrhoea > 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level greater than 35 mIU/mL). Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or who are practicing abstinence or whose partner is sterile (eg., vasectomized) should be considered to be of child-bearing potential.
No medical disease that, in the opinion of the investigator, would preclude study treatment
Imaging investigations including at least chest computed tomography (CT) or Magnetic Resonane Imaging (MRI) scan and CT or MRI of abdomen/pelvis with other scans as necessary to document all sites of disease, done within 28 days prior to treatment. Contrast enhancement should be used if no contraindication. The same imaging method should be used for the patient throughout the entire study (e.g. if a patient starts with CT scans all subsequent imaging should be with CT scans).
At least 10 days since prior radiotherapy (including brain)
At least 2 weeks since prior and no concurrent anticonvulsants
No concurrent radiotherapy.
The patient must sign the consent form prior to registration.
The baseline assessment must be completed within 7 days prior to first treatment.
Patients must be accessible for treatment and follow-up. Investigators must assure themselves that patients registered on this trial will be available for complete documentation of the treatment, toxicity, and foll
Patients who fulfill any of the following criteria are not eligible for admission to the study:
Previous exposure to any chemotherapy for small cell lung cancer
Bilirubin greater than 1.5 mg/dL
ECOG greater than 2
Active inflammatory bowel disease or any chronic diarrhoea grade 2.
Bulky disease (>50% hepatic involvement, >25% lung involvement, or abdominal mass 10 cm) due to an increased risk of toxicity.
Radiotherapy within the preceding 4 weeks, unless to a single bone site.
Documented unsuitability for irinotecan includes known hypersensitivity to a camptothecin drug, abnormal glucuronidation of bilirubin or Gilbert’s syndrome.
Patients receiving treatment with phenobarbitone, St John’s Wort, phenytoin or valproate.
Partial or complete bowel obstruction.
Concomitant active infection.
Currently active second malignancy, other than non-melanoma skin cancers.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with interpretation of study results.
Pregnant or lactating women or women of childbearing potential not using adequate contraception.
Any active pathological condition that would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
Any condition (e.g., psychological, geographical) that does not permit compliance with the protocol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence of Grade 3 and 4 toxicity as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.02 (2009)[End of treatment (6 months folowing randomisation)];Tumour stem cell burden during and at conclusion of study as measured by CD44, CD133 stained cells from lung core biopsy[End of study (12 months following randomisation)]
- Secondary Outcome Measures
Name Time Method Cumulative dose of Irinotecan as measured by infusions received[End of treatment (6 months following randomisation)];Progression free survival rate at 6 months as measured radiologically[6 months post randomisation];Objective response rates as determined by computed tomography (CT) scans using RECIST 1.1[End of study (12 months following randomisation)];Quality of life as measured by 3 validated tools: McGill Quality of Life Quesionnaire (MQOL), Social Support Scale, and Hospital anxiety and depression scale (HADS)[End of study (12 months following randomisation)];Survival outcome by clinic visit/phone call[End of study (12 months following randomisation)]