None listed
Conditions
Brief summary
This study looks at the effectiveness of the chemotherapy drug cyclophosphamide in combination with pemetrexed-based chemotherapy in people with advanced malignant mesothelioma or advanced non-small cell lung cancer receiving first or second line palliative treatment. Participants will all receive low-dose repeat treatment with cyclophosphamide in combination with the conventional dose of pemetrexed-based chemotherapy commencing from the second cycle of chemotherapy, up to a maximum of 6 cycles. Patients will be monitored for safety at the beginning of treatment, weekly whilst on treatment, and at 90-days follow-up. The tumour will be assessed on CT scan at baseline, after every 2 cycles of treatment, and at least 3 monthly after the completion of treatment, until any progression of the disease. The study aims to see whether this treatment is effective by improving the way the immune system reacts against the cancer by assessing the number/activation/proliferation of various immune cells from weekly blood tests taken at baseline, weekly whilst on chemotherapy, and at 90-day follow-up visit.
Interventions
Cyclophosphamide taken orally once daily (dose ranges from 50mg to 150mg and is titrated according to toxicities and nadir blood T-reg % from last cycle chemotherapy) for the first 14 days of each of cycles 2-6. Each cycle is scheduled to last 21 days.
Pemetrexed-based chemotherapy regimens include as follows:
Pemetrexed single agent 500mg/m2 given IV day 1 of each 21 day cycle.
OR
Cisplatin 75 mg/m2 given IV and pemetrexed 500 mg/m2 given IV day 1 of each 21 day cycle.
OR
Carboplatin AUC 4-6 g
Cyclophosphamide taken orally once daily (dose ranges from 50mg to 150mg and is titrated according to toxicities and nadir blood T-reg % from last cycle chemotherapy) for the first 14 days of each of cycles 2-6. Each cycle is scheduled to last 21 days. Pemetrexed-based chemotherapy regimens include as follows: Pemetrexed single agent 500mg/m2 given IV day 1 of each 21 day cycle. OR Cisplatin 75 mg/m2 given IV and pemetrexed 500 mg/m2 given IV day 1 of each 21 day cycle. OR Carboplatin AUC 4-6 given IV and pemetrexed 500 mg/m2 given IV day 1 of each 21 day cycle. Patients will receive treatment for a maximum of 6 cycles. All pemetrexed-containing regimens will be accompanied by vitamin B12 injection 1000IU 9 weekly and folic acid 0.5 mg daily for the duration of chemotherapy and for at least one month following cessation of chemotherapy as per standard practice.
Sponsors
Sir Charles Gairdner Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) or malignant mesothelioma (MM) planned for treatment with a pemetrexed-containing regimen. Treatment of advanced disease with palliative intent. First or second line treatment. Measureable or evaluable disease as defined by the RECIST criteria (NSCLC) or Modified RECIST (MM). Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Exclusion criteria
History of severe autoimmune disease. Radiotherapy to all areas of measureable disease. Previous or concurrent malignancy diagnosis (except curatively-treated basal cell carcinoma (BCC) of skin, carcinoma in situ of cervix) unless treated with curative intent more than 5 years before enrolment. Concomitant requirement for oral corticosteroids for more than 5 days of each treatment cycle. Concomitant treatment with other investigational agents or immunotherapy. Pregnant or breast feeding.
Outcome results
None listed