Short treatment with the drug cyclophosphamide in bowel cancer

Phase 2

• Conditions: Stage II-IVA diagnosed colorectal cancer; Cancer; Bowel cancer

• Registration Number: ISRCTN12508004
• Lead Sponsor: Cardiff University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-16
• Last Update Posted: 6 May 2024
• Study Completion: 2028-09-03

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

1. Ability and willingness to provide written informed consent
2. Willing and able to comply with the trial visits and undergo treatment as scheduled
3. Age = 50 years
4. Clinical diagnosis of colorectal cancer stage II – IVA
5. Completed treatment by surgery ± adjuvant chemotherapy and deemed ‘cured’
6. For participants receiving adjuvant chemotherapy:
6.1. Last dose of chemotherapy must be completed = 4 weeks prior to first dose of trial therapy
6.2. First trial therapy dose must be started = 4 months from last chemotherapy dose
7. For participants not receiving adjuvant chemotherapy surgery must be = 6 weeks prior to first dose of trial therapy
8. WHO performance status 0 – 2
9. Female participants of childbearing potential (i.e. aged 50-55 in this study and not reached the menopause (postmenopausal state is defined as no menses for 12 months without an alternative medical cause)) have a negative urine pregnancy test and are not breastfeeding
10. Female participants of childbearing potential and male participants with a female partner of childbearing potential must agree to use appropriate methods of contraception (male condoms, ovulation-inhibiting hormonal contraception, intrauterine device (IUD), intrauterine hormone-releasing system (IUS) or abstinence) until 6 months following the date of their final dose of trial treatment

Exclusion Criteria

1. Creatinine level >1.5 Upper Limit of Normal (ULN)
2. Bilirubin level >1.5 ULN, Alkaline Phosphatase/Alanine Aminotransferase >2.5 ULN
3. Haemoglobin <90 g/L
4. Diagnosed as being immunosuppressed, receiving oral steroids (> prednisolone 10 mg daily) (nasal sprays and inhalers are permitted) or receiving other immunosuppressive therapy
5. Uncorrected urinary tract obstruction or active urinary tract infection
6. Participant has clinically active autoimmune disease requiring treatment to suppress autoinflammation
7. Known underlying inflammatory bowel disease that is considered to be the key aetiological agent in the development of the CRC
8. Currently active” second malignancy, other than non-melanoma skin cancer and previously diagnosed prostate cancer which is stable clinically = for more than 5 years with or without hormone treatment. (Participants are not considered to have a currently active” malignancy if they have completed therapy = more than 5 years previously and have no known evidence of residual or recurrent disease)
9. Evidence of significant clinical factor/s or laboratory finding which in the opinion of the investigating physician makes it undesirable for the patient to participate in the trial
10. No participant should have a serious or uncontrolled intercurrent infection or be HIV positive
11. A contra-indication to taking CPM:
11.1. Hypersensitivity to CPM, any of its metabolites, or to other components of the tablet
11.2. Acute infections
11.3. Bone-marrow aplasia
11.4. Acute urothelial toxicity from cytotoxic chemotherapy or radiation therapy
11.5. Pregnancy - participants of childbearing potential must agree to wait 6 months after stopping CPM before attempting to conceive a child.
12. Medications not permitted before, during and after the trial:
12.1. Anti-fungal drugs (4 weeks before/after or during trial treatment)
12.2. Anti-viral drugs (4 weeks before/after or during trial treatment)
12.3. Chemotherapy (4 weeks before/after trial treatment start)
12.4. Hormone therapy (4 weeks/after before and during trial treatment)
12.5. Adrenalin (4 weeks before/after and during trial treatment)
12.6. Immunosuppressive agents (4 weeks before/after and during trial treatment)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Disease free survival over 36 months from randomisation. Patients undergo standard clinical follow-up including at least two CT scans and six monthly serum CEA measurements (as recommended by NICE guideline on Colorectal cancer NG151). Disease recurrence or cancer-related death will be deemed an event. Recurrence will be evaluated at standard care appointments (timepoints depending on local site procedures) where potential disease relapse will be investigated by CT scan or other measures. Patient notes or discussion with patients' doctor will be used to determine disease free survival 3 years post-randomisation.

Secondary Outcome Measures

Name	Time	Method
1. Toxicity as measured by CTCAE over the course of treatment and up to 4 weeks after the last dose of cyclophosphamide. Toxicity will be monitored via blood tests during the week 4 visit (after the first cycle) for the first 50 participants receiving the IMP (cyclophosphamide). Treatment will be stopped should 15% of Grade 3/4 toxicity events be experienced at any stage and no further participants will be recruited, otherwise recruitment will continue. <br>Adverse event reporting will be performed at weeks 4, 7, 10 and 13 for all patients.<br>2. Immunological responses defined as =2-fold increase in anti-5T4 IFN-?+ T cell response at treatment day 22 v 1 and/or treatment day 64 v 43. Immune responses will be evaluated at baseline (week 1), during treatment (weeks 4 and 7) and post-treatment (weeks 10 and 13) in ~100 patients (local to Cardiff). Translational analysis will be performed after 25 and 50 participants are recruited to each group i.e. active monitoring group vs cyclophosphamide group.