PLATO - PersonaLising Anal cancer radioTherapy dOse - Incorporating Anal Cancer Trials (ACT) ACT3, ACT4 and ACT5
Anal cancer
Current interventions as of 03/04/2023: ACT3 (recruitment end date: 31/10/2023): Observation arm No further treatment after local excision. Intervention arm Either a 3D conformal plan or a single phase inverse-planned IMRT treatment plan delivered with multiple fields, or arc techniques. Choice of delivery technique is at the discretion of the treating clinician. PTV_A = 41.4Gy in 23F (1.8Gy per F) in 4.5 weeks Chemotherapy: Mitomycin C 12mg/m2 iv Day 1 & Capecitabine 852mg/m2 oral bd 5 days/week (on days of radiotherapy) for 23 days ACT4 (recruitment end date: 01/12/2020): All patients will receive IMRT where different dose fractionations are delivered to the elective nodal region (PTV_E) and to the areas of gross tumour (PTV_A). A single phase inverse-planned IMRT treatment plan should be produced and delivered with multiple fields or arc techniques. Standard-dose arm PTV_A: 50.4Gy in 28F in 5.5 weeks PTV_E: 40.0Gy in 28F in 5.5 weeks Chemotherapy: Mitomycin C 12mg/m2 iv Day 1 & Capecitabine 852mg/m2 oral bd 5 days/week (on days of radiotherapy) for 28 days Reduced-dose (experimental) arm PTV_A: 41.4Gy in 23F in 4.5 weeks PTV_E: 34.5Gy in 23F in 4.5 weeks Chemotherapy: Mitomycin C 12mg/m2 iv Day 1 & Capecitabine 852mg/m2 oral bd 5 days/week (on days of radiotherapy) for 23 days ACT5 (recruitment end date: 31/08/2023): All patients will receive IMRT where different dose fractionations are delivered to the elective nodal region (PTV_E) and to the areas of gross tumour (PTV_A and PTV_N). A single phase inverse-planned IMRT treatment plan should be produced and delivered with multiple fields or arc techniques. Standard-dose arm PTV_A: 53.2.Gy in 28F in 5.5 weeks PTV_N: 50.4Gy in 28F in 5.5 weeks (involved nodes ≤3cm) 53.2Gy in 28F in 5.5 weeks (involved nodes >3cm) PTV_E: 40.0Gy in 28F in 5.5 weeks Dose escalation arm 1 PTV_A: 53.2Gy in 28F in 5.5 weeks PTV_Boost: 58.8Gy in 28F in 5.5 weeks PTV_N: 53.2Gy in 28F in 5.5 weeks (involved nodes ≤3cm) 53.
Key inclusion criteria for all three trials include: 1. Provision of written informed consent 2. Histologically-proven, invasive primary squamous, basaloid, or cloacogenic carcinoma of the anus 3. Adequate bone marrow, hepatic and renal function 4. HIV negative or HIV positive and receiving effective antiretroviral therapy and CD4 count >200 5. Aged 16 years or over 6. Fit for all protocol defined treatments 7. Prepared to practice methods of contraception during treatment and until 6 months post end of treatment 8. Able to undergo all mandated staging and follow-up investigations, including MRI Trial-specific inclusion criteria: ACT3 T1 N0 or Nx anal margin tumour treated by local excision; ECOG performance status 0-2 ACT4 T1-2 up to 4cm N0 or Nx anal canal or anal margin tumour; ECOG performance status 0-1 ACT5 T2 N1-3 or T3-4 Nany anal canal or anal margin tumour; ECOG performance status 0-1
Key exclusion criteria for all three trials include: 1. Definite evidence of metastatic disease 2. Prior invasive malignancy unless disease-free for a minimum of 3 years (exluding basal cell carcinoma of the skin or other in situ carcinomas) 3. Prior systemic chemotherapy for anal cancer 4. Prior radiotherapy to the pelvis 5. Uncontrolled cardiorespiratory comorbidity 6. Pregnant or lactating 7. Immunocompromised (organ transplant) Trial-specific exclusion criteria: ACT3 Where a piecemeal local excision precludes assessment of tumour size and margin status