Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00025090
Protocol/serial number
ACT II
Study information
Scientific title
A second UK Phase III anal cancer trial: a trial of chemoradiation and maintenance therapy for patients with anal cancer
Acronym
ACT II
Study hypothesis
Following completion of ACT I the standard treatment for anal cancer is a combined modality treatment of radiotherapy, 5-Fluorouracil (5-FU) and mitomycin. However, the schedule used in ACT I may not be optimal and an improvement in outcome may be achieved by intensifying.
United Kingdom, European Organisation for Research and Treatment of Cancer (EORTC) and Intergroup pilot studies used three main approaches:
1. Modification of radiotherapy schedule
2. Changing the chemotherapy regimen
3. Additional courses of chemotherapy.
As a result, to avoid using split course radiotherapy a continuous course of radiotherapy (piloted in over 80 patients) will be used in this trial, cisplatin will be compared to mitomycin and patients will be randomised to maintenance chemotherapy.
Cisplatin was chosen as in combination with 5-FU it is active in advanced disease, it produces high Complete Remission (CR) rates in combination with radiotherapy and has activity in other squamous cell carcinomas.
Additional chemotherapy will be given after treatment as neo-adjuvant chemotherapy has not been shown to improve survival when given in combination with radiotherapy in other tumour sites. In addition the toxicity associated with it may impact on the timing of treatment and on the total dose of chemoradiation delivered.
Therefore, the objectives of this trial are as follows:
1. Whether Cisplatin or Mitomycin produces a higher CR rate post treatment
2. Whether Cisplatin or Mitomycin produces a higher grade four acute toxicity
3. Whether maintenance chemotherapy will improve recurrence-free survival
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Anal cancer
Intervention
Four treatment arms:
1. 5-Fluorouracil 1000 mg/m^2, days one to four and 29 to 32 by 24 hour continuous infusion and Mitomycin 12 mg/m^2, day one only, intravenous (iv) bolus and no maintenance therapy
2. 5-Fluorouracil 1000 mg/m^2, days one to four and 29 to 32 by 24 hour continuous infusion and Mitomycin 12 mg/m^2, day one only, iv bolus and maintenance therapy (CDDP)
3. 5-Fluorouracil 1000 mg/m^2, days one to four and 29 to 32 by 24 hour continuous infusion and Cisplatin 60 mg/m^2, days one and 29 by iv infusion and no maintenance therapy
4. 5-Fluorouracil 1000 mg/m^2, days one to four and 29 to 32 by 24 hour continuous infusion and Cisplatin 60 mg/m^2, days one and 29 by iv infusion and maintenance therapy (CDDP)
Maintenance therapy consists of:
Two courses 5-FU and Cisplatin, four weeks after the end of primary chemoradiation repeated after three weeks:
5-Fluorouracil 1000 mg/m^2, days one to four and Cisplatin 60 mg/m^2, day one by iv infusion
Intervention type
Drug
Phase
Phase II
Drug names
5-Fluorouracil, Mitomycin and Cisplatin
Primary outcome measure
1. CR rate (at six months):
1.1. 90% to detect an increase from 80% to 90%
1.2. 95% to detect an increase from 85% to 95%
2. Grade four toxicity: 95% to detect a doubling of the 11% Grade four acute toxicity reported in ACT I
3. Recurrence-free survival:
3.1. 80% to detect 11% difference (64% to 75%)
3.2. 99% to detect 16% difference (64% to 80%)
Secondary outcome measures
Not provided at time of registration
Overall trial start date
01/02/2001
Overall trial end date
31/08/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histological proof of epidermoid anal carcinoma (includes squamous, basaloid and cloacogenic lesions)
2. Patients fit to receive platinum or mitomycin C based chemotherapy determined by:
2.1. Adequate baseline renal function
2.2. Acceptable haematological parameters
2.3. Liver Function Tests (LFTs) within 2 x normal range
2.4. Adequate cardiac function
2.5. No serious uncontrolled medical conditions (particularly cardiovascular disease)
2.6. Written informed consent
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
600
Participant exclusion criteria
1. Anal cancer that has spread to another part of the body
2. Adenocarcinoma or muco-epidermoid anal cancer
3. Lymphoma or melanoma of the anal canal
4. Pre-cancerous cell changes (intraepithelial neoplasia) that have not developed into anal cancer
5. Had your cancer completely removed with an operation
6. Already had treatment for your anal cancer
7. Had radiotherapy to your pelvic area before
8. Had any other cancer in the past
9. Any other serious medical condition
Recruitment start date
01/02/2001
Recruitment end date
31/08/2007
Locations
Countries of recruitment
United Kingdom
Trial participating centre
MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom
Sponsor information
Organisation
Cancer Research UK (CRUK) (UK)
Sponsor details
PO Box 123
Lincoln's Inn Fields
London
WC2A 3PX
United Kingdom
+44 (0)207 317 5186
kate.law@cancer.org.uk
Sponsor type
Charity
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24827136
2017 post-hoc analysis results in: http://www.ncbi.nlm.nih.gov/pubmed/28209296
Publication citations
-
Results
Glynne-Jones R, Kadalayil L, Meadows HM, Cunningham D, Samuel L, Geh JI, Lowdell C, James R, Beare S, Begum R, Ledermann JA, Sebag-Montefiore D, , Tumour- and treatment-related colostomy rates following mitomycin C or cisplatin chemoradiation with or without maintenance chemotherapy in squamous cell carcinoma of the anus in the ACT II trial., Ann. Oncol., 2014, 25, 8, 1616-1622, doi: 10.1093/annonc/mdu188.