A second UK Phase III anal cancer trial: a trial of chemoradiation and maintenance therapy for patients with anal cancer

ISRCTN ISRCTN26715889
DOI https://doi.org/10.1186/ISRCTN26715889
ClinicalTrials.gov (NCT) NCT00025090
Protocol serial number ACT II
Sponsor Cancer Research UK (CRUK) (UK)
Funder Cancer Research UK (CRUK) (UK)
Submission date
31/05/2001
Registration date
31/05/2001
Last edited
17/10/2018
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr - -
Scientific

UKCCCR Register Co-ordinator
MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom

Study information

Primary study designInterventional
Study designRandomised controlled trial
Secondary study designRandomised controlled trial
Study type Participant information sheet
Scientific titleA second UK Phase III anal cancer trial: a trial of chemoradiation and maintenance therapy for patients with anal cancer
Study acronymACT II
Study objectivesFollowing 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(s)Not provided at time of registration
Health condition(s) or problem(s) studiedAnal cancer
InterventionFour 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 typeDrug
PhasePhase II
Drug / device / biological / vaccine name(s)5-Fluorouracil, Mitomycin and Cisplatin
Primary outcome measure(s)

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%)

Key secondary outcome measure(s)

Not provided at time of registration

Completion date31/08/2007

Eligibility

Participant type(s)Patient
Age groupNot Specified
Sex
Target sample size at registration600
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment01/02/2001
Date of final enrolment31/08/2007

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centre

MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/08/2014 Yes No
Results article post-hoc analysis results 01/03/2017 Yes No
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
Plain English results No Yes

Editorial Notes

17/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
20/02/2017: Publication reference added.

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