Condition category
Cancer
Date applied
31/05/2001
Date assigned
31/05/2001
Last edited
28/07/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr - -

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00025090

Protocol/serial number

ACT II

Study information

Scientific title

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

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 measures

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

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

UKCCCR Register Co-ordinator
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

http://www.cancer.org.uk

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

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24827136

Publication citations

  1. 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.

Additional files

Editorial Notes