An International Multicentre Open Label Randomised Phase II Advanced Anal Cancer Trial Comparing Cisplatin plus 5-fluorouracil versus Carboplatin plus Weekly Paclitaxel in Patients with Inoperable Locally Recurrent or Metastatic Disease

Phase 2

Completed

• Conditions: Squamous Cell Carcinoma of the Anus; Cancer - Bowel - Anal

• Registration Number: ACTRN12616000061437
• Lead Sponsor: Australasian Gastro-Intestinal Trials Group (AGITG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-01-21
• Study Completion: 2018-03-30
• Last Update Posted: 16 March 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 91

Inclusion Criteria

Inoperable, locally recurrent or metastatic disease (tumour resectability should be assessed by a local surgeon or Multidisciplinary Team)
-Histological or cytological confirmation of epidermoid anal carcinoma (includes squamous, basaloid and cloacogenic lesions) from the primary tumour or a newly diagnosed recurrent/metastatic lesion.
-Age greater than or equal to 18 years.
-ECOG PS less than or equal to 2.
-Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1.
-Previous definitive chemo-radiation is permitted for early stage tumours (cisplatin-based chemo-radiation is permitted but only if tumour progression/relapse occurs after 6 months from treatment completion).
-Previous systemic chemotherapy is permitted if administered as induction treatment (less than or equal to 2 cycles) before definitive chemoradiotherapy for early stage disease and there is no evidence of tumour progression during or after treatment completion.
-HIV positive patients will be considered eligible if they are on HAART and have a CD4 count of greater than or equal to 200/microlitre (HIV+ patients who are on HAART and have a CD4 count less than 200/microlitre are eligible if the plasma viral load is below the level of detection according to the local assay).
-Adequate cardiac and respiratory function; absolute neutrophil count (ANC) greater than or equal to 1.5x109/l; platelets greater than or equal to 100x109/l; haemoglobin (Hb) greater than or equal to 9g/dl for males and greater than or equal to 8g/dl for females; creatinine clearance greater than or equal to 50ml/minute; serum bilirubin less than or equal to 1.5x upper limit of normal (ULN); alanine transaminase (ALT) or aspartate transaminase (AST) less than or equal 3x ULN (If liver metastases are present, serum transaminases less than or equal 5x ULN are permitted.
-Fertile men and women must agree to take adequate contraceptive precautions during, and for at least six months after therapy.
-Life expectancy of at least 3 months.

Exclusion Criteria

-Tumours of adenocarcinoma, melanoma, small cell and basal cell histology are excluded.
-Newly diagnosed locally advanced tumour which requires upfront systemic chemotherapy but is still amenable to curative treatment (i.e. chemotherapy followed by definitive chemoradiotherapy)
-Locally recurrent tumour which is amenable to curative resection (as deemed by a local surgeon or Multidisciplinary Team).
-Tumour relapse/progression within 6 months of completion of a cisplatin-based chemoradiotherapy regimen for the treatment of early stage tumours.
-Previous administration of greater than 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease.
Tumour progression during or immediately after completion of less than or equal to 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease.
-Previous use of systemic chemotherapy or other investigational drugs for the treatment of inoperable locally recurrent or metastatic tumours (previous use of radiotherapy in this setting is not an exclusion criterion if: 1) non-irradiated target tumour lesions are present at randomisation for the purpose of tumour response assessment or 2) in the absence of non-irradiated target tumour lesions, progression of the irradiated tumour lesions according to the RECIST criteria version 1.1 is documented).
-Current or recent (within 30 days of first study dosing) treatment with another investigational drug or participation in another investigational study.
-Documented or symptomatic brain metastases and/or central nervous system metastases or leptomeningeal disease.
-Major surgery performed less than 28 days from treatment start.
-Palliative radiotherapy completed less than or equal to 7 days from treatment start.
-Clinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary artery disease, uncontrolled cardiac arrhythmia, or myocardial infarction within the last 6 months). Any history of clinically significant cardiac failure.
- History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan.
- HIV positive patients who are not on HAART or have a CD4 count of less than 200/microlitre in the presence of detectable plasma viral load according to the local assay.
-Known history of active hepatitis B or hepatitis C infection.
-Serious active infection requiring i.v. antibiotics at enrolment.
-Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
-Other clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this trial.
-Known hypersensitivity to any of the study drugs or excipients.
-Known peripheral neuropathy greater than grade 1 (absence of deep tendon reflexes as thesole neurological abnormality does not render the patient ineligible).
-Pre-existing hearing impairment.
-Patients planning for a live vaccine.
-Pregnant or lactating females.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate best overall response rate (ORR) by 24 weeks post treatment in the cisplatin plus 5-fluorouracil (5-FU) arm versus the carboplatin plus weekly paclitaxel arm[Best overall response rate is defined as the percentage of patients achieving confirmed partial or complete responses as per RECIST v1.1 by 24 weeks post treatment start in the modified intention to treat population]