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Phase 2 Trial to Assess the Efficacy and Safety of Chemoradiation With 5-fluorouracil, Mytomicin C and Panitumumab as a Treatment for Anal Squamous Cell Carcinoma

Phase 2
18 Years
Open (Enrolling)
Anal Squamous Cell Carcinoma

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Trial Information

Phase 2 Trial to Assess the Efficacy and Safety of Chemoradiation With 5-fluorouracil, Mytomicin C and Panitumumab as a Treatment for Anal Squamous Cell Carcinoma

In the 1980s, the treatment of choice for anal cancer was abdominal-perineal amputation,
which included the removal of the anus, rectum and lymphatic drainage areas and a permanent
colostomy. With this treatment, 5-year survival rates were 40-70%. In the following years,
however, it was shown that anal cancer was a tumor that was sensitive to chemotherapy and
radiation, so surgery was not the first choice and was only reserved for resistant cases or
relapses. Concomitant chemo and radiotherapy based on the Mitomycin C - 5-FU regimen is
currently the standard treatment for localized (except T1N0) and locally advanced cases.
This statement is supported by two randomized studies that showed that the administration of
chemoradiation with Mitomycin C - 5FU was better than radiation in monotherapy. The trial
conducted by the United Kingdom Coordinating Committee on Cancer Research (UKCCCR)
randomized 585 patients to receive radiotherapy (45 Gy in 4-5 weeks) or the same
radiotherapy regimen coupled with 5-FU (1000 mg/m2 x 4 days or 750 mg/m2 x 5 days), for the
first and last week of radiotherapy and Mitomycin C 12 mg/m2 on day 1. The 3-year local
failure rate was 39% in the combined arm versus 61% with radiotherapy alone. There were no
differences in the 3-year overall survival rate. On the other hand, in the study conducted
by EORTC, 110 patients were distributed to receive radiotherapy (45 Gy in 5 weeks, with an
overimpression of 15 Gy in the patients with CR and 20 Gy if PR) or radiotherapy plus 5-FU
(750 mg/m2 days 1-5 and 29-33) associated to Mitomycin C (15 mg/m2 on day 1). The CR rate
was significantly greater in the group treated with chemoradiation (80% vs. 54%). After 5
years of follow-up, there was still an 18% increase in the local control rate in favor of
the group treated with chemoradiation.

More recently, the results of a phase II CALGB trial, suggests that the administration of
induction treatment with two cycles of cisplatin-5FU (cisplatin 100 mg/m2 on days 1 and 29
and 5FU 1000 mg/m2 days 1-4 and 29-32) followed by chemoradiotherapy with 5-FU and
Mitomycin C was very promising, especially in patients with a poor prognosis, with 50% of
patients remaining colostomy and disease-free at 48 months. However, in a randomized study
by the RTOG group, which included 682 patients, this strategy was compared with the classic
concomitant chemoradiation with 5-FU (1000 mg/m2 days 1-4 and 29-32) and Mitomycin C (10
mg/m2 days 1 and 29). No differences in survival were found, but it was also detected that
the colostomy rate was greater in the patients treated with the regimen containing Cisplatin
(HR, 1.68; 95% CI, 1.07-2.65; P=.02). The authors concluded that induction with cisplatin
was not superior to the traditional administration of 5FU-Mitomycin C with RT.

Epidermoid anal cancer is a tumor that often expresses the EGFR receptor. In an initial
study with 21 cases, it was reported that there was EGFR expression in all the biopsies. In
another study with 38 cases, it was found that 55% of the tumors expressed EGFR. No study
has been published, however, which has investigated the efficacy of Panitumumab in this
tumor. There is only one report of a refractory case in which cetuximab was administered
together with CPT-11 with an excellent response.

Inclusion Criteria:

- Man or woman ≥ 18 years

- Competent to comprehend, sign, and date an IEC-approved informed consent form

- Histologically or cytologically-confirmed anal canal SCC

- T status 2-4 and any N status (pelvic or inguinal) radiologically defined by MRI

- De novo diagnosis of anal canal SCC not previously treated

- ECOG performance status of 0, 1 or 2

- If a subject has prior history of cancer other than anal canal SCC, non-melanoma skin
carcinoma, or in situ cervical carcinoma, then the subject should neither have
received any treatment nor have shown any signs of active disease within the previous
5 years

- Adequate bone marrow function: neutrophils≥1.5 x109/ L; platelets≥100 x109/ L;
hemoglobin≥ 9 g/ dL

- Hepatic function as follows: total bilirubin count ≤ 1.5 x ULN; ALT and AST ≤ 2.5 x

- Calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min

- Magnesium≥ lower limit of normal

Exclusion Criteria:

- Metastatic anal canal SCC

- HIV infection (except patients with an undetectable viral load and CD4 cells count
>400/mL which are eligible for the study)

- Known hypersensitivity to any of the study drugs

- Evidence of any other disease, metabolic dysfunction, physical examination finding or
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or puts the patient at high risk
for treatment-related complications

- Patients they have received prior systemic therapy or radiotherapy for the treatment
of SCC anal carcinoma.

- Prior malignant tumor in the last 5 years, except a history of non-melanoma skin
carcinoma, or in situ cervical carcinoma.

- Clinically significant cardiovascular disease, for example myocardial infarction (< 6
months before treatment start), unstable angina, congestive heart failure, arrhythmia
requiring medication, or uncontrolled hypertension

- Known positive test for, hepatitis C virus, chronic active hepatitis B infection

- Any kind of disorder that compromises the ability of the subject to give written
informed consent and/or comply with the study procedures

- Any investigational agent within 30 days before enrolment

- Subject who is pregnant or breast feeding

- Surgery (excluding diagnostic biopsy or central venous catheter placement) and/or
radiotherapy within 28 days prior to inclusion in the study.

- Woman or man of childbearing potential not consenting to use adequate contraceptive
precautions i.e. double barrier contraceptive methods (eg diaphragm plus condom), or
abstinence during the course of the study and for 6 months after the last study drug
administration for women, and 3 month for men

- Psychological, familial, sociological, or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; those conditions
should be discussed with the patient before registration in the trial.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Three-year disease-free survival rate

Outcome Description:

To estimate the three-year disease-free survival rate in patients treated with 5-FU, mytomicin C and Panitumumab concurrently with radiation therapy as treatment for anal squamous cell carcinoma

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Jaime Feliu, MD

Investigator Role:

Study Director

Investigator Affiliation:

Hospital Universitario La Paz


Spain: Spanish Agency of Medicines

Study ID:




Start Date:

October 2010

Completion Date:

January 2016

Related Keywords:

  • Anal Squamous Cell Carcinoma
  • Anal squamous cell carcinoma
  • panitumumab
  • chemoradiation
  • anal cancer
  • GEMCAD-09-02
  • Anus Neoplasms
  • Carcinoma
  • Carcinoma, Squamous Cell