Vectibix for the Treatment of Anal Cancer (VITAL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Grupo Espanol Multidisciplinario del Cancer Digestivo
Sponsor:
Collaborators:
Amgen
Trial Form Support S.L.
Information provided by (Responsible Party):
Grupo Espanol Multidisciplinario del Cancer Digestivo
ClinicalTrials.gov Identifier:
NCT01285778
First received: January 20, 2011
Last updated: September 16, 2013
Last verified: September 2013
  Purpose

Chemoradiation with 5-FU and Mitomycin C is the standard treatment in anal canal SCC. Panitumumab has shown efficacy in other tumors and anti-EGFR treatment has shown clinical activity in a single report of a refractory anal canal SCC patient. Based on this background, we propose to conduct a phase II study to investigate the efficacy and toxicity of radiotherapy with the association:

  • 5-FU 1000mg/m2 on days 1-4 and 29-32
  • Mitomycin C 10mg/m2 on days 1 and 29
  • Panitumumab 6 mg/m2 on day 1, then every 2 weeks for 8 weeks

Condition Intervention Phase
Anal Squamous Cell Carcinoma
Drug: panitumumab, mytomicin C, 5-FU, radiation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Grupo Espanol Multidisciplinario del Cancer Digestivo:

Primary Outcome Measures:
  • Three-year disease-free survival rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Disease free survival rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To assess disease free survival in patients treated with 5-FU, Mytomicin C and Panitumumab concurrently with radiation therapy as treatment for anal squamous cell carcinoma.

  • Three-year free local-regional failure rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To assess three-year free local-regional failure rate in patients treated with 5-FU, Mytomicin C and Panitumumab concurrently with radiation therapy as treatment for anal squamous cell carcinoma.

  • Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To assess overall survival in patients treated with 5-FU, Mytomicin C and Panitumumab concurrently with radiation therapy as treatment for anal squamous cell carcinoma.

  • Colostomy-free survival rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To assess two-year colostomy-free survival rate in patients treated with 5-FU, Mytomicin C and Panitumumab concurrently with radiation therapy as treatment for anal squamous cell carcinoma.

  • Complete response rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To assess complete response rate in patients treated with 5-FU, Mytomicin C and Panitumumab concurrently with radiation therapy as treatment for anal squamous cell carcinoma.

  • Safety profile [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    • Incidence of adverse events (including all serious, grade 3, grade 4, and treatment related events)
    • Changes in laboratory values.

  • Predictive potential of different biomarkers [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    • To investigate the predictive potential of different biomarkers involved in different pathways on efficacy and/or safety endpoints:

      1. EGFR pathway
      2. DNA reparation mechanisms and apoptosis control
      3. Oxidative stress control mechanism
      4. Resistance mechanisms to alkylants (mitomycin C) and antimetabolits (5-FU)
    • To describe the presence of HPV infection, isotype study and impact of the status on efficacy and/or safety.
    • To evaluate the role of magnetic resonance imaging (MRI) in the determination of therapeutic efficacy and follow-up of these patients.


Estimated Enrollment: 58
Study Start Date: October 2010
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panitumumab, mytomicin C, 5-FU, radiation Drug: panitumumab, mytomicin C, 5-FU, radiation

Radiation therapy will be administered concurrent with chemotherapy and Panitumumab treatment. It will start the day 1 of the systemic treatment. That is, the first day of radiation therapy will be the day of the administration of the first dose of Panitumumab and Mitomycin C, as well as the first day of the first 96-hours course of 5-FU continuous infusion. On day 1, drugs and radiation will be administered in the following order:

  • First, Panitumumab. Panitumumab will be administered by IV infusion on day 1, and every 2 weeks during 8 weeks
  • Then Mitomycin C, 10mg/m2 on days 1 and 29
  • Then start the 5-FU continuous infusion, 1000mg/m2 on days 1-4 and 29-32
  • Finally, no less than 2 hours after the start of the 5-FU infusion, first dose of radiation therapy.
Other Name: Vectibix

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ULN
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01285778

Contacts
Contact: Elisabet Molina elisabet.molina@trialformsupport.com

Locations
Spain
Hospital Universitario Germans Trias i Pujol. Institut Català Oncologia Not yet recruiting
Badalona, Barcelona, Spain, 08916
Principal Investigator: Monica Caro, MD         
Consorci Sanitari del Maresme. Hospital de Mataró. Not yet recruiting
Mataró, Barcelona, Spain, 08034
Principal Investigator: Jordi Remon, MD         
Corporació Sanitaria Parc Taulí Active, not recruiting
Sabadell, Barcelona, Spain, 08208
Hospital Infanta Sofía Not yet recruiting
San Sebastian de los Reyes, Madrid, Spain, 28702
Principal Investigator: Miriam López, MD         
Hospital de Navarra Active, not recruiting
Pamplona, Navarra, Spain, 31008
Centro Oncológico de Galicia Active, not recruiting
A Coruña, Spain, 15009
Hospital Santa Creu i Sant Pau Active, not recruiting
Barcelona, Spain, 08041
Hospital Clínic i Provincial Not yet recruiting
Barcelona, Spain, 08036
Principal Investigator: Joan Maurel, MD         
Hospital Universitario Vall Hebron Active, not recruiting
Barcelona, Spain, 08035
Hospital del Mar Active, not recruiting
Barcelona, Spain, 08003
Hospital General Yagüe Active, not recruiting
Burgos, Spain, 09005
Hospital Virgen Blanca Not yet recruiting
León, Spain, 24071
Principal Investigator: Carmen Castañón, MD         
Hospital Universitario La Paz Active, not recruiting
Madrid, Spain, 28046
Hospital Universitario La Princesa Not yet recruiting
Madrid, Spain, 28006
Principal Investigator: Laura Cerezo, MD         
Hospital Universitario Gregorio Marañón Not yet recruiting
Madrid, Spain, 28009
Principal Investigator: Pilar García-Alfonso, MD         
Fundación Jiménez Díaz Active, not recruiting
Madrid, Spain, 28040
Hospital Virgen de la Victoria Not yet recruiting
Málaga, Spain, 29010
Principal Investigator: Isabel Sevilla, MD         
Hospital Universitario de Salamanca Not yet recruiting
Salamanca, Spain, 37007
Principal Investigator: Emilio Fonseca, MD         
Hospital Universitario Marqués de Valdecilla Not yet recruiting
Santander, Spain, 39008
Principal Investigator: Fernando Rivera, MD         
Hospital Universitario Virgen del Rocío Not yet recruiting
Sevilla, Spain, 41013
Principal Investigator: Rocío García-Carbonero, MD         
Hospital General de Valencia Not yet recruiting
Valencia, Spain, 46014
Principal Investigator: Mª José Safont, MD         
Instituto Valenciano de Oncología Recruiting
Valencia, Spain, 46009
Principal Investigator: Carlos Fernandez-Martos, MD         
Hospital de Manises Not yet recruiting
Valencia, Spain, 46940
Principal Investigator: José María Vicent, MD         
Hospital Universitario Miguel Servet Active, not recruiting
Zaragoza, Spain, 50009
Sponsors and Collaborators
Grupo Espanol Multidisciplinario del Cancer Digestivo
Amgen
Trial Form Support S.L.
Investigators
Study Director: Jaime Feliu, MD Hospital Universitario La Paz
Principal Investigator: Vicente Alonso, MD Hospital Universitario Miguel Servet
Principal Investigator: Jaume Capdevila, MD Hospital Universitario Vall Hebron
Principal Investigator: Ruth Vera, MD Hospital de Navarra
Principal Investigator: Miriam Lopez, MD Hospital Infanta Sofia
Principal Investigator: Carmen Castañon, MD Hospital Virgen Blanca (León)
Principal Investigator: Carlos Fernández-Martos, MD Instituto Valenciano de Oncología
Principal Investigator: Manuel Gallén, MD Hospital del Mar, Barcelona
Principal Investigator: Carlos García Girón, MD Hospital General Yagüe (Burgos)
Principal Investigator: Ana León, MD Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Principal Investigator: Marta Martín, MD Hospital de la Santa Creu i Sant Pau de Barcelona
Principal Investigator: Juan Carlos Méndez, MD Centro Oncológico de Galicia
Principal Investigator: Rocío García Carbonero, MD Hospital Universitario Virgen del Rocío (Sevilla)
Principal Investigator: Jordi Remon, MD Hospital de Mataró
Principal Investigator: Fernando Rivera, MD Hospital Universitario Marqués de Valdecilla (Santander)
Principal Investigator: Laura Cerezo, MD Hospital Universitario La Princesa (Madrid)
Principal Investigator: Pilar García-Alfonso, MD Hospital Universitario Gregorio Marañón (Madrid)
Principal Investigator: Emilio Fonseca, MD Hospital Universitario de Salamanca
Principal Investigator: Aleydis Pisa, MD Corporació Sanitaria Parc Taulí (Sabadell, Barcelona)
Principal Investigator: Mónica Caro, MD Institut Català d´Oncologia. Hospital Germans Trias i Pujol (Badalona)
Principal Investigator: José María Vicent, MD Hospital de Manises (Valencia)
Principal Investigator: Isabel Sevilla, MD Hospital Universitario Virgen de la Victoria (Málaga)
Principal Investigator: Joan Maurel, MD Hospital Clinic de Barcelona
Principal Investigator: I Guasch, MD Hospital Sant Joan de Deu
Principal Investigator: Jesus Garcia-Foncillas, MD Clinica Universidad de Navarra
Principal Investigator: Antonio Arrivi, MD Hospital Son Llatzer
  More Information

No publications provided

Responsible Party: Grupo Espanol Multidisciplinario del Cancer Digestivo
ClinicalTrials.gov Identifier: NCT01285778     History of Changes
Other Study ID Numbers: GEMCAD-0902
Study First Received: January 20, 2011
Last Updated: September 16, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Grupo Espanol Multidisciplinario del Cancer Digestivo:
Anal squamous cell carcinoma
panitumumab
chemoradiation
anal cancer
GEMCAD-09-02

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Anus Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Fluorouracil
Antibodies, Monoclonal
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2014