Clinical Trial: A Phase I/II Evaluation of ADXS11-001, Mitomycin, 5-fluorouracil (5-FU) and IMRT for Anal Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: BrUOG 276: A Phase I/II Evaluation of ADXS11-001, Mitomycin,5-fluorouracil (5-FU) and IMRT for Anal Cancer

Brief Summary: The main purpose of this study is to study the safety and effectiveness of ADXS11-001 when combined with standard chemotherapy and radiation treatment for anal cancer. ADXS11-001 is an investigational agent that is not approved by the FDA to treat anal cancer or any other cancer.

Detailed Summary:

Novel treatments are needed in anal cancer. An important percentage of patients with locally advanced anal cancer will have persistent loco-regional disease or develop systemic metastases. Virtually all cases of anal cancer are related to infection by HPV. Anal cancer cells infected with HPV have the tumor associated antigen HPV E7. ADXS11-001 causes antigen presenting cells to be stimulated to facilitate immune cells to attack cancer cells expressing HPV E7. ADXS11-001, at the phase II dose of 1x109 CFU, has been shown to be safe in patients with advanced cervical cancer which also is caused by HPV infection. Anti-tumor activity and safety have been demonstrated in cervical cancer to single agent ADXS11-001 and the combination of ADXS11-001 and cisplatin chemotherapy. Data presented at ASCO 2012 ADXS11-001 is currently being evaluated in women in the United States with cervical intraepithelial neoplasia. Radiation may augment the activity of ADXS11-001 increasing the exposure of tumor related antigens thereby increasing the chance for loco-regional disease eradication and preventing systemic recurrence. Therefore, ADXS11-001 may increase complete response, prevent recurrence disease and increase disease-free and overall survival in anal cancer. This protocol will develop sufficient preliminary safety and efficacy data to facilitate the investigation of ADXS11-001 in anal cancer within "NRG", the newly formed cooperative group based on the merger of the RTOG, NSABP and GOG.

As described above, Phase I studies and preliminary data from phase II studies have demonstrated that ADXS11-001, 1x109 CFU, can be safely administered as a single agent and in combination with chemotherapy. For example in over 200 patients treated at the dose of 1x109CFU there have been no cases of severe listeria bacteremia or grade 3 cardiopulmonary toxicity. However, since ADXS11-001 has
Sponsor: Brown University

Current Primary Outcome:

  • To Evaluate the Safety of the Addition of ADXS11-001 to Standard Chemoradiation for Patients With Anal Cancer. [ Time Frame: Baseline, then prior to each ADXS11-001 and weekly during radiation. Assessments 1-2 weeks post radiation then 2-6 weeks post vaccine and off study and 30 days post treatment. ]
    Evaluate maximal toxicities via CTCAE version 4.0 All adverse events, serious and non-serious, were captured from date of ICF through 4 weeks post treatment completion- regardless of causality.
  • To Evaluate the 6-month Clinical Complete Response Rate for Patients With Anal Cancer Treated With ADXS11-001 Mitomycin, 5-FU and IMRT. [ Time Frame: Tumor evaluation 6 months after coming off study ]
    Patients to undergo tumor evaluation assessment (via sigmoidoscopy, proctoscopy, colonoscopy or anoscope) 6 months post the start of chemotherapy/radiation.


Original Primary Outcome:

  • To evaluate number of adverse events with the addition of ADXS11-001 to standard chemoradiation for patients with anal cancer. [ Time Frame: Every week during treatment, for an average of 6 months. Once off study annually, for an average of 5 years. ]
  • To Evaluate the 6-month Clinical Complete Response Rate for Patients With Anal Cancer Treated With ADXS11-001 Mitomycin, 5-FU and IMRT. [ Time Frame: Tumor evaluation 6 months after coming off study ]


Current Secondary Outcome: To Evaluate Progression-free and Overall Survival for Patients With Anal Cancer Treated With ADXS11-001, Mitomycin, 5-FU and IMRT. [ Time Frame: Follow up and survival status at 6 months and 1 year post coming off study and annually until patient has been off for 5 years ]

Patients terminating study treatment early prior to disease recurrence will be followed every 6 months for year 1 then annually for a total of 5 years. The follow-up portion will commence once patient comes off study or post the 2-6 week post the 4th treatment time point/visit.

Assessments were tumor evaluation via sigmoidoscopy, proctoscopy, colonoscopy or anoscope and also chest/abdomen/pelvic imaging.



Original Secondary Outcome:

  • To Evaluate Progression-free and Overall Survival for Patients With Anal Cancer Treated With ADXS11-001, Mitomycin, 5-FU and IMRT. [ Time Frame: Follow up and survival status at 6 months and 1 year post coming off study and annually until patient has been off for 5 years ]
  • To assess peripheral and histologic markers of immune response including measuring immunohistochemistry of biopsies for T cell infiltration, following ADXS11-001 in patients [ Time Frame: Prior to study procedures, within 3 days of beginning radiation and 6 months after coming off study therapy ]


Information By: Brown University

Dates:
Date Received: August 7, 2012
Date Started: April 2013
Date Completion: May 2018
Last Updated: April 4, 2017
Last Verified: April 2017