A Phase I/II Evaluation of ADXS11-001, Mitomycin, 5-fluorouracil (5-FU) and IMRT for Anal Cancer (276)
|Anal Cancer||Biological: Treatment Drug: 5FU Drug: Mitomycin Radiation: IMRT||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||BrUOG 276: A Phase I/II Evaluation of ADXS11-001, Mitomycin,5-fluorouracil (5-FU) and IMRT for Anal Cancer|
- 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.
- 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.
|Actual Study Start Date:||February 2013|
|Estimated Study Completion Date:||February 2018|
|Estimated Primary Completion Date:||February 2018 (Final data collection date for primary outcome measure)|
The first dose will be given 10-14 days prior to the initiation of chemoradiation.
Patient will then receive 5-FU: 1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days and Mitomycin: 10 mg/m2, day 1 and 29 with IMRT radiation: 54 Gy in 30 fractions at 1.8 Gy per fraction.
The 2-4th dosages of ADXS11-001 will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals.
ADXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 4 total doses. All 4 doses of ADXS11-001 will be 1x109 cfu.
Other Name: ADXS11-001Drug: 5FU
1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 daysDrug: Mitomycin
10 mg/m2, day 1 and 29 (day 29 can be + 7 days)Radiation: IMRT
54 Gy in 30 fractions at 1.8 Gy per fraction.
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 not previously been administered with radiation, the primary objective of this study will be to establish the safety of the addition of ADXS11-001 to chemoradiation for anal cancer. The following schedules will be assessed.
• Treatment Schedule: The first dose will be given 10-14 days prior to the initiation of chemoradiation. The 2nd-4th dosages of ADXS11-001will not be until after completion of all chemoradiation. The second dosage of ADXS11-001 will not be administered until a minimum of 10 days after completion of chemoradiation, ANC > 1,000 cells/mm3, serum creatinine < 1.5 mg/dl and all toxicities from chemoradiation have resolved to grade 2 or less. The subsequent third and fourth treatment with of ADXS11 will be administered at 28 day intervals. This will provide the needed safety data to evaluate Treatment Schedule #2.
Standard treatment with mitomycin, 5-FU and radiation for anal cancer has substantial toxicity. In RTOG 9811, 74% of patients had grade 3/4 nonhematologic toxicity and 61% of patients had grade 3 or grade 4 hematologic toxicity from this regimen. Therefore, the toxicities of standard chemoradiation with mitomycin, 5-FU and radiation are well above the conventionally accepted parameters in a phase I study even prior to adding ADXS11-001. However, it is critical that the addition of ADXS-11-001 does not compromise the delivery of potentially curative standard chemoradiation for anal cancer.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01671488
|United States, New York|
|Montefiore Medical Center|
|New York, New York, United States, 10467|
|United States, Rhode Island|
|Rhode Island Hospital|
|Providence, Rhode Island, United States, 02903|
|The Miriam Hospital|
|Providence, Rhode Island, United States, 02906|
|Principal Investigator:||Howard Safran, MD||Brown University Oncology Research Group|