Overview

This trial is active, not recruiting.

Condition anal cancer
Treatment advaxis
Phase phase 1/phase 2
Sponsor Brown University
Collaborator Rhode Island Hospital
Start date April 2013
End date December 2017
Trial size 25 participants
Trial identifier NCT01671488, BrUOG 276

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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Treatment Schedule #1: The first dose will be given 10-14 days prior to the initiation of chemoradiation. 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, ANC > 1,000 cells/mm3, Platelets ≥ 50,000 cells/mm3, serum creatinine < 1.5 mg/dl and all non-hematologic 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. ADXS11-001 administration may be +/- 72 hours. The second cycle of chemotherapy may be +/- 72 hours.
advaxis ADXS11-001
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. The drug will be given as an 500ml infusion over 15 minutes.
(Experimental)
Schedule #2: Once all patients have completed Schedule #1 and have been observed for 28 days Schedule #2 will proceed. Schedule #2 will investigate the second dose of ADXS11-001 D21 of chemoradiation. Administration on day 21 of chemoradiation would only be administered if ANC > 1,000 cells/mm3, serum creatinine < 1.5mg/dl and all non-heme toxicities were grade 2 or less. The third txt with ADXS11-001 would be no less than 10 days after chemoradiation, if ANC > 1,000 cells/mm3, PLTs ≥ 50,000 cells/mm3, serum creatinine < 1.5mg/dl and all toxicities were grade 2 or less. The fourth txt would be 28 days later. If the second dose in Schedule #2, can't be given on D21 (+/- 72 hrs) then Schedule #1 will be used for the second dose.
advaxis ADXS11-001
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. The drug will be given as an 500ml infusion over 15 minutes.

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria

  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
  • Platelets ≥ 100,000 cells/mm3;
  • Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.);
  • Serum creatinine ≤ 1.5 mg/dl;
  • Bilirubin < 1.4mg/dl;
  • ALT/AST < 3 x ULN;
  • Negative serum pregnancy test for women of child-bearing potential; 3.1.9 Women of childbearing potential and male participants must agree to use a 2 forms of medically effective means of birth control (such as a condom and spermicide) throughout their participation in the treatment phase of the study and for 90 days post last dose of study drug. 3.1.10 Patients must sign a study-specific informed consent prior to study entry. 3.1.11 Patients with a history of clinically significant pulmonary disease must have PFTs demonstrating a DLCO ≥ 40%. This testing is considered standard of care prior to mitomycin, 5-FU and radiation. 3.1.12 Patients with a history of clinically significant cardiac disease must have a LVEF ≥ 30% by ECHO. (MUGA scan may also be used to determine LVEF) This testing is considered standard of care prior to mitomycin, 5-FU and radiation. 3.1.13 Patients must be able to swallow pills.

Exclusion Criteria

    Additional Information

    Official title BrUOG 276: A Phase I/II Evaluation of ADXS11-001, Mitomycin,5-fluorouracil (5-FU) and IMRT for Anal Cancer
    Principal investigator Howard Safran, MD
    Description 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 #1: 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. - Treatment Schedule #2: If dose limiting toxicities (defined below) are not exceeded during Treatment Schedule #1, then Treatment Schedule #2 will investigate administration of the second dose of ADXS11-001 on day 21 of chemoradiation. Administration of ADXS11-001 on day 21 of chemoradiation would only be administered if ANC > 1,000 cells/mm3, serum creatinine < 1.5mg/dl and all toxicities from ongoing chemoradiation were grade 2 or less. The third treatment with ADXS11-001 would be administered no less than 10 days after completion of all chemoradiation, if ANC > 1,000 cells/mm3, serum creatinine < 1.5mg/dl and all toxicities from ongoing chemoradiation were grade 2 or less. The fourth treatment would be 28 days later. 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.
    Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
    Information provided to ClinicalTrials.gov by Brown University.
    Location data was received from the National Cancer Institute and was last updated in June 2016.