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

NCT01671488 | Terminated Phase 1 Results DMC

• 1 other identifier: BrUOG 276
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

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.

Conditions

Anal Cancer

Keywords

Anal Cancer; Mitomycin; 5-Fluorouracil; 5-FU; IMRT; ADXS11-001

Outcome Measures

Primary Outcomes (2)

• To Evaluate the Safety of the Addition of ADXS11-001 to Standard Chemoradiation for Patients With Anal Cancer.

  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.

  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.

• To Evaluate the 6-month Clinical Complete Response Rate for Patients With Anal Cancer Treated With ADXS11-001 Mitomycin, 5-FU and IMRT.

  Patients to undergo tumor evaluation assessment (via sigmoidoscopy, proctoscopy, colonoscopy or anoscope) 6 months post the start of chemotherapy/radiation.

  Tumor evaluation 6 months after coming off study

Secondary Outcomes (1)

• To Evaluate Progression-free and Overall Survival for Patients With Anal Cancer Treated With ADXS11-001, Mitomycin, 5-FU and IMRT.

  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

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Biological: Treatment; Drug: 5FU; Drug: Mitomycin; Radiation: IMRT

Interventions

Treatment BIOLOGICAL

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.

Also known as: ADXS11-001

Treatment

5FU DRUG

1 gm/m2/day x 96 hours beginning on day 1-4 and day 29-32 + 7 days

Treatment

Mitomycin DRUG

10 mg/m2, day 1 and 29 (day 29 can be + 7 days)

Treatment

IMRT RADIATION

54 Gy in 30 fractions at 1.8 Gy per fraction.

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-proven, invasive primary squamous, basaloid, or cloacogenic carcinoma of the anal canal; 3.1.2 AJCC 2009 TN Stage: T1N1-N3, T2(\< 4cm)N1-N3, T2(\> 4cm)N0,T3N0-3, T4N0-3;based upon the following minimum diagnostic workup: 3.1.2.1 History/physical examination within 14 days prior to registration; 3.1.2.2 Within 42 days prior to registration, the patient must have an anal examination by any of the following: colonoscopy, sigmoidoscopy, or rigid proctoscopy, with documentation of primary anal lesion size, distance from anal verge.
• Groin examination within 42 days prior to registration with documentation of any groin adenopathy and lymphadenopathy (location: right vs. left; medial vs. lateral; mobile vs. fixed; and size); 3.1.4 X-ray (PA and lateral), CT scan, or PET/CT scan of the chest within 42 days prior to registration; 3.1.5 CT scan, MRI, or PET/CT of the abdomen and pelvis within 42 days prior to registration; 3.1.6 Zubrod Performance Status 0-1; 3.1.7 Age ≥ 18; 3.1.8 Laboratory data obtained ≤ 14 days prior to registration on study, with adequate bone marrow, hepatic and renal function defined as follows:
• 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.
• Patients must sign a study-specific informed consent prior to study entry.
• 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.
• 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.
• Patients must be able to swallow pills.

You may not qualify if:

• Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years; 3.2.2 Prior systemic chemotherapy for anal cancer; 3.2.3 Prior allergic reaction to the study drugs involved in this protocol. 3.2.4 Prior radiotherapy to the pelvis that would result in overlap of radiation therapy fields; 3.2.5 Severe, active co-morbidity, defined as follows: 3.2.5.1 Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris and cardiac arrhythmia are ineligible. Furthermore, patients with unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months are ineligible; 3.2.5.2 Patients with active infection requiring systemic therapy (oral or IV) or those currently receiving antibiotics that cannot discontinue prior to dosing are ineligible.
• Transmural myocardial infarction within the last 6 months; 3.2.5.4 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; 3.2.5.5 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; 3.2.5.6 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; 3.2.6 Patients known to be seropositive for HIV and/or active hepatitis, even if liver function studies are in the eligible range.
• Other immunocompromised status (e.g., organ transplant or chronic glucocorticoid use).If patient has diagnosis of immunodeficiency, is dependent on or has received systemic steroids therapy or any form of immunosuppressive therapy within 7 days prior to the first dose of ADXS11-001 they are ineligible. Topical corticosteroid or occasional inhaled corticosteroids are allowed.
• Women who are pregnant or lactating are ineligible because the treatment involved in this study may be significantly teratogenic and there is the potential for transmission of listeria to the infant.
• Patients allergic to or with a sensitivity to penicillin, ampicillin, trimethoprim-sulfa and quinolones (including history of rash or anaphylaxis).
• Patients allergic to naproxen. 3.2.11 Patients receiving oral or IV antibiotics 3.2.12 Patients with a prior history of a splenectomy and/or sickle cell trait/disease 3.2.13 Patient has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants and venous access devices (e.g. Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device and/or implant. Site is required to submit to BrUOG ALL surgical implants patient has ever had in their medical history and ALL surgeries regardless of link to this cancer diagnosis.
• Patients who are receiving or may receive future treatment with PI3K or TNFα inhibitors. To be confirmed by treating medical oncologist in writing 3.2.15 Has undergone a major surgery, including surgery for a new artificial implant and/or device, within 6 weeks prior to the initiation of ADXS11-001 treatment. NOTE: if patient underwent surgery \> 6 weeks from start of ADSX11-001, all toxicities and/or complications must have recovered to baseline or Grade 1 prior to the initiation of ADXS11-001 study therapy.
• Patient not being willing to have new infusion line placed for each infusion of ADXS11-001 as existing or newly placed central venous catheter or infusion ports are not allowed to be used for ADXS11-001 administration. Must be confirmed as discussed with patient and that they agreed.
• Patient not willing to comply with requirement of central venous catheter or infusion port must not be used for 72 hours following the completion of the ADXS11-001 infusion and the patient receives the first post-treatment dose of oral antibiotics. Must be confirmed as discussed with patient and that they agreed.
• Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed. All recent vaccines (within 30 days) to be listed on conmed log 3.2.19 Patient has a history of listeriosis or prior ADXS11-001 therapy.

Sponsors & Collaborators

• Brown University: lead
• Rhode Island Hospital: collaborator
• The Miriam Hospital: collaborator

Study Sites (3)

Montefiore Medical Center

New York, New York, 10467, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

MeSH Terms

Conditions

Anus Neoplasms

Interventions

Therapeutics; Fluorouracil; Mitomycin

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Howard Safran, MD
• Organization: Brown University Oncology Research Group (BrUOG)

kayla_rosati@brown.edu

4018633000

Study Officials

• Howard Safran, MD

  Brown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 23, 2012
• Study Start: February 1, 2013
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: February 17, 2020
• Results First Posted: May 12, 2017

Record last verified: 2020-02

Locations

US (3)