Adenoviral Vector Monotherapy or Combination With Chemotherapy in Subjects With Recurrent/Metastatic Breast Cancer.

A Phase II Randomized, Open Label Study of Ad-RTS-hIL-12 Monotherapy or Combination With Palifosfamide in Subjects With Recurrent/Metastatic Breast Cancer and Accessible Lesions

Phase II, randomized, safety and efficacy study in recurrent/metastatic breast cancer with accessible lesions.

Primary End point is rate of Progression Free Survival (PFS) at the 16 week treatment time point. Hypothesis: Adenoviral vector (Ad-RTS-hIL-12) alone and in combination with chemotherapy (palifosfamide) is safe and efficacious.

Study Overview

• Status: Completed
• Conditions: Breast Cancer Nos Metastatic Recurrent
• Intervention / Treatment: Genetic: Ad-RTS-hIL-12 and Veledimex; Drug: Palifosfamide

Detailed Description

Multicenter, open-label, randomized study evaluating the safety and efficacy of INXN-1001 (veledimex) and INXN-2001 (Ad-RTS-hIL-12) alone and in combination with palifosfamide.

Part 1 is the safety run-in where a safety assessment will be made after 1 cycle of therapy.

Part 2, eligible subjects will be randomly assigned to active treatment Arms A or C.

Once the monotherapy (Arm A) is determined to be safe and tolerable, Part 1 combination therapy (Arm C) will begin.

Subjects should receive six cycles of study treatment, in the absence of meeting withdrawal criteria.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • Ohio
    • Middletown, Ohio, United States, 45042
      • Signal Point Clinical Research Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Jones Clinic, PC
  • Texas
    • Dallas, Texas, United States, 75201
      • Mary Crowley Medical Research Center
  • Washington
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology & Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Males or females ≥ 18 years of age
2. Histologically or cytologically confirmed adenocarcinoma of the breast, either locally recurrent or metastatic disease with injectable lesions, for which no proven curative therapy exists.
3. Failed or progressed on at least 1 prior systemic chemotherapy regimen ± biologic/experimental therapy (if first-line therapy, failure or progression during the first 30 days).
4. Resolution of all treatment-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy ≤ Grade 2 and alopecia.
5. A minimum of 2 lesion(s) assessed by imaging using mRECIST v1.1.
6. Eastern Cooperative Oncology Group performance status 0, 1, 2
7. Male and female subjects must agree to use a highly reliable method of birth control.

8. Adequate bone marrow reserve as indicated by:

   1. Absolute neutrophil count > 1500/μL (without use of growth factors within 7 days)
   2. Absolute lymphocyte count > 700/μL (without use of growth factors within 7 days)
   3. Platelet count > 100,000/mm3 (without transfusion in prior 7 days)
   4. Hemoglobin > 9.0 g/dL (without transfusion in prior 7 days)
9. Estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation: eGFR ≥ 60 mL/min/1.73 m2

10. Adequate liver function as evidenced by the following:

    1. Bilirubin ≤ 1.5 times the upper limits of normal (ULN)
    2. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 2.5×ULN, in the case of liver metastases ≤ 5×ULN

Exclusion Criteria:

1. Subjects with human epidermal growth factor receptor 2 (HER2)/neu-positive (immunohistochemistry [IHC]) 3+ or fluorescence in situ hybridization-amplified) breast tumors who are eligible for, but who have not received HER2-targeted therapy (eg, trastuzumab)
2. Concomitant anticancer therapies

3. Prior therapies discontinuation periods:

   1. Radiation within 3 weeks of enrollment
   2. Chemotherapy within 4 weeks of enrollment
   3. Nitrosoureas within 6 weeks of enrollment
   4. Biologic therapy and/or immunomodulatory therapy, checkpoint inhibitors within 6 weeks of enrollment
   5. No washout period is required for endocrine therapy
4. Radiation therapy encompassing >25% of bone marrow
5. History of bone marrow or stem cell transplantation
6. Any congenital or acquired condition leading to inability to generate an immune response

7. Immunosuppressive therapy:

   1. Systemic immunosuppressive drugs including corticosteroids (prednisone equivalent >10 mg/day)
   2. Immune suppression/requiring immunosuppressive drugs, including organ allografts
   3. Active autoimmune disease requiring the equivalent of >10 mg/day of prednisone
8. Major surgery within 4 weeks of study treatment
9. History of prior malignancy, unless the prior malignancy was diagnosed and definitively treated ≥5 years previously with no subsequent evidence of recurrence
10. Subjects with brain or subdural metastases, unless local therapy has completed and corticosteroids have been discontinued for this indication for ≥4 weeks before starting study treatment.
11. Any medications that induce, inhibit, or are substrates of cytochrome P450 (CYP450) 3A4 within 7 days prior to the first dose of study drug
12. Subjects with meningeal carcinomatosis
13. Known significant hypersensitivity to study drugs or excipients
14. History of malabsorption syndrome or other condition that would interfere with enteral absorption
15. International Normalized Ratio (INR) and activated partial thromboplastin time [PTT] <1.5 x ULN, if not therapeutically anticoagulated.
16. New York Heart Association (NYHA) Class II or greater congestive heart failure OR active ventricular arrhythmia requiring medication
17. Any other unstable or clinically significant concurrent medical condition
18. Localized infection at site of injectable lesion(s) requiring antiinfective therapy within 2 weeks of the first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ad-RTS-hIL-12 and veledimex; Experimental study drug monotherapy arm (A)	Genetic: Ad-RTS-hIL-12 and Veledimex; Oral activator ligand with adenoviral vector injection of cancer lesions; Other Names: Adenoviral Vector; Oral activator ligand
Experimental: Ad-RTS-hIL-12 and Palifosfamide; Study drug combination therapy arm (C)	Genetic: Ad-RTS-hIL-12 and Veledimex; Oral activator ligand with adenoviral vector injection of cancer lesions; Other Names: Adenoviral Vector; Oral activator ligand; Drug: Palifosfamide; Small molecule chemotherapy, IV administration; Other Names: Pali

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of study drug therapy based on type and rate of adverse events and 16-week PFS rate.	Approximately 24 weeks-Beginning from the time a patient signs the informed consent to the Follow up Tumor Assessment visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) by modified RECIST v1.1	Proportion of subjects achieving a confirmed PR or CR according to modified RECIST v1.1	Approximately 24 weeks- From first study drug dose to Follow-Up Tumor Assessment Visit
Clinical Benefit rate: proportion of subjects with CR, PR, or SD by modified RECIST v1.1		Approximately 24 weeks
Estimate PFS by modified RECIST v1.1		Approximately 24 weeks, beginning at the first study drug administratrion and ending at the Follow up Tumor Assessment visit
Evaluate Pharmacodynamic tumor markers in tumor tissue samples that may correlate with objective tumor response and/or clinical outcome		Approximately 24 weeks, starting with first study drug administrationa and ending at the Follow up Tumor Assessment visit

Collaborators and Investigators

• Sponsor: Alaunos Therapeutics
• Investigators: Study Director: Francois Lebel, MD, Ziopharm Oncology

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 29, 2012
• First Submitted That Met QC Criteria: October 9, 2012
• First Posted (Estimate): October 10, 2012

Study Record Updates

• Last Update Posted (Estimate): January 27, 2015
• Last Update Submitted That Met QC Criteria: January 26, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Breast Cancer; Metastatic Breast Cancer; Recurrent Breast Cancer; Adenoviral vector; Genetically Modified Organism; Palifosfamide; INXN1001; INXN2001
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Breast Neoplasms; Recurrence; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Ifosfamide; Isophosphamide mustard
• Other Study ID Numbers: ATI001-201