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

This study has been completed.
Information provided by (Responsible Party):
Ziopharm Identifier:
First received: August 29, 2012
Last updated: January 26, 2015
Last verified: January 2015

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.

Condition Intervention Phase
Breast Cancer Nos Metastatic Recurrent
Genetic: Ad-RTS-hIL-12 and Veledimex
Drug: Palifosfamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Ziopharm:

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

Secondary Outcome Measures:
  • Objective response rate (ORR) by modified RECIST v1.1 [ Time Frame: Approximately 24 weeks- From first study drug dose to Follow-Up Tumor Assessment Visit ]
    Proportion of subjects achieving a confirmed PR or CR according to modified RECIST v1.1

  • Clinical Benefit rate: proportion of subjects with CR, PR, or SD by modified RECIST v1.1 [ Time Frame: Approximately 24 weeks ]
  • Estimate PFS by modified RECIST v1.1 [ Time Frame: 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 [ Time Frame: Approximately 24 weeks, starting with first study drug administrationa and ending at the Follow up Tumor Assessment visit ]

Enrollment: 12
Study Start Date: March 2013
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Pali

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01703754

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

Responsible Party: Ziopharm Identifier: NCT01703754     History of Changes
Other Study ID Numbers: ATI001-201
Study First Received: August 29, 2012
Last Updated: January 26, 2015

Keywords provided by Ziopharm:
Genetically Modified Organism
Metastatic Breast Cancer
Recurrent Breast Cancer
Breast Cancer
Adenoviral vector

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Isophosphamide mustard
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents processed this record on April 24, 2017