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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ziopharm
ClinicalTrials.gov Identifier:
NCT01703754
First received: August 29, 2012
Last updated: January 26, 2015
Last verified: January 2015

August 29, 2012
January 26, 2015
March 2013
December 2014   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of study drug therapy based on type and rate of adverse events occurring in the treatment population [ Time Frame: Approximately 24 weeks-Beginning from the time a patient signs the informed consent to the Post Treatment Safety Visit ] [ Designated as safety issue: Yes ]
  • 12-week PFS rate, calculated as the number of subjects who had not progressed or died prior to 12 weeks from the date of their first dose, divided by the number of subjects in the study arm. [ Time Frame: 12 weeks, starting at the date the first dose of study drug is administered ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01703754 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Objective response rate (ORR) by RECIST v1.1 and/or immune related response criteria (irRC): [ Time Frame: Approximately 24 weeks- From first study drug dose to Follow-Up Tumor Assessment Visit ] [ Designated as safety issue: No ]
    Proportion of subjects achieving a confirmed PR or CR according to RECIST v1.1 or irRC during study.
  • Clinical Benefit rate: proportion of subjects with CR, PR, or SD by RECIST v1.1 and/or irRC [ Time Frame: Approximately 24 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer Nos Metastatic Recurrent
  • 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
  • Experimental: Ad-RTS-hIL-12 and veledimex
    Experimental study drug monotherapy arm (A)
    Intervention: Genetic: Ad-RTS-hIL-12 and Veledimex
  • Experimental: Ad-RTS-hIL-12 and Palifosfamide
    Study drug combination therapy arm (C)
    Interventions:
    • Genetic: Ad-RTS-hIL-12 and Veledimex
    • Drug: Palifosfamide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
December 2014
December 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01703754
ATI001-201
No
Ziopharm
Ziopharm
Not Provided
Study Director: Francois Lebel, MD ZIOPHARM Oncology
Ziopharm
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP