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

Phase 2

Completed

• Conditions: Breast Cancer Nos Metastatic Recurrent
• Interventions: Genetic: Ad-RTS-hIL-12 and Veledimex; Drug: Palifosfamide

• Registration Number: NCT01703754
• Lead Sponsor: Alaunos Therapeutics

Brief Summary

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.

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 Timeline

• Study First Submitted: 2012-08-29
• Study First Submitted QC: 2012-10-09
• Study First Posted: 2012-10-10
• Study Start: 2013-03
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Status Verified: 2015-01
• Last Update Submitted: 2015-01-26
• Last Update Posted: 2015-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ad-RTS-hIL-12 and veledimex	Ad-RTS-hIL-12 and Veledimex	Experimental study drug monotherapy arm (A)
Ad-RTS-hIL-12 and Palifosfamide	Ad-RTS-hIL-12 and Veledimex	Study drug combination therapy arm (C)
Ad-RTS-hIL-12 and Palifosfamide	Palifosfamide	Study drug combination therapy arm (C)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Objective response rate (ORR) by modified RECIST v1.1	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
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

Trial Locations

Locations (8)

Baptist Cancer Institute; 🇺🇸 Jacksonville, Florida, United States

Billings Clinic; 🇺🇸 Billings, Montana, United States

Signal Point Clinical Research Center; 🇺🇸 Middletown, Ohio, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Greenville Hospital System; 🇺🇸 Greenville, South Carolina, United States

The Jones Clinic, PC; 🇺🇸 Germantown, Tennessee, United States

Evergreen Hematology & Oncology; 🇺🇸 Spokane, Washington, United States

Mary Crowley Medical Research Center; 🇺🇸 Dallas, Texas, United States