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Phase 1b' Open Label, Single Arm, Multicenter Trial to Evaluate the Safety, Tolerance, Response Rate and Immunological Effects of Repeated Intratumoral Injections of Adenoviral Transduced Autologous Dendritic Cells Engineered to Express hIL-12(INXN-3001) in Response to an Oral Activator Ligand in Patients With Unresectable Stage III C or IV Malignant Melanoma


Phase 1
18 Years
75 Years
Open (Enrolling)
Both
Melanoma

Thank you

Trial Information

Phase 1b' Open Label, Single Arm, Multicenter Trial to Evaluate the Safety, Tolerance, Response Rate and Immunological Effects of Repeated Intratumoral Injections of Adenoviral Transduced Autologous Dendritic Cells Engineered to Express hIL-12(INXN-3001) in Response to an Oral Activator Ligand in Patients With Unresectable Stage III C or IV Malignant Melanoma


This study will examine the effects of an oral Activator Ligand administration to modulate
the timing of gene expression of human IL-12 by adenovirus-transduced dendritic cells
injected into tumors.


Inclusion Criteria:



1. Males or females of all races ≥ 18 years of age and ≤ 75 years of age;

2. Unresectable Stage III C (in transit) or Stage IV melanoma (M1a, M1b, M1c with LDH ≤
2x ULN), arising from primary cutaneous, mucosal, or subungual melanoma of any tumor
thickness or from an unknown primary site;

3. A minimum of 2-3 accessible nonvisceral lesions (longest diameter ≤3 cm) or palpable
tumor-involved lymph nodes (longest diameter ≤5 cm) for intratumoral injections
(INXN-3001) and biopsies;

4. ECOG performance status of 0 or 1;

5. Patients without visible brain metastases as assessed by contrast-enhanced MRI scan
within 6 weeks prior to receiving study treatment;

6. Adequate baseline hematological and organ function, assessed by laboratory values
within 42 days (6 weeks) prior to study entry and prior to repeat treatment cycles
with INXN-1001 as follows: hemoglobin ≥ 10 g/L, granulocytes > 2500/mm3, lymphocytes
> 1000/ mm3, platelets > 100,000/ mm3, serum creatinine < 1.5 x ULN, AST, ALT,
alkaline phosphatase < 2.5 x ULN, LDH ≤ 2 x ULN, serum bilirubin < 1.5 x ULN,
absolute neutrophils > 500/ mm3;

7. An expected survival of at least approximately 6 months in the opinion of the
investigator (as assessed mainly by performance status);

8. Females must be post-menopausal or surgically sterile or practice effective
contraception; Men who are not surgically sterile and whose partners are not
post-menopausal or surgically sterile must practice effective contraception;

9. Normal coagulation parameters as measured by PT/PTT;

10. Signed, IRB-approved voluntary written informed consent.

Exclusion Criteria:

1. Active, acute viral, bacterial, or fungal infections requiring specific therapy;

2. HIV-infection due to concerns about ability to mount an effective immune response;

3. Active autoimmune disease requiring steroids (>10 mg prednisolone or comparable) or
other immunosuppressive therapy;

4. Patients with detectable brain metastases at the time of screening (or within 6 weeks
prior to receiving study treatment), as assessed by contrast-enhanced MRI scans;

5. Patients with one or more lesion(s) > 3cm (LD) or palpable, tumor-involved lymph
node(s) >5 cm (LD);

6. Patients with a hemoglobin of < 10 g/L;

7. Presence of Stage IV visceral metastases or other distant metastases if LDH >2 x ULN;

8. Patients who have previously been treated with INXN-3001 and INXN-1001;

9. Recipients of organ allografts;

10. Other concurrent, clinically active malignant disease, with the exception of other
cancers of the skin;

11. Less than 30 days (before the first dose of study medication) have elapsed since the
completion of prior chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or
any first line therapy;

12. Clinically significant cerebrovascular disease;

13. History of or concurrent severe cardiac insufficiency (New York Heart Association
Class III or IV) or coronary artery disease;

14. QTc interval of >470 ms on screening;

15. Inability to measure the QT interval due to conduction abnormalities such as Bundle
Branch Block (left or right) or persistent cardiac arrhythmia e.g. atrial
fibrillation, or cardiac pacemaker;

16. Long QT syndrome or family history of sudden cardiac death in young family members;

17. Concomitant use of medication known to affect ventricular repolarization;

18. Cardiac comorbidity such as a left ventricular ejection fraction <45%, myocardial
infarction, persistent angina, or cardiac surgery within 3 months prior to
enrollment;

19. Uncontrollable hypertension (>150 mm Hg systolic or >100 mm Hg diastolic);

20. Acute medical conditions such as ischemic heart or lung disease that may be
considered an unacceptable anesthetic or operative risk;

21. History of or current bleeding or uncorrected clotting disorders;

22. Concurrent immunosuppressive therapy such as corticosteroids (>10mg prednisolone or
comparable) and cyclosporin A;

23. Concurrent investigational treatments, or treatment with any investigational
treatment within the past 30 days (prior to the first dose of study medication);

24. Concurrent medications that are metabolized by the CYP 3A4 pathway;

25. Females who are lactating or pregnant;

26. A Body Mass Index (BMI) greater than or equal to 40 kg/m2; aa. Patients who have a
history of hypersensitivity that may relate to any component of the product, e.g. to
benzoic acid that might be related to INXN-1001, which contains two benzene rings;
bb. Any medical or psychiatric condition which, in the opinion of the investigator,
would unacceptably reduce the safety or delivery of the proposed treatment, or would
preclude obtaining voluntary informed consent.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Physical examinations, vital signs, serum chemistry, urinalysis, hematology, adverse events, and objective response rate, as assessed by diagnostic CT scans

Outcome Time Frame:

throughout the study

Safety Issue:

Yes

Principal Investigator

Andrew Marsh

Investigator Role:

Study Director

Investigator Affiliation:

ZIOPHARM Oncology

Authority:

United States: Food and Drug Administration

Study ID:

RTS-M101B'

NCT ID:

NCT00815607

Start Date:

April 2009

Completion Date:

December 2012

Related Keywords:

  • Melanoma
  • melanoma
  • biologic
  • immunotherapy
  • cancer
  • Melanoma

Name

Location

Helen F. Graham Cancer CenterNewark, Delaware  19713
Oncology Specialists, S.C.Park Ridge, Illinois  60068
Billings ClinicBillings, Montana  59107-7000
The Angeles Clinic and Research InstituteLos Angeles, California  90025
Penn State Milton S. Hershey Medical CenterHershey, Pennsylvania  17033
Mary Crowley Cancer Research CentersDallas, Texas  75201
• Nancy N. and J.C. Lewis Cancer Center & Research Pavilion at St. Joseph/CandlesSavannah, Georgia  31405
Goshen ClinicGoshen, Indiana  46526