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Phase I Intratumoral Pbi-shRNA STMN1 LP in Advanced and/or Metastatic Cancer (STMN1-LP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01505153
Recruitment Status : Completed
First Posted : January 6, 2012
Last Update Posted : February 22, 2018
Sponsor:
Information provided by (Responsible Party):
Gradalis, Inc.

Tracking Information
First Submitted Date  ICMJE January 4, 2012
First Posted Date  ICMJE January 6, 2012
Last Update Posted Date February 22, 2018
Actual Study Start Date  ICMJE February 2012
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2012)
To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP [ Time Frame: 1 month ]
To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP in patients with superficial advanced and/or metastatic cancer who have no acceptable form of standard therapy.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Intratumoral Pbi-shRNA STMN1 LP in Advanced and/or Metastatic Cancer
Official Title  ICMJE Phase I Trial of Intratumoral Bi-functional shRNA Stathmin 1-knockdown Lipoplex in Patients With Advanced and/or Metastatic Cancer
Brief Summary This is a Phase I safety trial of bifunctional shRNA-STMN1 (pbi-shRNA™STMN1) BIV (bilamellar invaginated vesicle) lipoplex (LP), pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. Patients with superficially accessible advanced cancer following prior therapies will be entered into the study following a modified dose escalation design based on the demonstrated safety of our previous clinical experience (BB-IND 13744) with the same liposome and vector DNA backbone expressing a different transgene (of which doses up to 7 mg DNA IV/single dose have been administered). Patients will accrue in 4-patient escalation cohorts using a modified Fibronacci escalation schema (100%-50%-33%-33%) at a starting intratumoral dose of 0.010 mg/kg of DNA through a dose of 0.053 mg/kg DNA intratumoral / single dose. Should a single, but not more than two (2), ≥ Grade 3 Dose Limiting Toxicity (DLT) occur in any cohort, following mandated review (see below) an additional two (2) patients will be accrued at that dose (total of six). If more than one ≥ Grade 3 toxicity occurs in any cohort, the preceding dose cohort will be expanded to six (from four) and if < 2/6 patients experience ≥ Grade 3 toxicity, that dose will be the Phase II recommended dose. Should no ≥ Grade 3 toxicity occur in any cohort (other than Grade 3 local injection site reaction), an additional two (2) patients will be treated at 0.053 mg/kg DNA intratumoral / single dose.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Cancer
  • Metastatic Cancer
  • Solid Tumors
Intervention  ICMJE Biological: pbi-shRNA STMN1 LP
This is a Phase I safety trial of bifunctional shRNA-STMN1 (pbi-shRNA™STMN1) BIV (bilamellar invaginated vesicle) lipoplex (LP), pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. Patients will accrue in 4-patient escalation cohorts using a modified Fibronacci escalation schema at a starting intratumoral dose of 0.010 mg/kg of DNA through a dose of 0.053 mg/kg DNA intratumoral / single dose.
Study Arms  ICMJE Experimental: pbi-shRNA STMN1 LP
pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection.
Intervention: Biological: pbi-shRNA STMN1 LP
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 24, 2017)
20
Original Estimated Enrollment  ICMJE
 (submitted: January 5, 2012)
22
Actual Study Completion Date  ICMJE April 13, 2017
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed advanced and/or metastatic cancer, and, if limited to a single lesion, not considered a candidate for curative surgery or radiation therapy).
  2. Biopsy accessible lesion.
  3. Per cohort dose/volume, the volume of the lesion to be injected must be 3x volume of the injectate.
  4. Subjects that have completed all acceptable therapies with curative potential that are the current standard of care for their respective diseases.
  5. Recovered from all toxicities (≤ Grade 1) related to prior therapies except for alopecia.
  6. 1 measurable or evaluable lesion; ≥ 1.8 cm diameter for cohort 1 (see Table 10); injection and biopsy accessible.
  7. Age ≥18 years.
  8. ECOG performance status (PS) 0-2.
  9. Organ and marrow function as defined below:

    Absolute granulocyte count ≥ 1,500/mm^3 Platelets ≥ 100,000/mm^3 Total bilirubin ≤ 1.5x institutional ULN Creatinine ≤ 2.0 mg/dL

  10. Ability to understand and the willingness to sign a written informed consent document including permission for pre- and Days 1 and 2 post- injection biopsy and Day 8 injected lesion excision.
  11. Negative pregnancy test.

Exclusion Criteria:

  1. Surgery involving general anesthesia, chemotherapy, radiotherapy, or immunotherapy within 3 weeks prior to entering the study.
  2. Patient must not have received any other investigational agents within 4 weeks prior to study entry.
  3. Patients with known brain metastases unless treated with whole brain radiation and stable for >/= 2 months or treated with stereotactic radiotherapy only and stable for >/=1 month.
  4. Short term (<30 days) concurrent systemic steroids ≤0.125 mg/kg prednisone per day (maximum 7.5 mg/day) and bronchodilators (inhaled steroids) are permitted; other steroid regimens and/or immunosuppressives are excluded.
  5. Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission for >/= 2 years.
  6. Kaposi's Sarcoma.
  7. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  8. Patients who are pregnant or nursing.
  9. Patients with known HIV.
  10. Patients with chronic Hepatitis B and C infection.
  11. Patients with uncontrolled diseases.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01505153
Other Study ID Numbers  ICMJE CL-PTL 103
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gradalis, Inc.
Study Sponsor  ICMJE Gradalis, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Minal Barve, MD Mary Crowley Cancer Research Centers
PRS Account Gradalis, Inc.
Verification Date February 2018

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