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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Gradalis, Inc.
Sponsor:
Information provided by (Responsible Party):
Gradalis, Inc.
ClinicalTrials.gov Identifier:
NCT01505153
First received: January 4, 2012
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Advanced Cancer
Metastatic Cancer
Solid Tumors
Biological: pbi-shRNA STMN1 LP
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Intratumoral Bi-functional shRNA Stathmin 1-knockdown Lipoplex in Patients With Advanced and/or Metastatic Cancer

Resource links provided by NLM:


Further study details as provided by Gradalis, Inc.:

Primary Outcome Measures:
  • To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 22
Study Start Date: February 2012
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pbi-shRNA STMN1 LP
pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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 ClinicalTrials.gov identifier: NCT01505153

Locations
United States, Texas
Mary Crowley Cancer Research Centers Recruiting
Dallas, Texas, United States, 75230
Contact: Referral Office    972-566-3000    referral@marycrowley.org   
Principal Investigator: Minal Barve, MD         
Sponsors and Collaborators
Gradalis, Inc.
Investigators
Principal Investigator: Minal Barve, MD Mary Crowley Cancer Research Centers