Back to results

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

Primary Purpose

Advanced Cancer, Metastatic Cancer, Solid Tumors

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

pbi-shRNA STMN1 LP

About this trial

This is an interventional treatment trial for Advanced Cancer focused on measuring Advanced cancer, Metastatic cancer, solid tumors, Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Surgery involving general anesthesia, chemotherapy, radiotherapy, or immunotherapy within 3 weeks prior to entering the study.
Patient must not have received any other investigational agents within 4 weeks prior to study entry.
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.
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.
Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission for >/= 2 years.
Kaposi's Sarcoma.
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.
Patients who are pregnant or nursing.
Patients with known HIV.
Patients with chronic Hepatitis B and C infection.
Patients with uncontrolled diseases.

Sites / Locations

Mary Crowley Cancer Research Centers

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

pbi-shRNA STMN1 LP

Arm Description

pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection.

Outcomes

Primary Outcome Measures

To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01505153

First Posted

January 4, 2012

Last Updated

February 16, 2018

Sponsor

Gradalis, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01505153

Brief Title

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

Acronym

STMN1-LP

Official Title

Phase I Trial of Intratumoral Bi-functional shRNA Stathmin 1-knockdown Lipoplex in Patients With Advanced and/or Metastatic Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Completed

Study Start Date

February 2012 (Actual)

Primary Completion Date

March 2017 (Actual)

Study Completion Date

April 13, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gradalis, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Cancer, Metastatic Cancer, Solid Tumors

Keywords

Advanced cancer, Metastatic cancer, solid tumors, Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

pbi-shRNA STMN1 LP

Arm Type

Experimental

Arm Description

pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection.

Intervention Type

Biological

Intervention Name(s)

pbi-shRNA STMN1 LP

Intervention Description

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.

Primary Outcome Measure Information:

Title

To determine the safety of intratumoral administration of pbi-shRNA™ STMN1 LP

Description

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.

Time Frame

1 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed advanced and/or metastatic cancer, and, if limited to a single lesion, not considered a candidate for curative surgery or radiation therapy). Biopsy accessible lesion. Per cohort dose/volume, the volume of the lesion to be injected must be 3x volume of the injectate. Subjects that have completed all acceptable therapies with curative potential that are the current standard of care for their respective diseases. Recovered from all toxicities (≤ Grade 1) related to prior therapies except for alopecia. 1 measurable or evaluable lesion; ≥ 1.8 cm diameter for cohort 1 (see Table 10); injection and biopsy accessible. Age ≥18 years. ECOG performance status (PS) 0-2. 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 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. Negative pregnancy test. Exclusion Criteria: Surgery involving general anesthesia, chemotherapy, radiotherapy, or immunotherapy within 3 weeks prior to entering the study. Patient must not have received any other investigational agents within 4 weeks prior to study entry. 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. 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. Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission for >/= 2 years. Kaposi's Sarcoma. 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. Patients who are pregnant or nursing. Patients with known HIV. Patients with chronic Hepatitis B and C infection. Patients with uncontrolled diseases.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Minal Barve, MD

Organizational Affiliation

Mary Crowley Cancer Research Centers

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mary Crowley Cancer Research Centers

City

Dallas

State/Province

Texas

ZIP/Postal Code

75230

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21612405

Citation

Phadke AP, Jay CM, Wang Z, Chen S, Liu S, Haddock C, Kumar P, Pappen BO, Rao DD, Templeton NS, Daniels EQ, Webb C, Monsma D, Scott S, Dylewski D, Frieboes HB, Brunicardi FC, Senzer N, Maples PB, Nemunaitis J, Tong AW. In vivo safety and antitumor efficacy of bifunctional small hairpin RNAs specific for the human Stathmin 1 oncoprotein. DNA Cell Biol. 2011 Sep;30(9):715-26. doi: 10.1089/dna.2011.1240. Epub 2011 May 25.

Results Reference

background

PubMed Identifier

20596090

Citation

Rao DD, Maples PB, Senzer N, Kumar P, Wang Z, Pappen BO, Yu Y, Haddock C, Jay C, Phadke AP, Chen S, Kuhn J, Dylewski D, Scott S, Monsma D, Webb C, Tong A, Shanahan D, Nemunaitis J. Enhanced target gene knockdown by a bifunctional shRNA: a novel approach of RNA interference. Cancer Gene Ther. 2010 Nov;17(11):780-91. doi: 10.1038/cgt.2010.35. Epub 2010 Jul 2.

Results Reference

background

PubMed Identifier

18759697

Citation

Rana S, Maples PB, Senzer N, Nemunaitis J. Stathmin 1: a novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther. 2008 Sep;8(9):1461-70. doi: 10.1586/14737140.8.9.1461.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs