Safety Study of CALAA-01 to Treat Solid Tumor Cancers
Rationale: CALAA-01 is a targeted therapeutic designed to inhibit tumor growth and/or reduce tumor size. The active ingredient in CALAA-01 is a small interfering RNA (siRNA). This siRNA inhibits tumor growth via RNA interference to reduce expression of the M2 subunit of ribonucleotide reductase (R2). The CALAA-01 siRNA is protected from nuclease degradation within a stabilized nanoparticle targeted to tumor cells.
PURPOSE: This phase I trial will:
- Determine the safety, toxicity, and the maximum tolerated dose (MTD) of CALAA-01 when administered intravenously to patients with relapsed or refractory cancer.
- Characterize the pharmacokinetics (PK) of CALAA-01 after intravenous administration.
- Provide preliminary evidence of efficacy of intravenous CALAA-01 by evaluating tumor response.
- Recommend a dose of intravenous CALAA-01 for future clinical studies.
- Evaluate immune response, by measuring antibody and cytokine levels, and the effect of intravenous CALAA-01 on complement.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Dose-Escalating Study of the Safety of Intravenous CALAA-01 in Adults With Solid Tumors Refractory to Standard-of-Care Therapies|
- To determine the tolerability, safety profile and maximum tolerated dose (MTD) of intravenous CALAA-01. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- To characterize the pharmacokinetics (PK) of CALAA-01 after intravenous administration. [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
- To determine preliminary efficacy of intravenous CALAA-01 by evaluating tumor response. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- To recommend an intravenous dose of CALAA-01 for future clinical studies. [ Time Frame: 3 month ] [ Designated as safety issue: No ]
- To evaluate immune response, by measuring antibody and cytokine levels, and effect of intravenous CALAA-01 on complement. [ Time Frame: 3 month ] [ Designated as safety issue: No ]
|Study Start Date:||May 2008|
|Estimated Study Completion Date:||December 2012|
|Estimated Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Subjects with solid tumors who satisfy the eligibility criteria will receive two, 21-day cycles of CALAA-01. A cycle will consist of four (4) 30-minute intravenous infusions administered on days 1, 3, 8, and 10 followed by 11 days of rest. If safe, a second 21-day cycle will be administered consisting of infusions on days 22, 24, 29 and 31 followed by 11 days of rest.
CALAA-01 is a targeted nanocomplex that contains anti-R2 siRNA. The complete nanocomplex formulation consists of four components:
- a duplex of synthetic, non-chemically-modified siRNA (C05C)
- a cyclodextrin-containing polymer (CAL101),
- a stabilizing agent (AD-PEG), and
- a targeting agent (AD-PEG-Tf) that contains the human transferrin protein (Tf). The cationic polymer interacts electrostatically with anionic siRNA to assemble into nanocomplexes below approximately 100 nm in diameter that protect the siRNA from nuclease degradation in serum. The siRNA-containing nanocomplexes are targeted to cells that over express the transferrin receptor (TfR). Upon reaching a target cell, transferrin binds to TfRs on the cell surface and the siRNA-containing nanocomplex enters the cell by endocytosis. Inside the cell, chemistry built into the polymer achieves unpackaging of the siRNA from the nanocomplex, permitting it to function via RNA interference.
|United States, California|
|City of Hope National Medical Center|
|Duarte, California, United States, 91010|
|UCLA Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|United States, Texas|
|START (South Texas Accelerated Research Therapeutics)|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||Antoni Ribas, M.D.||UCLA Jonsson Comprehensive Cancer Center|
|Principal Investigator:||Anthony W Tolcher, M.D.||START (South Texas Accelerated Research Therapeutics)|
|Principal Investigator:||Yun Yen, M.D., Ph.D.||City of Hope National Medical Center|