Safety Study of CALAA-01 to Treat Solid Tumor Cancers

Phase 1

Terminated

• Conditions: Cancer; Solid Tumor
• Interventions: Drug: CALAA-01

• Registration Number: NCT00689065
• Lead Sponsor: Calando Pharmaceuticals

Brief Summary

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.

Detailed Description

CALAA-01 is a targeted nanocomplex that contains anti-R2 siRNA. The complete nanocomplex formulation consists of four components:

1. a duplex of synthetic, non-chemically-modified siRNA (C05C)

2. a cyclodextrin-containing polymer (CAL101),

3. a stabilizing agent (AD-PEG), and

4. 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.

Study Timeline

• Study Start: 2008-05
• Study First Submitted: 2008-05-29
• Study First Submitted QC: 2008-05-29
• Study First Posted: 2008-06-03
• Primary Completion: 2012-09
• Study Completion: 2012-09
• Status Verified: 2013-10
• Last Update Submitted: 2013-10-30
• Last Update Posted: 2013-11-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CALAA-01	CALAA-01	-

Primary Outcome Measures

Name	Time	Method
To determine the tolerability, safety profile and maximum tolerated dose (MTD) of intravenous CALAA-01.	3 months

Secondary Outcome Measures

Name	Time	Method
To characterize the pharmacokinetics (PK) of CALAA-01 after intravenous administration.	3 Months
To determine preliminary efficacy of intravenous CALAA-01 by evaluating tumor response.	3 months
To recommend an intravenous dose of CALAA-01 for future clinical studies.	3 month
To evaluate immune response, by measuring antibody and cytokine levels, and effect of intravenous CALAA-01 on complement.	3 month

Trial Locations

Locations (3)

UCLA Jonsson Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

START (South Texas Accelerated Research Therapeutics); 🇺🇸 San Antonio, Texas, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States