Safety Study of CALAA-01 to Treat Solid Tumor Cancers
A Phase I, Dose-Escalating Study of the Safety of Intravenous CALAA-01 in Adults With Solid Tumors Refractory to Standard-of-Care Therapies
1 other identifier
interventional
24
1 country
3
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 cancer
Started May 2008
Typical duration for phase_1 cancer
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2008
CompletedFirst Submitted
Initial submission to the registry
May 29, 2008
CompletedFirst Posted
Study publicly available on registry
June 3, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2012
CompletedNovember 1, 2013
October 1, 2013
4.3 years
May 29, 2008
October 30, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To determine the tolerability, safety profile and maximum tolerated dose (MTD) of intravenous CALAA-01.
3 months
Secondary Outcomes (4)
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
Study Arms (1)
CALAA-01
EXPERIMENTALInterventions
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.
Eligibility Criteria
You may qualify if:
- Subjects must be at least eighteen (18) years of age.
- Subjects must have the following:
- Histologically- or cytologically-confirmed solid malignancy that is measurable or non-measurable recurrent or metastatic disease (i.e., evaluable; e.g., cytologically or radiologically-detectable disease, markers, etc.)
- Measurable disease is metastatic or unresectable
- Standard curative or palliative measures do not exist, are no longer effective, or are unlikely to be effective.
- Subjects must have tumors that have recurred after previous surgery and/or radiation.
- Subjects must have received prior adjuvant, neoadjuvant, or any other therapy for metastatic disease. No restriction is placed on the number of cycles or regimens of prior therapy.
- Subjects must have fully recovered from diagnostic or therapeutic surgery (i.e., complete wound healing).
- Subjects must have fully recovered from prior radiotherapy for local symptom palliation.
- Subjects must have recovered from the toxic effects of prior therapy.
- Women and men of child-bearing/conceiving potential must be willing to use highly effective contraceptive methods during the course of the study. Any female who is not sexually active must agree to begin using highly effective contraceptive methods if she becomes sexually active during the study. Females who are post-menopausal (i.e., no longer menstruating) must have been so for two (2) years.
- Females of child-bearing potential (e.g., not surgically sterilized or two (2) years post-menopausal) must have a negative urine pregnancy test at screening. Positive tests will be confirmed serologically.
- Subjects must have adequate marrow, hepatic, and renal function at the time of screening,.
- Subjects must be willing and able, in the opinion of the Investigator, to comply with the protocol tests and procedures.
- Subjects must be willing and able to give written informed consent.
You may not qualify if:
- Pregnant or nursing females.
- Clinically-evident (e.g., abdominal distention, bulging and/or fluid wave) ascites or Grade 3 peripheral edema.
- Allergy(ies) to contrast media required for protocol testing.
- History of significant weight loss within four (4) weeks prior to baseline.
- Evidence of active, uncontrolled infection or unstable or severe intercurrent medical conditions.
- Peripheral venous access insufficient to permit infusion of intravenous CALAA-01 and acquisition of laboratory specimens.
- Alcoholism (dependency), alcohol or substance abuse within twelve (12) months prior to screening that has caused health consequences.
- Immunocompromised subjects, subjects with known autoimmune conditions, active hepatitis or human immunodeficiency virus (HIV) seropositivity.
- Prior gene transfer therapy or prior therapy with a cytolytic virus of any type.
- Any electrocardiogram (ECG) abnormality at screening documented by the Principal Investigator as clinically significant.
- Vaccinations of any kind within thirty (30) days of baseline.
- Use of any investigational agent or device within thirty (30) days of CALAA-01 administration.
- Any concomitant medical or psychiatric condition or social situation that would make it difficult to comply with protocol requirements.
- Subjects requiring anticonvulsants.
- Radiotherapy, cytotoxic chemotherapy, biologic, hormonal or immunotherapy or bone marrow transplantation within four (4) weeks of baseline; nitroureas within six (6) weeks. Current use of growth factors.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
City of Hope National Medical Center
Duarte, California, 91010, United States
UCLA Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
START (South Texas Accelerated Research Therapeutics)
San Antonio, Texas, 78229, United States
Related Publications (5)
Heidel JD, Yu Z, Liu JY, Rele SM, Liang Y, Zeidan RK, Kornbrust DJ, Davis ME. Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5715-21. doi: 10.1073/pnas.0701458104. Epub 2007 Mar 22.
PMID: 17379663BACKGROUNDHeidel JD, Liu JY, Yen Y, Zhou B, Heale BS, Rossi JJ, Bartlett DW, Davis ME. Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo. Clin Cancer Res. 2007 Apr 1;13(7):2207-15. doi: 10.1158/1078-0432.CCR-06-2218.
PMID: 17404105BACKGROUNDBartlett DW, Davis ME. Impact of tumor-specific targeting and dosing schedule on tumor growth inhibition after intravenous administration of siRNA-containing nanoparticles. Biotechnol Bioeng. 2008 Mar 1;99(4):975-85. doi: 10.1002/bit.21668.
PMID: 17929316BACKGROUNDHeidel JD. Linear cyclodextrin-containing polymers and their use as delivery agents. Expert Opin Drug Deliv. 2006 Sep;3(5):641-6. doi: 10.1517/17425247.3.5.641.
PMID: 16948559BACKGROUNDDavis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, Yen Y, Heidel JD, Ribas A. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature. 2010 Apr 15;464(7291):1067-70. doi: 10.1038/nature08956. Epub 2010 Mar 21.
PMID: 20305636RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- 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
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 29, 2008
First Posted
June 3, 2008
Study Start
May 1, 2008
Primary Completion
September 1, 2012
Study Completion
September 1, 2012
Last Updated
November 1, 2013
Record last verified: 2013-10