CancerPhase 1NCT00689065
Safety Study of CALAA-01 to Treat Solid Tumor Cancers
A Phase 1 study testing CALAA-01 in people with Cancer and Solid Tumor, run by Calando Pharmaceuticals at 3 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Solid Tumor
- What is being tested?
- CALAA-01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2008to Sep 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- A myocardial infarction within six (6) months prior to enrollment or having New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, cardiomyopathy, severe uncontrolled ventricular arrhythmias, left bundle branch block, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities (e.g., Long QT interval, Torsade de Pointes).
- Poorly controlled hypertension
- Prior corticosteroids as anticancer therapy within seven (7) days of baseline.
- Active CNS metastases or currently receiving dexamethasone for CNS disease.
- Major surgery within four (4) weeks of baseline.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
City of Hope National Medical Center
Duarte, California, 91010
UCLA Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
START (South Texas Accelerated Research Therapeutics)
San Antonio, Texas, 78229
About this study
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
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.
Read the detailed description
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.
- Conditions
- Cancer, Solid Tumor
- Being tested
- CALAA-01
- Keywords
- siRNA, RNA interference (RNAi), Cyclodextrin, Cancer, Neoplasms, Solid Tumor, Ovarian Cancer, Lung Cancer, Non Small Cell Lung Cancer, Pancreatic Cancer, Breast Cancer, Colon Cancer, Endometrial Cancer, Kidney (Renal Cell) Cancer, Melanoma, Prostate Cancer, Skin Cancer, Thyroid Cancer, Solid Malignancies
- Medical subject headings
- Neoplasms, Ovarian Neoplasms, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Pancreatic Neoplasms, Breast Neoplasms, Colonic Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CALAA-01Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| CALAA-01 | Experimental | Not described Receives: Drug: CALAA-01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the tolerability, safety profile and maximum tolerated dose (MTD) of intravenous CALAA-01.
Measured: 3 months
Secondary outcomes (4)
To characterize the pharmacokinetics (PK) of CALAA-01 after intravenous administration.
Measured: 3 Months
To determine preliminary efficacy of intravenous CALAA-01 by evaluating tumor response.
Measured: 3 months
To recommend an intravenous dose of CALAA-01 for future clinical studies.
Measured: 3 month
To evaluate immune response, by measuring antibody and cytokine levels, and effect of intravenous CALAA-01 on complement.
Measured: 3 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2008 (estimated)
- Study startMay 2008
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Calando Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Antoni Ribas, M.D., Principal investigator, UCLA Jonsson Comprehensive Cancer CenterAnthony W Tolcher, M.D., Principal investigator, START (South Texas Accelerated Research Therapeutics)Yun Yen, M.D., Ph.D., Principal investigator, City of Hope National Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00689065
- Sponsor's protocol ID
- CALAA-01-ST-001
- Status last verified
- Oct 2013
- First submitted
- 29 May 2008
- Last updated
- 1 Nov 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 17379663Heidel 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.
PubMed 17404105Bartlett 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.
PubMed 17929316Heidel 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.
PubMed 16948559Davis 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.
PubMed 20305636
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00689065
- Acronym / sponsor ID
- CALAA-01-ST-001
- Conditions
- Cancer, Solid Tumor
- Keywords
- siRNA, RNA interference (RNAi), Cyclodextrin, Cancer, Neoplasms, Solid Tumor, Ovarian Cancer, Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Calando PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2008
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 3 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CALAA-01 | Experimental | Drug: CALAA-01 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subjects must be at least eighteen (18) years of age.
- Subjects must have the following:
- 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).
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CALAA-01Subjects 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. | Drug | CALAA-01 |
Primary outcome
To determine the tolerability, safety profile and maximum tolerated dose (MTD) of intravenous CALAA-01.
Time frame: 3 months
4 secondary outcomes
To characterize the pharmacokinetics (PK) of CALAA-01 after intravenous administration.
Time frame: 3 Months
To determine preliminary efficacy of intravenous CALAA-01 by evaluating tumor response.
Time frame: 3 months
To recommend an intravenous dose of CALAA-01 for future clinical studies.
Time frame: 3 month
To evaluate immune response, by measuring antibody and cytokine levels, and effect of intravenous CALAA-01 on complement.
Time frame: 3 month
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2013.
- Background: PubMed 17379663Heidel 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.
- Background: PubMed 17404105Heidel 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.
- Background: PubMed 17929316Bartlett 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.
- Background: PubMed 16948559Heidel 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.
- Results publication: PubMed 20305636Davis 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.
- Calando Pharmaceuticals WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antoni Ribas, M.D. principal investigator
UCLA Jonsson Comprehensive Cancer Center
Anthony W Tolcher, M.D. principal investigator
START (South Texas Accelerated Research Therapeutics)
Yun Yen, M.D., Ph.D. principal investigator
City of Hope National Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CALAA-01 in people with Cancer and Solid Tumor, run by Calando Pharmaceuticals at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the tolerability, safety profile and maximum tolerated dose (MTD) of intravenous CALAA-01. (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00689065, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2013.