LymphomaPhase 1NCT00644072
SNX-5422 to Treat Solid Tumor Cancers and Lymphomas
A Phase 1 study testing SNX-5422 in people with Lymphoma and Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: SNX-5422 is an experimental drug that inhibits a protein called Hsp90, which is important for the growth of tumor cells. SNX-5422 has shown some activity against tumors in the laboratory and animal studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- SNX-5422
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Mar 2008to 16 Jun 2011
- 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
- Patients with histologically documented (by the NIH pathology department) solid tumors and lymphoid malignancies (lymphoma and CLL) who are refractory to standard therapy or who have no acceptable standard treatment options. Patients with lymphoid malignancies will be eligible if their disease has progressed following 2 standard therapies (aggressive NHL), and if their disease is considered refractory (for indolent NHL).
- Patients must have measurable or evaluable disease.
- Patients must have recovered to at least Grade less than or equal to1 toxicity levels due to adverse events and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C, or UCN-01). Patients must be greater than or equal to 2 weeks since any prior administration of study drug in an exploratory IND/Phase Zero study. Patients must be greater than or equal to 1 month since any prior radiation or major surgery. However, patients receiving bisphosphonates for any cancer or undergoing androgen deprivation therapy for prostate cancer are eligible for this therapy.
- Age greater than or equal to 18 years
- The Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
- Life expectancy greater than 3 months
Show all 17Show fewer
- Patients must have normal or adequate organ and marrow function as defined below:
- Absolute neutrophil count greater than or equal to 1,500/milliliter
- Platelets greater than or equal to 100,000/milliliter
- Total bilirubin* within less than or equal to 1.5 times upper limit of normal
- AST (SGOT)/ALT (SGPT) less than or equal to 2.5 times institutional upper limit of normal
- creatinine less than 1.5 times upper limit of normal
- OR
- creatinine clearance greater than or equal to 60 mL/min (measured) for patients with creatinine levels greater than or equal to 1.5 times upper limit of normal.
- we will allow patients with Gilbert's syndrome with total bilirubin up to 2.5 mg/dL
- The effects of SNX-5422 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry, for the duration of study participation, and for 2 months after discontinuation from the study. Women of childbearing potential must have a negative pregnancy test in order to be eligible. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SNX-5422, breastfeeding should be discontinued if the mother is treated with SNX-5422.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients receiving any other investigational agents. Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the principal investigator.
- Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (AHA Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- HIV-positive patients receiving combination antiretroviral therapy are excluded from the study because of possible PK interactions with SNX-5422. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that SNX-5422 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to SNX-5422.
- Chronic diarrhea.
- Gastrointestinal diseases that could affect drug absorption, including postsurgical states such as gastric bypass.
- Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Phase I Study of SNX-5422 Mesylate in Adults With Refractory Solid Tumor Malignancies and Lymphomas
Background:
SNX-5422 is an experimental drug that inhibits a protein called Hsp90, which is important for the growth of tumor cells.
Read more
SNX-5422 has shown some activity against tumors in the laboratory and animal studies.
Objectives:
To determine the highest safe dose, or maximum tolerated dose (MTD), of SNX-5422 that can safely be given to patients with solid tumor cancers and lymphomas when taken twice a week.
To learn how the body's blood and tissue cells react to SNX-5422.
To examine the effects of SNX-5422 on tumors and lymphomas.
Eligibility:
Patients 18 years of age or older who have solid tumor cancers or lymphomas that do not respond to standard therapy or for whom no acceptable standard treatment is available.
Design:
SNX-5422 is taken by mouth twice a week in 28-day cycles. Treatment may continue as long as the cancer does not worsen and side effects are acceptable. Three to six patients are enrolled in the study at a time. Each group is given a higher dose of SNX-5422 than the previous, as long as the preceding dose was tolerated and until the MTD is determined. When the MTD is found, six more patients are enrolled at that dose level.
During the treatment period, patients undergo the following tests and procedures:
- Clinic visits for a physical examination each treatment cycle to check on health status.
- Blood tests for routine laboratory values, to determine how the body handles SNX-5422, and to examine the effects of SNX-5422 on blood cells and other targets.
- Urine tests as needed, depending on the results of blood tests.
- CT scans, or other imaging tests every 8 weeks to evaluate the tumor response to treatment.
- Tumor biopsy (surgical removal of a tissue sample for examination under a microscope) before the first dose of SNX-5422 and again 24 hours after the first dose to see how the drug affects the tumor. This test is optional.
Read the detailed description
Background:
- Inhibitors of the chaperone protein Hsp90 are of current interest because of the central role that Hsp90 plays in the maturation and maintenance of numerous proteins, such as Her2, critical for tumor cell viability and growth.
- Disruption of Hsp90 function has been shown to cause degradation of multiple Hsp90 client proteins, leading to inhibition of several key signaling pathways. This in turn results in inhibition of cellular proliferation.
Objectives:
- Determine the maximum tolerated dose (MTD) of SNX-5422 when administered twice a week for 28 days.
- Characterize the safety profile of SNX-5422 when administered twice a week for 28 days.
- Investigate the effects of SNX-5422 on Hsp90 client proteins using pharmacodynamic (PD) assays.
- Investigate the effects of SNX-5422 on tumor and lymphoma response using the National Cancer Institute (NCI) Response Evaluation Criteria in Solid Tumors (RECIST) criteria) and standardized lymphoma criteria, respectively.
- Determine the pharmacokinetic (PK) profile of SNX-2112 and its prodrug SNX-5422 in humans.
Eligibility:
- Patients with histologically documented solid tumors and lymphoid malignancies (lymphoma and CLL) whose disease has progressed following standard therapy, or who have no acceptable standard treatment options.
- Patients with no major surgery, radiation, or chemotherapy within 4 weeks prior to study enrollment, and who have recovered from toxicities from prior therapies to at least eligibility levels.
Design:
This will be a Phase I dose escalation study to determine the MTD and recommended Phase II dose of SNX-5422. SNX-5422 will be administered orally twice a week for 28 days in continuous cycles until disease progression occurs or the patient meets off-study criteria. Three to six patients will be enrolled at each dose level, and up to 6 additional patients at the MTD, for a minimum of up to 36 patients and a maximum of 60 patients.
- Being tested
- SNX-5422
- Keywords
- Hsp90 Inhibitor, Her2, Neoplasms, Advanced Cancer, Cancer, Solid Tumor, Lymphoma
- Medical subject headings
- Lymphoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SNX-5422Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the maximum tolerated dose (MTD) of SNX-5422 when administered twice a week for 28 days.
Secondary outcomes (1)
Investigate the effects of SNX-5422 on Hsp90 client proteins using pharmacodynamic (PD) assays.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2008 (estimated)
- Study start7 Mar 2008
- Primary completion30 Jun 2009
- Study completion16 Jun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00644072
- Sponsor's protocol ID
- 080091
- Other IDs
- 08-C-0091
- Status last verified
- 16 Jun 2011
- First submitted
- 25 Mar 2008
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Chung EJ, Lee MJ, Lee S, Trepel JB. Assays for pharmacodynamic analysis of histone deacetylase inhibitors. Expert Opin Drug Metab Toxicol. 2006 Apr;2(2):213-30. doi: 10.1517/17425255.2.2.213.
PubMed 16866608Chung EJ, Lee S, Sausville EA, Ryan Q, Karp JE, Gojo I, Telford WG, Lee MJ, Kong HS, Trepel JB. Histone deacetylase inhibitor pharmacodynamic analysis by multiparameter flow cytometry. Ann Clin Lab Sci. 2005 Autumn;35(4):397-406.
PubMed 16254255Posadas EM, Gulley J, Arlen PM, Trout A, Parnes HL, Wright J, Lee MJ, Chung EJ, Trepel JB, Sparreboom A, Chen C, Jones E, Steinberg SM, Daniels A, Figg WD, Dahut WL. A phase II study of perifosine in androgen independent prostate cancer. Cancer Biol Ther. 2005 Oct;4(10):1133-7. doi: 10.4161/cbt.4.10.2064. Epub 2005 Oct 1.
PubMed 16138006
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of SNX-5422 Mesylate in Adults With Refractory Solid Tumor Malignancies and Lymphomas
- ClinicalTrials.gov ID
- NCT00644072
- Acronym / sponsor ID
- 080091
- Keywords
- Hsp90 Inhibitor, Her2, Neoplasms, Advanced Cancer, Cancer, Solid Tumor, Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 7 Mar 2008
- Primary completion
- 30 Jun 2009 (actual)
- Study completion
- 16 Jun 2011 (actual)
- First posted
- 26 Mar 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.
Background:
SNX-5422 is an experimental drug that inhibits a protein called Hsp90, which is important for the growth of tumor cells.
SNX-5422 has shown some activity against tumors in the laboratory and animal studies.
Objectives:
To determine the highest safe dose, or maximum tolerated dose (MTD), of SNX-5422 that can safely be given to patients with solid tumor cancers and lymphomas when taken twice a week.
To learn how the body's blood and tissue cells react to SNX-5422.
To examine the effects of SNX-5422 on tumors and lymphomas.
Eligibility:
Patients 18 years of age or older who have solid tumor cancers or lymphomas that do not respond to standard therapy or for whom no acceptable standard treatment is available.
Design:
SNX-5422 is taken by mouth twice a week in 28-day cycles. Treatment may continue as long as the cancer does not worsen and side effects are acceptable. Three to six patients are enrolled in the study at a time. Each group is given a higher dose of SNX-5422 than the previous, as long as the preceding dose was tolerated and until the MTD is determined. When the MTD is found, six more patients are enrolled at that dose level.
During the treatment period, patients undergo the following tests and procedures:
- Clinic visits for a physical examination each treatment cycle to check on health status.
- Blood tests for routine laboratory values, to determine how the body handles SNX-5422, and to examine the effects of SNX-5422 on blood cells and other targets.
- Urine tests as needed, depending on the results of blood tests.
- CT scans, or other imaging tests every 8 weeks to evaluate the tumor response to treatment.
- Tumor biopsy (surgical removal of a tissue sample for examination under a microscope) before the first dose of SNX-5422 and again 24 hours after the first dose to see how the drug affects the tumor. This test is optional.
Detailed description
Background:
- Inhibitors of the chaperone protein Hsp90 are of current interest because of the central role that Hsp90 plays in the maturation and maintenance of numerous proteins, such as Her2, critical for tumor cell viability and growth.
- Disruption of Hsp90 function has been shown to cause degradation of multiple Hsp90 client proteins, leading to inhibition of several key signaling pathways. This in turn results in inhibition of cellular proliferation.
Objectives:
- Determine the maximum tolerated dose (MTD) of SNX-5422 when administered twice a week for 28 days.
- Characterize the safety profile of SNX-5422 when administered twice a week for 28 days.
- Investigate the effects of SNX-5422 on Hsp90 client proteins using pharmacodynamic (PD) assays.
- Investigate the effects of SNX-5422 on tumor and lymphoma response using the National Cancer Institute (NCI) Response Evaluation Criteria in Solid Tumors (RECIST) criteria) and standardized lymphoma criteria, respectively.
- Determine the pharmacokinetic (PK) profile of SNX-2112 and its prodrug SNX-5422 in humans.
Eligibility:
- Patients with histologically documented solid tumors and lymphoid malignancies (lymphoma and CLL) whose disease has progressed following standard therapy, or who have no acceptable standard treatment options.
- Patients with no major surgery, radiation, or chemotherapy within 4 weeks prior to study enrollment, and who have recovered from toxicities from prior therapies to at least eligibility levels.
Design:
This will be a Phase I dose escalation study to determine the MTD and recommended Phase II dose of SNX-5422. SNX-5422 will be administered orally twice a week for 28 days in continuous cycles until disease progression occurs or the patient meets off-study criteria. Three to six patients will be enrolled at each dose level, and up to 6 additional patients at the MTD, for a minimum of up to 36 patients and a maximum of 60 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients with histologically documented (by the NIH pathology department) solid tumors and lymphoid malignancies (lymphoma and CLL) who are refractory to standard therapy or who have no acceptable standard treatment options. Patients with lymphoid malignancies will be eligible if their disease has progressed following 2 standard therapies (aggressive NHL), and if their disease is considered refractory (for indolent NHL).
- Patients must have measurable or evaluable disease.
- Patients must have recovered to at least Grade less than or equal to1 toxicity levels due to adverse events and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C, or UCN-01). Patients must be greater than or equal to 2 weeks since any prior administration of study drug in an exploratory IND/Phase Zero study. Patients must be greater than or equal to 1 month since any prior radiation or major surgery. However, patients receiving bisphosphonates for any cancer or undergoing androgen deprivation therapy for prostate cancer are eligible for this therapy.
- Age greater than or equal to 18 years
- The Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
Key exclusion criteria (6 listed)
- Patients receiving any other investigational agents. Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the principal investigator.
- Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (AHA Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- HIV-positive patients receiving combination antiretroviral therapy are excluded from the study because of possible PK interactions with SNX-5422. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that SNX-5422 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to SNX-5422.
- Chronic diarrhea.
- Gastrointestinal diseases that could affect drug absorption, including postsurgical states such as gastric bypass.
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 |
|---|---|---|
| SNX-5422 | Drug | – |
Primary outcome
Determine the maximum tolerated dose (MTD) of SNX-5422 when administered twice a week for 28 days.
1 secondary outcome
Investigate the effects of SNX-5422 on Hsp90 client proteins using pharmacodynamic (PD) assays.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 16866608Chung EJ, Lee MJ, Lee S, Trepel JB. Assays for pharmacodynamic analysis of histone deacetylase inhibitors. Expert Opin Drug Metab Toxicol. 2006 Apr;2(2):213-30. doi: 10.1517/17425255.2.2.213.
- Background: PubMed 16254255Chung EJ, Lee S, Sausville EA, Ryan Q, Karp JE, Gojo I, Telford WG, Lee MJ, Kong HS, Trepel JB. Histone deacetylase inhibitor pharmacodynamic analysis by multiparameter flow cytometry. Ann Clin Lab Sci. 2005 Autumn;35(4):397-406.
- Background: PubMed 16138006Posadas EM, Gulley J, Arlen PM, Trout A, Parnes HL, Wright J, Lee MJ, Chung EJ, Trepel JB, Sparreboom A, Chen C, Jones E, Steinberg SM, Daniels A, Figg WD, Dahut WL. A phase II study of perifosine in androgen independent prostate cancer. Cancer Biol Ther. 2005 Oct;4(10):1133-7. doi: 10.4161/cbt.4.10.2064. Epub 2005 Oct 1.
Related trials for Lymphoma
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SNX-5422 in people with Lymphoma and Neoplasms, run by National Cancer Institute (NCI) at 1 site 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 17 inclusion and 6 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: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Determine the maximum tolerated dose (MTD) of SNX-5422 when administered twice a week for 28 days.. 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 NCT00644072, which also lists 3 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 2 Jul 2017.