Solid TumorsPhase 1NCT01246102
AT13387 in Adults With Refractory Solid Tumors
A Phase 1 study testing AT13387 in people with Solid Tumors and Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: The experimental drug AT13387 has been shown to have some anticancer effects against tumor cells by blocking a protein that affects other proteins inside certain cancer cells, and helps to prevent the cancer cells from reproducing and spreading. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Solid Tumors, Breast Cancer
- What is being tested?
- AT13387
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Nov 2010to 27 Oct 2017
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically documented (confirmed at the Laboratory of Pathology, NCI) solid tumor malignancy that is metastatic or unresectable, for which standard curative measures do not exist, or have failed at least one line of standard therapy.
- Patients must have measurable or evaluable disease.
- Patients must have completed any chemotherapy, radiation therapy, or biologic therapy greater than or equal to 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C).
- Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in an exploratory IND/Phase 0 study. Patients must have recovered to eligibility levels from prior toxicity or adverse events. Patients receiving bisphosphonates for any cancer are eligible to participate.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of AT13387 in patients < 18 years of age, children are excluded from this study.
- The Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
Show all 23Show fewer
- Life expectancy > 3 months.
- Patients must have normal or adequate organ and marrow function as defined below:
- Absolute neutrophil count greater than or equal to 1,500/microL
- Platelets greater than or equal to 100,000/microL
- Total bilirubin less than or equal to 1.5 times institutional ULN
- AST (SGOT)/ALT (SGPT) less than or equal to 2.5 times institutional ULN
- Creatinine <1.5 times ULN; OR
- Measured creatinine greater than or equal to 60 mL/minute for patients with clearance creatinine levels greater than or equal to 1.5 times ULN
- The effects of AT13387 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 completion of study. Women of childbearing potential must have a negative pregnancy test within 72 hours of enrollment 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 to nursing infants secondary to treatment of the mother with AT13387, breastfeeding should be discontinued if the mother is treated with AT13387.
- During the expansion phase of the protocol, patients must have:
- Disease amenable to biopsy
- Willingness to undergo pre- and post-treatment biopsies
- Ability to understand and the willingness to sign a written informed consent document.
- Currently enrolling in the expansion phase. Patients must have:
- Disease amenable to biopsy
- Willingness to undergo pre- and post-treatment biopsies
- Both men and women, and members of all races and ethnic groups, are eligible for this trial.
Who cannot join
- Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for greater than or equal to 2 months after treatment of the brain metastases, without steroids or anti-seizure medications. These patients may be enrolled at the discretion of the principal investigator.
- Patients with clinically significant intercurrent illnesses, including but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- QTc > 450 msec for men and > 470 msec for women.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with AT13387.
- Pregnant women are ineligible because the effects of AT13387 on the developing human fetus are unknown.
- Exclude patients with active gastrointestinal bleeding or an event of gastrointestinal bleeding within a week of starting treatment.
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 the HSP-90 Inhibitor, AT13387, in Adults With Refractory Solid Tumors
Background:
- The experimental drug AT13387 has been shown to have some anticancer effects against tumor cells by blocking a protein that affects other proteins inside certain cancer cells, and helps to prevent the cancer cells from reproducing and spreading. AT13387 has not been tested in humans, and researchers are interested in investigating whether it can be used to treat solid tumors that have not responded to standard treatments.
Read more
Objectives:
- To investigate the safety and effectiveness of AT13387 in individuals with solid tumors.
Eligibility:
- Individuals at least 18 years of age who have solid tumors that have not responded to standard treatments.
Design:
- Participants will be screened with a physical examination and medical history, as well as blood tests and tumor imaging studies.
- AT13387 will be given in 28-day cycles of treatment. Participants will receive AT13387 twice a week (2 days in a row) for the first 3 weeks of the cycle, followed by a fourth week without the drug.
- Participants will have regular blood and urine samples, imaging studies, eye examinations, and tumor biopsies to monitor the effects of the treatment.
- Participants will continue treatment with AT13387 unless serious side effects develop or the tumor stops responding to treatment.
Read the detailed description
Background:
- AT13387 is a synthetic Hsp90 inhibitor that has demonstrated improved characteristics over other Hsp90 inhibitors. AT13387 has a long tumor retention half-life and prolonged inhibitory effect on its known oncogenic client proteins.
- AT13387 has demonstrated activity against multiple cancer cell lines and tumor xenografts in pre-clinical models.
Primary Objectives:
- Define the safety and tolerability of AT13387 administered on a QDx2 every week, 3 weeks out of 4 scheduled, in adults with refractory solid tumors.
- Establish the maximum tolerated dose (MTD) of AT13387 administered on a QDx2 every week, 3 weeks out of 4 schedule, in adults with refractory solid tumors.
Secondary Objectives:
- Determine the pharmacokinetics (PK) of AT13387 administered on a QDx2 every week, 3 weeks out of 4 schedule, in adults with refractory solid tumors.
- Assess pharmacodynamic (PD) markers of Hsp90 inhibition and modulation of Hsp90 client proteins by AT13387 in tumor tissue, serum, and PBMCs.
Eligibility:
-Study participants must have histologically confirmed solid tumor malignancy that has progressed or recurred after at least one line of chemotherapy, or for which no standard treatment option exists. Participants enrolling in the expansion phase must have disease amenable to biopsy with willingness to undergo pre- and post-treatment biopsies (Remove the HER 2 archival tissue).
Study Design:
- This study will follow an accelerated titration design 2B with initial dose levels increased in 100% increments.
- The accelerated phase ends when one patient experiences a dose-limiting toxicity or two patients experience Grade 2 drug-related toxicity during the first cycle; when dose level 3 is reached; or at first instance of Grade 2 ocular toxicity in any cycle.
- AT13387 will be administered intravenously, over 1 hour, on 2 consecutive days, 3 out of 4 weeks, every 28 days (i.e., on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle).
- PK and PD studies will be conducted in cycle 1 only. Once the MTD is established, 10 additional patients, will be entered at the MTD to further define toxicity and perform PD studies at this dose; pre- and post-treatment tumor biopsies will be mandatory for these patients.
- CT scans will be performed at baseline and every 2 cycles for restaging.
- Up to 37 patients may be treated.
- Study participants will be offered optional participation in an ongoing NCI imaging study at baseline with a repeat scan following the last dose of AT13387 in cycle 1.
- Conditions
- Solid Tumors, Breast Cancer
- Being tested
- AT13387
- Keywords
- Targeted Therapy, HER2 Positive Cancer, Cancer, Solid Tumor, Breast Cancer
- Medical subject headings
- Breast Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT13387Drug
Treatment will be administered as a 1-hour IV infusion on 2 consecutive days of every week for 3 weeks, followed by a 1-week period without drug administration.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | starting at 20 mg/m2 Receives: Drug: AT13387 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Define the safety and tolerability of AT13387; establishing the MTD of At13387
Measured: 3 weeks
Secondary outcomes (1)
Determine the pharmacokinetics (PK) of AT13387; Assess pharmacodynamic (PD) markers of Hsp90 inhibition and modulation of Hsp90 client proteins by AT13387
Measured: After 1 cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2010 (estimated)
- Study start19 Nov 2010
- Primary completion30 Dec 2013
- Study completion27 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies 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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alice P Chen, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01246102
- Sponsor's protocol ID
- 110029
- Other IDs
- 11-C-0029
- Status last verified
- 27 Oct 2017
- First submitted
- 20 Nov 2010
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL, Kluger HM. High HSP90 expression is associated with decreased survival in breast cancer. Cancer Res. 2007 Apr 1;67(7):2932-7. doi: 10.1158/0008-5472.CAN-06-4511.
PubMed 17409397Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8324-8. doi: 10.1073/pnas.91.18.8324.
PubMed 8078881Bagatell R, Whitesell L. Altered Hsp90 function in cancer: a unique therapeutic opportunity. Mol Cancer Ther. 2004 Aug;3(8):1021-30.
PubMed 15299085Do K, Speranza G, Chang LC, Polley EC, Bishop R, Zhu W, Trepel JB, Lee S, Lee MJ, Kinders RJ, Phillips L, Collins J, Lyons J, Jeong W, Antony R, Chen AP, Neckers L, Doroshow JH, Kummar S. Phase I study of the heat shock protein 90 (Hsp90) inhibitor onalespib (AT13387) administered on a daily for 2 consecutive days per week dosing schedule in patients with advanced solid tumors. Invest New Drugs. 2015 Aug;33(4):921-30. doi: 10.1007/s10637-015-0255-1. Epub 2015 Jun 18.
PubMed 26082332
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of the HSP-90 Inhibitor, AT13387, in Adults With Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT01246102
- Acronym / sponsor ID
- 110029
- Conditions
- Solid Tumors, Breast Cancer
- Keywords
- Targeted Therapy, HER2 Positive Cancer, Cancer, Solid Tumor, Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 19 Nov 2010
- Primary completion
- 30 Dec 2013 (actual)
- Study completion
- 27 Oct 2017 (actual)
- First posted
- 23 Nov 2010 (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:
- The experimental drug AT13387 has been shown to have some anticancer effects against tumor cells by blocking a protein that affects other proteins inside certain cancer cells, and helps to prevent the cancer cells from reproducing and spreading. AT13387 has not been tested in humans, and researchers are interested in investigating whether it can be used to treat solid tumors that have not responded to standard treatments.
Objectives:
- To investigate the safety and effectiveness of AT13387 in individuals with solid tumors.
Eligibility:
- Individuals at least 18 years of age who have solid tumors that have not responded to standard treatments.
Design:
- Participants will be screened with a physical examination and medical history, as well as blood tests and tumor imaging studies.
- AT13387 will be given in 28-day cycles of treatment. Participants will receive AT13387 twice a week (2 days in a row) for the first 3 weeks of the cycle, followed by a fourth week without the drug.
- Participants will have regular blood and urine samples, imaging studies, eye examinations, and tumor biopsies to monitor the effects of the treatment.
- Participants will continue treatment with AT13387 unless serious side effects develop or the tumor stops responding to treatment.
Detailed description
Background:
- AT13387 is a synthetic Hsp90 inhibitor that has demonstrated improved characteristics over other Hsp90 inhibitors. AT13387 has a long tumor retention half-life and prolonged inhibitory effect on its known oncogenic client proteins.
- AT13387 has demonstrated activity against multiple cancer cell lines and tumor xenografts in pre-clinical models.
Primary Objectives:
- Define the safety and tolerability of AT13387 administered on a QDx2 every week, 3 weeks out of 4 scheduled, in adults with refractory solid tumors.
- Establish the maximum tolerated dose (MTD) of AT13387 administered on a QDx2 every week, 3 weeks out of 4 schedule, in adults with refractory solid tumors.
Secondary Objectives:
- Determine the pharmacokinetics (PK) of AT13387 administered on a QDx2 every week, 3 weeks out of 4 schedule, in adults with refractory solid tumors.
- Assess pharmacodynamic (PD) markers of Hsp90 inhibition and modulation of Hsp90 client proteins by AT13387 in tumor tissue, serum, and PBMCs.
Eligibility:
-Study participants must have histologically confirmed solid tumor malignancy that has progressed or recurred after at least one line of chemotherapy, or for which no standard treatment option exists. Participants enrolling in the expansion phase must have disease amenable to biopsy with willingness to undergo pre- and post-treatment biopsies (Remove the HER 2 archival tissue).
Study Design:
- This study will follow an accelerated titration design 2B with initial dose levels increased in 100% increments.
- The accelerated phase ends when one patient experiences a dose-limiting toxicity or two patients experience Grade 2 drug-related toxicity during the first cycle; when dose level 3 is reached; or at first instance of Grade 2 ocular toxicity in any cycle.
- AT13387 will be administered intravenously, over 1 hour, on 2 consecutive days, 3 out of 4 weeks, every 28 days (i.e., on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle).
- PK and PD studies will be conducted in cycle 1 only. Once the MTD is established, 10 additional patients, will be entered at the MTD to further define toxicity and perform PD studies at this dose; pre- and post-treatment tumor biopsies will be mandatory for these patients.
- CT scans will be performed at baseline and every 2 cycles for restaging.
- Up to 37 patients may be treated.
- Study participants will be offered optional participation in an ongoing NCI imaging study at baseline with a repeat scan following the last dose of AT13387 in cycle 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: AT13387starting at 20 mg/m2 |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Patients must have histologically documented (confirmed at the Laboratory of Pathology, NCI) solid tumor malignancy that is metastatic or unresectable, for which standard curative measures do not exist, or have failed at least one line of standard therapy.
- Patients must have measurable or evaluable disease.
- Patients must have completed any chemotherapy, radiation therapy, or biologic therapy greater than or equal to 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C).
- Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in an exploratory IND/Phase 0 study. Patients must have recovered to eligibility levels from prior toxicity or adverse events. Patients receiving bisphosphonates for any cancer are eligible to participate.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of AT13387 in patients < 18 years of age, children are excluded from this study.
Key exclusion criteria (6 listed)
- Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for greater than or equal to 2 months after treatment of the brain metastases, without steroids or anti-seizure medications. These patients may be enrolled at the discretion of the principal investigator.
- Patients with clinically significant intercurrent illnesses, including but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- QTc > 450 msec for men and > 470 msec for women.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with AT13387.
- Pregnant women are ineligible because the effects of AT13387 on the developing human fetus are unknown.
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 |
|---|---|---|
| AT13387Treatment will be administered as a 1-hour IV infusion on 2 consecutive days of every week for 3 weeks, followed by a 1-week period without drug administration. | Drug | 1 |
Primary outcome
Define the safety and tolerability of AT13387; establishing the MTD of At13387
Time frame: 3 weeks
1 secondary outcome
Determine the pharmacokinetics (PK) of AT13387; Assess pharmacodynamic (PD) markers of Hsp90 inhibition and modulation of Hsp90 client proteins by AT13387
Time frame: After 1 cycle
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 5 Jul 2018.
- Background: PubMed 17409397Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL, Kluger HM. High HSP90 expression is associated with decreased survival in breast cancer. Cancer Res. 2007 Apr 1;67(7):2932-7. doi: 10.1158/0008-5472.CAN-06-4511.
- Background: PubMed 8078881Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8324-8. doi: 10.1073/pnas.91.18.8324.
- Background: PubMed 15299085Bagatell R, Whitesell L. Altered Hsp90 function in cancer: a unique therapeutic opportunity. Mol Cancer Ther. 2004 Aug;3(8):1021-30.
- Derived from this study: PubMed 26082332Do K, Speranza G, Chang LC, Polley EC, Bishop R, Zhu W, Trepel JB, Lee S, Lee MJ, Kinders RJ, Phillips L, Collins J, Lyons J, Jeong W, Antony R, Chen AP, Neckers L, Doroshow JH, Kummar S. Phase I study of the heat shock protein 90 (Hsp90) inhibitor onalespib (AT13387) administered on a daily for 2 consecutive days per week dosing schedule in patients with advanced solid tumors. Invest New Drugs. 2015 Aug;33(4):921-30. doi: 10.1007/s10637-015-0255-1. Epub 2015 Jun 18.
Related trials for Solid Tumors
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 1
A Study of MGC030 in Participants With Advanced Solid Tumors
Urothelial Cancer, GastroEsophageal Cancer
RecruitingPhase 1
SW-682 in Advanced Solid Tumors
Advanced Solid Tumor, Mesothelioma, Malignant
RecruitingPhase 1
Study to Evaluate CD8 PET Imaging as a Marker of Immune Response to Stereotactic Body Radiation Therapy (ELIXR)
Metastatic Malignant Solid Neoplasm, Lymphoma
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.
Alice P Chen, M.D. principal investigator
National Cancer Institute (NCI)
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 AT13387 in people with Solid Tumors and Breast Cancer, 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 23 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 5 Jul 2018. 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?
Define the safety and tolerability of AT13387; establishing the MTD of At13387 (time frame: 3 weeks). 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 NCT01246102, which also lists 4 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 5 Jul 2018.