Metastatic Solid TumorPhase 1NCT01393509
The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies
A Phase 1 study testing PU-H71 in people with Metastatic Solid Tumor and Lymphoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
NOTE: This study is now recruiting only patients with Myeloproliferative Neoplasms (MPN). Dose escalation has been completed. The purpose of this study is to test a new drug, called PU-H71 for the first time in humans, to find out what effects, good or bad, this new drug has on the patient and the cancer at different… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Solid Tumor, Lymphoma, Myeloproliferative Neoplasms (MPN)
- What is being tested?
- PU-H71
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jul 2011to 23 Mar 2023
- 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
- The safety-expansion phase will be open to accrual only for patients with MPN.
- ≥ 18 years of age
- For patients with solid malignancies and lymphoma, radiographically detectable (Either FDG-PET, CT scan/ MRI or Bone Scan) or measurable disease will be required. Measurable disease is defined as at least one measurable lesion ≥ 10 mm on CT scan (15 mm for nodal lesions).
- Prior therapy for advanced malignancy with no current curative option
- Neutrophil count ≥ 1,000/μL, platelet count ≥ 50,000/μL, and hemoglobin ≥ 8 g/dL (Platelet count must be assessed at least 7 days after a prior transfusion, if any)
- Serum bilirubin ≤ 1.5 mg/dL;
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- AST and ALT≤ 1.5 × ULN
- Serum creatinine ≤ 1.5 mg/dL or creatinine clearance of ≥ 50 mL/min based on a 24-hour urine collection
- Patients receiving hydroxyurea may continue receiving it for up to 14 days after the start of protocol treatment if WBC >30 x10^9/L.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Patients with HIV/AIDS are allowed on study if they have an undetectable viral load, CD4 > 300 and on stable Highly Active Antiretroviral Therapy (HAART) regimen for 1 month.
- Patients who have been treated for at least two weeks with stable doses of corticosteroids to address conditions unrelated to their malignancy will be allowed to continue this treatment during enrollment on the current trial.
- Patients currently being treated with a gonadotropin-releasing hormone agonist (GnRH agonist), bicalutamide or with bisphosphonates may continue treatment while on clinical trial PU-H71 as long as the treatment has been initiated before the study start. GnRH agonist must have been well tolerated for at least three months.
- Optional participation in the microdose imaging trial, IRB#10-139.
- Signed written informed consent and HIPAA consent.
- PATIENTS WITH MPN must be:
- On ruxolitinib for at least three months and on a stable dose for at least 1 month prior to enrollment and taking at least 5 mg twice daily of ruxolitinib
- Tolerating ruxolitinib but with persistent manifestations of disease (i.e. persistent splenomegaly, abnormal blood counts, persistent constitutional symptoms residual fibrosis in bone marrow (2+ or greater), or measurable allele burden as evidenced of clonal JAK2 or MPL mutation).
- Ruxilitinib treatment requirements will be waived for patients who have failed this treatment in the past or for whom this treatment is otherwise contraindicated
Who cannot join
- Ejection fraction < 50%, as determined by echocardiogram or MUGA scan
- Symptomatic brain or CNS metastases. Previously treated and stable CNS disease is allowed.
- Any of the following for the treatment of cancer within 2 weeks of first study treatment: chemotherapy, immunotherapy, experimental therapy or biologic therapy.
- Any major surgical procedure or radiation within 4 weeks of first study treatment
- Active liver disease, including viral or other hepatitis, or cirrhosis
- Pregnancy or lactation
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- Active hepatitis or other active infections
- Any other significant medical condition not under control, including any acute coronary syndrome within the past 6 months.
- Patients with a permanent pacemaker
- Patients with a QTcF or QTcB > 480 ms in the baseline EKG
- Systemic corticosteroids (e.g. prednisone ≥ 12.5 mg/day or dexamethasone ≥ 2 mg/day) for the purpose of palliating tumor-related symptoms will not be allowed within 1 week of starting treatment on trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
NOTE: This study is now recruiting only patients with Myeloproliferative Neoplasms (MPN). Dose escalation has been completed.
The purpose of this study is to test a new drug, called PU-H71 for the first time in humans, to find out what effects, good or bad, this new drug has on the patient and the cancer at different dose levels. PU-H71 blocks a protein called Heat Shock Protein-90 (Hsp90). Hsp90 is found in both normal and cancer cells, but may be more important in cancer cells. Attacking Hsp90 can stop the function of certain proteins that are needed for cancer cells to survive. The diseases that are part of this study may be especially sensitive to attacking Hsp90, and the investigators have seen signs of disease control in patients with MPN. This study is currently enrolling a cohort expansion for patients with myeloproliferative neoplasms (MPN).
- Being tested
- PU-H71
- Keywords
- PU-H71, Solid Tumor, Lymphoma, 11-041, incurable, locally advanced or metastatic solid tumor malignancy or lymphoma
- Medical subject headings
- Neoplasm Metastasis, Lymphoma, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PU-H71Drug
PU-H71 will be administered as an intravenous infusion over 1 hour two times a week on a 2 week on and 1 week off (Q21 day) schedule with a starting dose of 10 mg/m2. A Cycle on study will be defined as 21 days. The same schedule of administration will be used for all patients in this Phase I trial, and a MCRM (modified continual reassessment method)design will be employed. The MPN expansion may explore different dosing schedules.
| Study group | Role | What they receive |
|---|---|---|
| PU-H71 | Experimental | This Phase 1 trial will be an open-label, dose-escalation study of single-agent PU-H71 in patients with advanced solid malignancies and lymphoma. Receives: Drug: PU-H71 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety of PU-H71 in patients with advanced malignancies.
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. All patients enrolled who receive study drug will be eligible for these analyses.
Measured: 2 years
To assess the tolerability of PU-H71 in patients with advanced malignancies.
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
Measured: 2 years
To assess the pharmacokinetics of PU-H71 in patients with advanced malignancies.
Blood will be drawn at the multiple time points for radioactive pharmacokinetic and metabolite analyses of 124I-PUH71
Measured: The investigators anticipate these time points to be: 5 min (+mins), 3-4, 18-24 and 44-48 hours post-injection.
To determine the maximum tolerated dose (MTD) based on toxicity analysis.
Toxicity will be monitored using NCI- Common Terminology Criteria for Adverse Events version (4.0).Patients receiving at least 3 out of 4 planned doses of study drug developing a drug-related toxicity will be eligible for these analyses.
Measured: 2 years
Secondary outcomes (2)
To assess anti-tumor activity as defined by response rate
complete response (CR), partial response (PR), stable disease (SD), duration of response, and progression free survival (PFS). Patients with measurable disease will be eligible for these analyses.
Measured: 2 years
To evaluate 124I-PU-H71 as a non-invasive means to determine tumor pharmacokinetics and intra-tumoral concentration
In a selected group of patients with advanced malignancies. All patients who undergo planned imaging will be eligible for this analysis.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2011 (estimated)
- Study start6 Jul 2011
- Primary completion23 Mar 2023
- Study completion23 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Solid TumorStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Komal Jhaveri, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01393509
- Sponsor's protocol ID
- 11-041
- Status last verified
- Mar 2023
- First submitted
- 9 Jul 2011
- Last updated
- 28 Mar 2023
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT01393509
- Acronym / sponsor ID
- 11-041
- Keywords
- PU-H71, Solid Tumor, Lymphoma, 11-041, incurable, locally advanced or metastatic solid tumor malignancy or lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 6 Jul 2011 (actual)
- Primary completion
- 23 Mar 2023 (actual)
- Study completion
- 23 Mar 2023 (actual)
- First posted
- 13 Jul 2011 (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.
NOTE: This study is now recruiting only patients with Myeloproliferative Neoplasms (MPN). Dose escalation has been completed.
The purpose of this study is to test a new drug, called PU-H71 for the first time in humans, to find out what effects, good or bad, this new drug has on the patient and the cancer at different dose levels. PU-H71 blocks a protein called Heat Shock Protein-90 (Hsp90). Hsp90 is found in both normal and cancer cells, but may be more important in cancer cells. Attacking Hsp90 can stop the function of certain proteins that are needed for cancer cells to survive. The diseases that are part of this study may be especially sensitive to attacking Hsp90, and the investigators have seen signs of disease control in patients with MPN. This study is currently enrolling a cohort expansion for patients with myeloproliferative neoplasms (MPN).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PU-H71 | Experimental | Drug: PU-H71This Phase 1 trial will be an open-label, dose-escalation study of single-agent PU-H71 in patients with advanced solid malignancies and lymphoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- The safety-expansion phase will be open to accrual only for patients with MPN.
- ≥ 18 years of age
- For patients with solid malignancies and lymphoma, radiographically detectable (Either FDG-PET, CT scan/ MRI or Bone Scan) or measurable disease will be required. Measurable disease is defined as at least one measurable lesion ≥ 10 mm on CT scan (15 mm for nodal lesions).
- Prior therapy for advanced malignancy with no current curative option
- Neutrophil count ≥ 1,000/μL, platelet count ≥ 50,000/μL, and hemoglobin ≥ 8 g/dL (Platelet count must be assessed at least 7 days after a prior transfusion, if any)
Key exclusion criteria (11 listed)
- Ejection fraction < 50%, as determined by echocardiogram or MUGA scan
- Symptomatic brain or CNS metastases. Previously treated and stable CNS disease is allowed.
- Any of the following for the treatment of cancer within 2 weeks of first study treatment: chemotherapy, immunotherapy, experimental therapy or biologic therapy.
- Any major surgical procedure or radiation within 4 weeks of first study treatment
- Active liver disease, including viral or other hepatitis, or cirrhosis
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 |
|---|---|---|
| PU-H71PU-H71 will be administered as an intravenous infusion over 1 hour two times a week on a 2 week on and 1 week off (Q21 day) schedule with a starting dose of 10 mg/m2. A Cycle on study will be defined as 21 days. The same schedule of administration will be used for all patients in this Phase I trial, and a MCRM (modified continual reassessment method)design will be employed. The MPN expansion may explore different dosing schedules. | Drug | PU-H71 |
Primary outcome
To assess the safety of PU-H71 in patients with advanced malignancies.
Time frame: 2 years
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. All patients enrolled who receive study drug will be eligible for these analyses.
To assess the tolerability of PU-H71 in patients with advanced malignancies.
Time frame: 2 years
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
To assess the pharmacokinetics of PU-H71 in patients with advanced malignancies.
Time frame: The investigators anticipate these time points to be: 5 min (+mins), 3-4, 18-24 and 44-48 hours post-injection.
Blood will be drawn at the multiple time points for radioactive pharmacokinetic and metabolite analyses of 124I-PUH71
To determine the maximum tolerated dose (MTD) based on toxicity analysis.
Time frame: 2 years
Toxicity will be monitored using NCI- Common Terminology Criteria for Adverse Events version (4.0).Patients receiving at least 3 out of 4 planned doses of study drug developing a drug-related toxicity will be eligible for these analyses.
2 secondary outcomes
To assess anti-tumor activity as defined by response rate
Time frame: 2 years
To evaluate 124I-PU-H71 as a non-invasive means to determine tumor pharmacokinetics and intra-tumoral concentration
Time frame: 2 years
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 28 Mar 2023.
- Memorial Sloan Kettering Cancer CenterLink 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.
Komal Jhaveri, MD principal investigator
Memorial Sloan Kettering Cancer Center
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 PU-H71 in people with Metastatic Solid Tumor and Lymphoma, run by Memorial Sloan Kettering Cancer Center 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 19 inclusion and 11 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 28 Mar 2023. 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?
To assess the safety of PU-H71 in patients with advanced malignancies. (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Mar 2023.