TerminatedNCT01581541Updated Oct 4, 2017Results posted

PU-H71 in Patients With Solid Tumors and Low-Grade Non-Hodgkin's Lymphoma That Have Not Responded to Standard Treatment

A Phase 1 interventional study of PU-H71 in Solid Tumors and Lymphoma, sponsored by National Cancer Institute (NCI). Terminated at 1 site in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2017-10-04.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Why this study was terminated

The study closed prematurely due to discontinuation of drug supply.

From the registry’s dates

Registered 11 months after the study started (first participant enrolled Apr 2011, registered Apr 2012).

Phase: Phase 1
Study type: Interventional
Enrollment: 17
Allocation: Non-randomized
Ages: 18 Years to 120 Years
Sex: All

Study summary

Background:

PU-H71 is an experimental drug used to treat cancer. It works by blocking a protein in tumors. When this protein is blocked, it affects other proteins inside the cell that cancers need to grow. Researchers want to study whether PU-H71 is a safe and effective way to treat solid tumors and non-Hodgkin's lymphoma.

Objectives:

To evaluate the safety and effectiveness of PU-H71 in solid tumors and non-Hodgkin's lymphoma that have not responded to standard treatments.

Eligibility:

Individuals at least 18 years of age who have solid tumors or non-Hodgkin's lymphoma that have not responded to standard treatments.

Design:

Patients will be screened with a physical exam, medical history, blood tests, and imaging studies.
Patients will receive PU-H71 as a 1-hour dose on days 1 and 8 of a 21-day cycle of treatment. The first treatment cycle will be done in the hospital so that patients can be monitored. The next treatment cycles will be done on an outpatient basis.
Patients will have blood and urine tests and eye exams.
Patients will provide tumor samples for study.
Patients will have imaging studies to monitor tumor response to treatment.
Patients will continue to take PU-H71 for as long as side effects remain tolerable and their tumor or lymphoma does not worsen. Study researchers may adjust the dose if needed.

Read the detailed description

Background:

-PU-H71 is a synthetic HSP90 inhibitor which can bind both open and closed conformations of HSP90. It demonstrates extended tumor retention and client protein degradation, while being rapidly cleared from normal tissues. It has shown complete tumor responses and retained sensitivity to retreatment in vivo.

Primary Objectives:

To establish the safety and tolerability of PU-H71 administered on a once weekly, 2 weeks out of 3 schedule, in patients with refractory solid tumors and lowgrade non-Hodgkin's lymphoma (NHL).
To establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of PU-H71 administered on a once weekly, 2 weeks out of 3 schedule, in patients with refractory solid tumors and low-grade NHL.
To determine the pharmacokinetics of PU-H71 administered on a once weekly, 2 weeks out of 3 schedule, in patients with refractory solid tumors and low-grade NHL.

Secondary Objectives:

To perform pharmacodynamic studies to ascertain PU-H71 effect on HSP70 in tumor tissue, serum, and peripheral blood mononuclear cells (PBMCs) at the MTD.
To perform pharmacodynamic studies to ascertain PU-H71 effect on HSP90 client proteins in tumor tissue at the MTD.

Eligibility:

-Study participants must have histologically confirmed solid tumor malignancy or low-grade non-Hodgkin s lymphoma that has progressed or recurred after at least one line of chemotherapy or for which no standard treatment option exists; no therapy within 4 weeks prior to entering the study; age greater than or equal to 18 years; Eastern Cooperative Oncology Group (ECOG) less than or equal to 2; life expectancy > 3 months; and adequate organ and marrow function. Patients entering on the expansion cohort at the MTD must have disease amenable to biopsy with willingness to undergo pre- and post-treatment biopsies.

Study Design:

This study will follow a modified accelerated titration design (Simon et al., 1997).
The accelerated phase ends when 1 patient experiences a dose-limiting toxicity or 2 patients experience Grade 2 drug-related toxicity during the first cycle; after which the study will follow the standard 3 + 3 design.
PU-H71 will be administered intravenously over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days.
Pharmacokinetics (PK) and pharmacodynamics (PD) studies will be conducted during cycle 1. Up to 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.
Computed tomography (CT) scans will be performed at baseline and every 2 cycles (6 weeks) for restaging.
Up to 100 patients may be treated.

Conditions studied

Solid Tumors
Lymphoma

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Keywords

Targeted Therapy
Solid Tumors
Lymphoma
Non-Hodgkin Lymphoma
Solid Tumor

In context

Lymphoma

5,577 studies on the registry are indexed under Lymphoma; 824 are open to participants now.

This study's enrollment of 17 is below the median of 40 across 4,507 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 120 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Patients must have histologically documented (confirmed at the Laboratory of Pathology, National Cancer Institute (NCI)) solid tumor malignancy or low-grade non-Hodgkin's lymphoma that is metastatic or unresectable, for which standard curative measures do not exist, or whose disease has progressed or recurred following 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 a Phase 0 study (also referred to as a pre-Phase I study where a sub-therapeutic dose of drug is administered). 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.
An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
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 upper limit of normal (ULN)
- Aspartate aminotransferase (AST)serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(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 PU-H71 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 she or her partner is participating in the study, the treating physician should be notified immediately. Because there is an unknown but potential risk to nursing infants secondary to treatment of the mother with PU-H71, breastfeeding should be discontinued if the mother is treated with PU-H71.
During the expansion phase of the protocol, patients must have:
- Disease amenable to biopsy
- Willingness to undergo pre- and post-treatment tumor biopsies
Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

EXCLUSION CRITERIA:

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 3 months after treatment of the brain metastases.
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.
Corrected QT interval (QTc) > 450 msec for men and > 470 msec for women.
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetics (PK) interactions with PU-H71.
Pregnant women are ineligible because the effects of PU-H71 on the developing human fetus are unknown. Breastfeeding should be discontinued if the mother is treated with PU-H71 since there is an unknown but potential risk for adverse events in nursing infants.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 17 participants (actual)

Study arms

Experimental
PU-H71
PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
Drug: PU-H71

Interventions

DrugPU-H71
PU-H71 is a synthetic HSP90 inhibitor which can bind both open and closed conformations of HSP90. It demonstrates extended tumor retention and client protein degradation, while being rapidly cleared from normal tissues. It has shown complete tumor responses and retained sensitivity to retreatment in vivo.

What researchers measure

Primary outcomes

Number of Participants With Cycle 1 Dose-limiting Toxicities (DLTs)
A DLT was defined as an adverse event that occurred during cycle 1, was thought to be related to study drug administration, and met one of the following criteria: grade ≥ 3 non-hematologic toxicities (except diarrhea, nausea, vomiting without maximal supportive therapy; alopecia), grade 4 hematologic toxicities (except lymphopenia), and grade 2 ocular toxicity that did not resolve to ≤ grade 1 within 2 weeks. Occurrence of a DLT resulted in a dose reduction following resolution to grade ≤ 2. No more than 2 dose reductions were allowed per patient on study.
Time frame: Cycle 1 (21 days)
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug
Severity of adverse events were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1 Mild adverse event (AE), Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, and Grade 5 Death related to AE.
Time frame: 3 years and two months and 11 days
Maximum Tolerated Dose (MTD) of PU-H71
The MTD is the dose level at which no more than 1 of 6 patients experience DLT during the first cycle of treatment, and the dose below that at which at least 2 (of ≤ 6) patients have DLT as a result of the drug.
Time frame: Cycle 1 (21 days)

Secondary outcomes

Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Number of Participants According to Best Response Per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by computed tomography (CT): Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.
Time frame: Baseline and every 6 weeks up to 18 weeks
Number of Days on Treatment
Time frame: up to 126 days
Maximum Observed Plasma Concentration (Cmax)
The maximum concentration (Cmax) was determined by visual inspection of the concentration versus time data.
Time frame: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.
Terminal Half-life (T1/2)
The terminal half-life (t1/2) was derived from the plasma concentration vs. time data.
Time frame: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.
Area Under the Concentration-Time Curve From Time 0 to 24 Hours [AUC(0-24)]
Area Under the Concentration-Time Curve From Time 0 to 24 Hours was estimated by trapezoidal rule calculations
Time frame: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.
Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)]
Area Under the Concentration-Time Curve From Time 0 to Infinity was estimated by trapezoidal rule calculations
Time frame: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.
Urinary Excretion (%)
Elimination of the drug was investigated by analysis of an aliquot of the total urine collected in 24 h.
Time frame: Every void post-treatment on day 1 of cycle 1
Clearance
Clearance was calculated from drug dose and AUC(0-∞).
Time frame: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.

Results

Posted Oct 4, 2017

Participant flow

Participant flow — Overall Study
Milestone	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Started	1	1	1	1	2	3	1	2	1	3	1
Completed	1	1	1	1	2	3	1	2	1	3	1
Not completed	0	0	0	0	0	0	0	0	0	0	0

Outcome measures

PrimaryNumber of Participants With Cycle 1 Dose-limiting Toxicities (DLTs)

A DLT was defined as an adverse event that occurred during cycle 1, was thought to be related to study drug administration, and met one of the following criteria: grade ≥ 3 non-hematologic toxicities (except diarrhea, nausea, vomiting without maximal supportive therapy; alopecia), grade 4 hematologic toxicities (except lymphopenia), and grade 2 ocular toxicity that did not resolve to ≤ grade 1 within 2 weeks. Occurrence of a DLT resulted in a dose reduction following resolution to grade ≤ 2. No more than 2 dose reductions were allowed per patient on study.

Time frame:: Cycle 1 (21 days)
Reported as:: Count of participants · Participants

Number of Participants With Cycle 1 Dose-limiting Toxicities (DLTs)
Participants	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Number of Participants With Cycle 1 Dose-limiting Toxicities (DLTs)	0	0	0	0	0	0	0	0	0	0	0

PrimaryNumber of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug

Severity of adverse events were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1 Mild adverse event (AE), Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, and Grade 5 Death related to AE.

Time frame:: 3 years and two months and 11 days
Reported as:: Count of participants · Participants

Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug
Participants	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Grade 2 Anemia	1	0	0	1	0
Grade 2 Aspartate Aminotransferase	1	0	0	0	0
Grade 2 Atrioventricular Block First Degree	0	0	0	1	0
Grade 2 Blood Bilirubin Increased	1	0	0	0	0
Grade 2 Fatigue	0	1	0	0	0
Grade 2 Headache	0	0	1	0	0
Grade 2 Lymphopenia	1	0	0	0	0
Grade 2 Nausea	0	0	0	0	1
Grade 2 Sinus Bradycardia	0	0	0	1	0
Grade 3 Vomiting	0	0	0	0	1

PrimaryMaximum Tolerated Dose (MTD) of PU-H71

The MTD is the dose level at which no more than 1 of 6 patients experience DLT during the first cycle of treatment, and the dose below that at which at least 2 (of ≤ 6) patients have DLT as a result of the drug.

Time frame:: Cycle 1 (21 days)
Reported as:: Number · mg/m^2

Maximum Tolerated Dose (MTD) of PU-H71
mg/m^2	PU-H71
Maximum Tolerated Dose (MTD) of PU-H71	NA

SecondaryNumber of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)

Number of Participants According to Best Response Per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by computed tomography (CT): Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions.

Time frame:: Baseline and every 6 weeks up to 18 weeks
Reported as:: Count of participants · Participants

Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Participants	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Complete Response	0	0	0	0	0	0	0	0	0	0	0
Partial Response	0	0	0	0	0	0	0	0	0	0	0
Stable Disease	0	0	0	1	0	2	1	1	1	0	0
Progression of Disease	1	1	1	0	1	1	0	0	0	2	1

SecondaryNumber of Days on Treatment

Time frame:: up to 126 days
Reported as:: Median · days

Number of Days on Treatment
days	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Number of Days on Treatment	42 (42 to 42)	42 (42 to 42)	42 (42 to 42)	84 (84 to 84)	42 (42 to 42)	126 (42 to 126)	84 (84 to 84)	84 (84 to 84)	63 (63 to 63)	42 (42 to 42)	42 (42 to 42)

SecondaryMaximum Observed Plasma Concentration (Cmax)

The maximum concentration (Cmax) was determined by visual inspection of the concentration versus time data.

Time frame:: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.
Reported as:: Mean · µM

Maximum Observed Plasma Concentration (Cmax)
µM	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Maximum Observed Plasma Concentration (Cmax)	0.2 ± 0	0.3 ± 0	74.7 ± 0	1.3 ± 0	5.17 ± 0.1	7.3 ± 2.4	8.7 ± 0	8.0 ± 4.5	7.8 ± 0	17.3 ± 8.5	33.7 ± 0

SecondaryTerminal Half-life (T1/2)

The terminal half-life (t1/2) was derived from the plasma concentration vs. time data.

Time frame:: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.
Reported as:: Mean · hours

Terminal Half-life (T1/2)
hours	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Terminal Half-life (T1/2)	2.7 ± 0	10.5 ± 0	9.2 ± 0	6.1 ± 0	6.7 ± 0.1	7.6 ± 0.2	7.2 ± 0	7.1 ± 0.5	10.2 ± 0	11.5 ± 7.3	10.8 ± 0

SecondaryArea Under the Concentration-Time Curve From Time 0 to 24 Hours [AUC(0-24)]

Area Under the Concentration-Time Curve From Time 0 to 24 Hours was estimated by trapezoidal rule calculations

Time frame:: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.
Reported as:: Mean · µM*min

Area Under the Concentration-Time Curve From Time 0 to 24 Hours [AUC(0-24)]
µM*min	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Area Under the Concentration-Time Curve From Time 0 to 24 Hours [AUC(0-24)]	27 ± 0	74 ± 0	3845 ± 0	273 ± 0	899 ± 32	1186 ± 481	1534 ± 0	2090 ± 459	3596 ± 0	6866 ± 2876	8568 ± 0

SecondaryArea Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)]

Area Under the Concentration-Time Curve From Time 0 to Infinity was estimated by trapezoidal rule calculations

Time frame:: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.
Reported as:: Mean · µM*min

Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)]
µM*min	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)]	31 ± 0	100 ± 0	3905 ± 0	301 ± 0	1007 ± 32	1375 ± 591	1771 ± 0	2477 ± 429	5449 ± 0	10815 ± 5499	12151 ± 0

SecondaryUrinary Excretion (%)

Elimination of the drug was investigated by analysis of an aliquot of the total urine collected in 24 h.

Time frame:: Every void post-treatment on day 1 of cycle 1
Reported as:: Mean · percent of dose recovered

Urinary Excretion (%)
percent of dose recovered	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Urinary Excretion (%)	5.5 ± 0	NA ± NA	1.9 ± 0	8.8 ± 0	6.7 ± 1.3	6.7 ± 4.6	8.1 ± 0	6.0 ± 4.2	5.4 ± 0	8.6 ± 4.6	5.7 ± 0

SecondaryClearance

Clearance was calculated from drug dose and AUC(0-∞).

Time frame:: Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.
Reported as:: Mean · L/h/kg

Clearance
L/h/kg	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Clearance	1.03 ± 0	0.63 ± 0	0.03 ± 0	0.63 ± 0	0.25 ± 0.01	0.28 ± 0.12	0.27 ± 0	0.26 ± 0.04	0.15 ± 0	0.13 ± 0.09	0.12 ± 0

Adverse events

Collected over 3 years and two months and 11 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
PU-H71, 10 mg/m^2	1/1 (100%)	0/1 (0%)	1/1 (100%)
PU-H71, 20 mg/m^2	0/1 (0%)	1/1 (100%)	1/1 (100%)
PU-H71, 40 mg/m^2	1/1 (100%)	0/1 (0%)	1/1 (100%)
PU-H71, 60 mg/m^2	1/1 (100%)	0/1 (0%)	1/1 (100%)
PU-H71, 80 mg/m^2	0/2 (0%)	0/2 (0%)	2/2 (100%)
PU-H71, 110 mg/m^2	0/3 (0%)	0/3 (0%)	3/3 (100%)
PU-H71, 150 mg/m^2	0/1 (0%)	0/1 (0%)	1/1 (100%)
PU-H71, 200 mg/m^2	0/2 (0%)	0/2 (0%)	2/2 (100%)
PU-H71, 266 mg/m^2	1/1 (100%)	0/1 (0%)	1/1 (100%)
PU-H71, 354 mg/m^2	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
PU-H71, 470 mg/m^2	0/1 (0%)	1/1 (100%)	1/1 (100%)

Most frequent serious events

Most frequent serious events
Event	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Lung InfectionInfections and infestations	0/1	1/1	0/1	0/1	0/2	0/3	0/1	0/2	0/1	0/3	0/1
NauseaGastrointestinal disorders	0/1	0/1	0/1	0/1	0/2	0/3	0/1	0/2	0/1	0/3	1/1
VomitingGastrointestinal disorders	0/1	0/1	0/1	0/1	0/2	0/3	0/1	0/2	0/1	0/3	1/1
Atrioventricular block first degreeCardiac disorders	0/1	0/1	0/1	0/1	0/2	0/3	0/1	0/2	0/1	1/3	0/1
Sinus bradycardiaCardiac disorders	0/1	0/1	0/1	0/1	0/2	0/3	0/1	0/2	0/1	1/3	0/1

Most frequent other events

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Most frequent other events
Event	PU-H71, 10 mg/m^2	PU-H71, 20 mg/m^2	PU-H71, 40 mg/m^2	PU-H71, 60 mg/m^2	PU-H71, 80 mg/m^2	PU-H71, 110 mg/m^2	PU-H71, 150 mg/m^2	PU-H71, 200 mg/m^2	PU-H71, 266 mg/m^2	PU-H71, 354 mg/m^2	PU-H71, 470 mg/m^2
Abdominal pain - crampingGastrointestinal disorders	0/1	0/1	0/1	0/1	0/2	0/3	1/1	0/2	0/1	1/3	0/1
Abdominal painGastrointestinal disorders	0/1	0/1	0/1	1/1	0/2	0/3	1/1	0/2	0/1	0/3	0/1
Activated partial thromboplastin time prolongedInvestigations	0/1	0/1	1/1	0/1	0/2	0/3	0/1	0/2	0/1	0/3	0/1
Alanine aminotransferase increasedInvestigations	0/1	0/1	0/1	1/1	0/2	1/3	0/1	1/2	0/1	1/3	1/1
Alkaline phosphatase increasedInvestigations	0/1	0/1	0/1	0/1	1/2	2/3	1/1	0/2	0/1	0/3	0/1
AnemiaBlood and lymphatic system disorders	0/1	0/1	1/1	1/1	1/2	2/3	0/1	1/2	0/1	2/3	1/1
AnorexiaMetabolism and nutrition disorders	0/1	1/1	0/1	0/1	1/2	0/3	0/1	0/2	1/1	1/3	1/1
AnxietyPsychiatric disorders	0/1	0/1	0/1	0/1	0/2	0/3	1/1	0/2	0/1	0/3	0/1
Aspartate aminotransferase increasedInvestigations	1/1	0/1	0/1	1/1	0/2	2/3	0/1	2/2	0/1	1/3	0/1
Blood bilirubin increasedInvestigations	0/1	0/1	0/1	0/1	1/2	1/3	1/1	0/2	0/1	0/3	0/1

Baseline characteristics

Age, Continuous
Age, Continuous(years)	PU-H71
Median	59 (19 to 77)

Sex: Female, Male
Sex: Female, Male(Participants)	PU-H71
Female	7
Male	10

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	PU-H71
Hispanic or Latino	1
Not Hispanic or Latino	16
Unknown or Not Reported	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	PU-H71
American Indian or Alaska Native	0
Asian	1
Native Hawaiian or Other Pacific Islander	0
Black or African American	4
White	11
More than one race	0
Unknown or Not Reported	1

Region of Enrollment
Region of Enrollment(participants)	PU-H71
United States	17

Number of Prior Therapies
Number of Prior Therapies(prior therapies)	PU-H71
Mean	7 (1 to 14)

Diagnosis
Diagnosis(Participants)	PU-H71
Malignant Hürthle cell tumor	1
Rectal adenocarcinoma	1
Adenocarcinoma, not otherwise specified	6
Adenoid cystic carcinoma	1
Invasive poorly differentiated carcinoma	1
Metastatic adenocarcinoma	1
Hepatocellular carcinoma	1
Carcinoid tumor	1
Squamous cell carcinoma of the esophagus	1
Synovial sarcoma	2
Non-small cell lung cancer	1

Study locations

1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland 20892, United States

References and documents

Publications

Zuehlke A, Johnson JL. Hsp90 and co-chaperones twist the functions of diverse client proteins. Biopolymers. 2010 Mar;93(3):211-7. doi: 10.1002/bip.21292. PubMed 19697319 ↗
Fukuyo Y, Hunt CR, Horikoshi N. Geldanamycin and its anti-cancer activities. Cancer Lett. 2010 Apr 1;290(1):24-35. doi: 10.1016/j.canlet.2009.07.010. Epub 2009 Oct 21. PubMed 19850405 ↗
Chavany C, Mimnaugh E, Miller P, Bitton R, Nguyen P, Trepel J, Whitesell L, Schnur R, Moyer J, Neckers L. p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2. J Biol Chem. 1996 Mar 1;271(9):4974-7. doi: 10.1074/jbc.271.9.4974. PubMed 8617772 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 4, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01581541
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Alice Chen, M.D. (Principal Investigator, National Institutes of Health Clinical Center (CC)) — Principal investigator
First posted: Apr 20, 2012
Start date: Apr 26, 2011
Primary completion: Sep 3, 2014
Completion: Sep 3, 2014
Results posted: Oct 4, 2017
Last update: Oct 4, 2017

Study contacts

Alice P Chen, M.D.

principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Sep 2017. You cannot join it, but the record below documents what was studied.

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