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NCT01581541

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

Terminated Phase 1 Results posted Last updated 4 October 2017
What this trial tests

Phase 1 trial testing PU-H71 in Solid Tumors in 17 participants. Terminated before completion.

Timeline
26 April 2011
Primary endpoint
3 September 2014
3 September 2014

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment17
Start date26 April 2011
Primary completion3 September 2014
Estimated completion3 September 2014
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 120, any sex, with Solid Tumors or Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Cycle 1 Dose-limiting Toxicities (DLTs) Primary · Cycle 1 (21 days)

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.

GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^20
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^20
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug Primary · 3 years and two months and 11 days

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.

Grade 2 Anemia
GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^21
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^21
PU-H71, 470 mg/m^20
Grade 2 Aspartate Aminotransferase
GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^21
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^20
Grade 2 Atrioventricular Block First Degree
GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^20
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^21
PU-H71, 470 mg/m^20
Grade 2 Blood Bilirubin Increased
GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^21
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^20
Grade 2 Fatigue
GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^20
PU-H71, 150 mg/m^21
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^20
Grade 2 Headache
GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^20
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^21
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^20
Grade 2 Lymphopenia
GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^21
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^20
Grade 2 Nausea
GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^20
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^21
Maximum Tolerated Dose (MTD) of PU-H71 Primary · Cycle 1 (21 days)

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.

GroupValue95% CI
PU-H71NA
Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) Secondary · Baseline and every 6 weeks up to 18 weeks

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 Res

GroupValue95% CI
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^20
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^20
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^20
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^20
PU-H71, 10 mg/m^20
PU-H71, 20 mg/m^20
PU-H71, 40 mg/m^20
PU-H71, 60 mg/m^21
PU-H71, 80 mg/m^20
PU-H71, 110 mg/m^22
PU-H71, 150 mg/m^21
PU-H71, 200 mg/m^21
PU-H71, 266 mg/m^21
PU-H71, 354 mg/m^20
PU-H71, 470 mg/m^20
PU-H71, 10 mg/m^21
PU-H71, 20 mg/m^21
PU-H71, 40 mg/m^21
PU-H71, 60 mg/m^20
PU-H71, 80 mg/m^21
PU-H71, 110 mg/m^21
PU-H71, 150 mg/m^20
PU-H71, 200 mg/m^20
PU-H71, 266 mg/m^20
PU-H71, 354 mg/m^22
PU-H71, 470 mg/m^21
Number of Days on Treatment Secondary · up to 126 days
GroupValue95% CI
PU-H71, 10 mg/m^24242 – 42
PU-H71, 20 mg/m^24242 – 42
PU-H71, 40 mg/m^24242 – 42
PU-H71, 60 mg/m^28484 – 84
PU-H71, 80 mg/m^24242 – 42
PU-H71, 110 mg/m^212642 – 126
PU-H71, 150 mg/m^28484 – 84
PU-H71, 200 mg/m^28484 – 84
PU-H71, 266 mg/m^26363 – 63
PU-H71, 354 mg/m^24242 – 42
PU-H71, 470 mg/m^24242 – 42
Maximum Observed Plasma Concentration (Cmax) Secondary · 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.

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

GroupValue95% CI
PU-H71, 10 mg/m^20.2± 0
PU-H71, 20 mg/m^20.3± 0
PU-H71, 40 mg/m^274.7± 0
PU-H71, 60 mg/m^21.3± 0
PU-H71, 80 mg/m^25.17± 0.1
PU-H71, 110 mg/m^27.3± 2.4
PU-H71, 150 mg/m^28.7± 0
PU-H71, 200 mg/m^28.0± 4.5
PU-H71, 266 mg/m^27.8± 0
PU-H71, 354 mg/m^217.3± 8.5
PU-H71, 470 mg/m^233.7± 0
Terminal Half-life (T1/2) Secondary · 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.

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

GroupValue95% CI
PU-H71, 10 mg/m^22.7± 0
PU-H71, 20 mg/m^210.5± 0
PU-H71, 40 mg/m^29.2± 0
PU-H71, 60 mg/m^26.1± 0
PU-H71, 80 mg/m^26.7± 0.1
PU-H71, 110 mg/m^27.6± 0.2
PU-H71, 150 mg/m^27.2± 0
PU-H71, 200 mg/m^27.1± 0.5
PU-H71, 266 mg/m^210.2± 0
PU-H71, 354 mg/m^211.5± 7.3
PU-H71, 470 mg/m^210.8± 0
Area Under the Concentration-Time Curve From Time 0 to 24 Hours [AUC(0-24)] Secondary · 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 was estimated by trapezoidal rule calculations

GroupValue95% CI
PU-H71, 10 mg/m^227± 0
PU-H71, 20 mg/m^274± 0
PU-H71, 40 mg/m^23845± 0
PU-H71, 60 mg/m^2273± 0
PU-H71, 80 mg/m^2899± 32
PU-H71, 110 mg/m^21186± 481
PU-H71, 150 mg/m^21534± 0
PU-H71, 200 mg/m^22090± 459
PU-H71, 266 mg/m^23596± 0
PU-H71, 354 mg/m^26866± 2876
PU-H71, 470 mg/m^28568± 0
Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] Secondary · 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 was estimated by trapezoidal rule calculations

GroupValue95% CI
PU-H71, 10 mg/m^231± 0
PU-H71, 20 mg/m^2100± 0
PU-H71, 40 mg/m^23905± 0
PU-H71, 60 mg/m^2301± 0
PU-H71, 80 mg/m^21007± 32
PU-H71, 110 mg/m^21375± 591
PU-H71, 150 mg/m^21771± 0
PU-H71, 200 mg/m^22477± 429
PU-H71, 266 mg/m^25449± 0
PU-H71, 354 mg/m^210815± 5499
PU-H71, 470 mg/m^212151± 0
Urinary Excretion (%) Secondary · Every void post-treatment on day 1 of cycle 1

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

GroupValue95% CI
PU-H71, 10 mg/m^25.5± 0
PU-H71, 20 mg/m^2NA± NA
PU-H71, 40 mg/m^21.9± 0
PU-H71, 60 mg/m^28.8± 0
PU-H71, 80 mg/m^26.7± 1.3
PU-H71, 110 mg/m^26.7± 4.6
PU-H71, 150 mg/m^28.1± 0
PU-H71, 200 mg/m^26.0± 4.2
PU-H71, 266 mg/m^25.4± 0
PU-H71, 354 mg/m^28.6± 4.6
PU-H71, 470 mg/m^25.7± 0
Clearance Secondary · 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.

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

GroupValue95% CI
PU-H71, 10 mg/m^21.03± 0
PU-H71, 20 mg/m^20.63± 0
PU-H71, 40 mg/m^20.03± 0
PU-H71, 60 mg/m^20.63± 0
PU-H71, 80 mg/m^20.25± 0.01
PU-H71, 110 mg/m^20.28± 0.12
PU-H71, 150 mg/m^20.27± 0
PU-H71, 200 mg/m^20.26± 0.04
PU-H71, 266 mg/m^20.15± 0
PU-H71, 354 mg/m^20.13± 0.09
PU-H71, 470 mg/m^20.12± 0

Adverse events — posted to ClinicalTrials.gov

Time frame: 3 years and two months and 11 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PU-H71, 10 mg/m^2
Serious: 0/1 (0%)
Deaths: 1/1
PU-H71, 20 mg/m^2
Serious: 1/1 (100%)
Deaths: 0/1
PU-H71, 40 mg/m^2
Serious: 0/1 (0%)
Deaths: 1/1
PU-H71, 60 mg/m^2
Serious: 0/1 (0%)
Deaths: 1/1
PU-H71, 80 mg/m^2
Serious: 0/2 (0%)
Deaths: 0/2
PU-H71, 110 mg/m^2
Serious: 0/3 (0%)
Deaths: 0/3
PU-H71, 150 mg/m^2
Serious: 0/1 (0%)
Deaths: 0/1
PU-H71, 200 mg/m^2
Serious: 0/2 (0%)
Deaths: 0/2
PU-H71, 266 mg/m^2
Serious: 0/1 (0%)
Deaths: 1/1
PU-H71, 354 mg/m^2
Serious: 1/3 (33%)
Deaths: 0/3
PU-H71, 470 mg/m^2
Serious: 1/1 (100%)
Deaths: 0/1

Serious adverse events (5 terms)

ReactionSystemPU-H71, 10 mg/m^2PU-H71, 20 mg/m^2PU-H71, 40 mg/m^2PU-H71, 60 mg/m^2PU-H71, 80 mg/m^2PU-H71, 110 mg/m^2PU-H71, 150 mg/m^2PU-H71, 200 mg/m^2PU-H71, 266 mg/m^2PU-H71, 354 mg/m^2PU-H71, 470 mg/m^2
Atrioventricular block first degreeCardiac disorders———————————
Lung InfectionInfections and infestations———————————
NauseaGastrointestinal disorders———————————
Sinus bradycardiaCardiac disorders———————————
VomitingGastrointestinal disorders———————————
Other adverse events (82 terms — click to expand)

ReactionSystemPU-H71, 10 mg/m^2PU-H71, 20 mg/m^2PU-H71, 40 mg/m^2PU-H71, 60 mg/m^2PU-H71, 80 mg/m^2PU-H71, 110 mg/m^2PU-H71, 150 mg/m^2PU-H71, 200 mg/m^2PU-H71, 266 mg/m^2PU-H71, 354 mg/m^2PU-H71, 470 mg/m^2
DiarrheaGastrointestinal disorders———————————
HypertensionVascular disorders———————————
Alkaline phosphatase increasedInvestigations———————————
AnemiaBlood and lymphatic system disorders———————————
Aspartate aminotransferase increasedInvestigations———————————
HypoalbuminemiaMetabolism and nutrition disorders———————————
Lymphocyte count decreasedInvestigations———————————
NauseaGastrointestinal disorders———————————
Sinus tachycardiaCardiac disorders———————————
Abdominal pain - crampingGastrointestinal disorders———————————
Abdominal painGastrointestinal disorders———————————
Activated partial thromboplastin time prolongedInvestigations———————————
Alanine aminotransferase increasedInvestigations———————————
AnorexiaMetabolism and nutrition disorders———————————
AnxietyPsychiatric disorders———————————
BloatingGastrointestinal disorders———————————
Blood bilirubin increasedInvestigations———————————
Blurred visionEye disorders———————————
ChillsGeneral disorders———————————
ConfusionPsychiatric disorders———————————
ConstipationGastrointestinal disorders———————————
CoughRespiratory, thoracic and mediastinal disorders———————————
CPK increasedInvestigations———————————
Creatinine increasedInvestigations———————————
DehydrationMetabolism and nutrition disorders———————————
DizzinessNervous system disorders———————————
Dry eyeEye disorders———————————
DyspneaRespiratory, thoracic and mediastinal disorders———————————
Electrocardiogram QT corrected interval prolongedInvestigations———————————
Eye painEye disorders———————————
FatigueGeneral disorders———————————
FeverGeneral disorders———————————
Flank pain - LeftMusculoskeletal and connective tissue disorders———————————
FlushingVascular disorders———————————
Gastroesophageal reflux diseaseGastrointestinal disorders———————————
HeadacheNervous system disorders———————————
HematuriaRenal and urinary disorders———————————
HemoglobinuriaRenal and urinary disorders———————————
HemorrhoidsGastrointestinal disorders———————————
HiccupsRespiratory, thoracic and mediastinal disorders———————————

Most-reported serious reactions: Atrioventricular block first degree, Lung Infection, Nausea, Sinus bradycardia, Vomiting.

Data from ClinicalTrials.gov NCT01581541 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Heat shock protein 90 inhibitors in the treatment of cancer: current status and future directions.
    Jhaveri K, Ochiana SO, Dunphy MP, Gerecitano JF, et al · · 2014 · cited 128× · PMID 24669860 · DOI 10.1517/13543784.2014.902442
  2. HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review).
    Li ZN, Luo Y. · · 2023 · cited 118× · PMID 36367182 · DOI 10.3892/or.2022.8443
  3. Combinatorial targeting of nuclear export and translation of RNA inhibits aggressive B-cell lymphomas.
    Culjkovic-Kraljacic B, Fernando TM, Marullo R, Calvo-Vidal N, et al · · 2016 · cited 80× · PMID 26603836 · DOI 10.1182/blood-2015-05-645069
  4. A Hyperactive Signalosome in Acute Myeloid Leukemia Drives Addiction to a Tumor-Specific Hsp90 Species.
    Zong H, Gozman A, Caldas-Lopes E, Taldone T, et al · · 2015 · cited 58× · PMID 26628369 · DOI 10.1016/j.celrep.2015.10.073
  5. Heat shock protein 90: biological functions, diseases, and therapeutic targets.
    Wei H, Zhang Y, Jia Y, Chen X, et al · · 2024 · cited 54× · PMID 38283176 · DOI 10.1002/mco2.470
  6. First-in-human study of the epichaperome inhibitor PU-H71: clinical results and metabolic profile.
    Speranza G, Anderson L, Chen AP, Do K, et al · · 2018 · cited 39× · PMID 28808818 · DOI 10.1007/s10637-017-0495-3
  7. Prodigiosin/PU-H71 as a novel potential combined therapy for triple negative breast cancer (TNBC): preclinical insights.
    Anwar MM, Shalaby M, Embaby AM, Saeed H, et al · · 2020 · cited 37× · PMID 32895397 · DOI 10.1038/s41598-020-71157-w
  8. HSP90 multi-functionality in cancer.
    Albakova Z. · · 2024 · cited 32× · PMID 39148727 · DOI 10.3389/fimmu.2024.1436973

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01581541.

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