The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies

This study is currently recruiting participants.
Verified February 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01393509
First received: July 9, 2011
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

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, but the investigators do not know if PU-H71 will have any effect on the disease.


Condition Intervention Phase
Metastatic Solid Tumor
Lymphoma
Drug: PU-H71
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The First-in-human Phase I Trial of PU-H71 in Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To assess the safety of PU-H71 in patients with advanced malignancies. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.

  • To assess the tolerability of PU-H71 in patients with advanced malignancies. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Toxicity will be monitored using NCI- Common Terminology Criteria for Adverse Events version (4.0). Patients receiving at least one cycle of drug, or developing a drug-related toxicity will be eligible for these analyses.


Secondary Outcome Measures:
  • To assess anti-tumor activity as defined by response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.

  • To evaluate 124I-PU-H71 as a non-invasive means to determine tumor pharmacokinetics and intra-tumoral concentration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    In a selected group of patients with advanced malignancies. All patients who undergo planned imaging will be eligible for this analysis.


Estimated Enrollment: 40
Study Start Date: July 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PU-H71
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.
Drug: PU-H71
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically documented (Pathology confirmed at MSKCC), incurable, locally advanced or metastatic solid tumor malignancy or lymphoma; the safety-expansion phase will be open to accrual only for patients with MPN.
  • ≥ 18 years of age
  • Radiographically detectable (Either FDG-PET, CT scan/ MRI or Bone Scan) or measurable disease. Measurable disease is defined as at least one measurable lesion ≥ 1 cm on CT scan .
  • Prior therapy for advanced malignancy with no current curative option
  • Neutrophil count ≥ 1,000/μL, platelet count ≥ 75,000/μL, and hemoglobin ≥ 9 g/dL (hematologic parameters must be assessed at least 14 days after a prior transfusion, if any)
  • Serum bilirubin ≤ 1.5 mg/dL;
  • 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
  • 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.
  • Signed written informed consent and HIPAA consent.

Exclusion Criteria:

  • 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, radiotherapy, immunotherapy, experimental therapy or biologic therapy.

  • Any major surgical procedure or radiation within 4 weeks of first study treatment
  • History of clinically symptomatic liver disease, including viral or other hepatitis, or cirrhosis
  • Pregnancy or lactation
  • 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 QTc > 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01393509

Contacts
Contact: John Gerecitano, MD, PhD 212-639-3748
Contact: Shanu Modi, MD 646-888-5243

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: John Gerecitano, MD, PhD    212-639-3748      
Contact: Shanu Modi, MD    646-888-5243      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: John Gerecitano, MD,PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01393509     History of Changes
Other Study ID Numbers: 11-041
Study First Received: July 9, 2011
Last Updated: February 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
PU-H71
Solid Tumor
Lymphoma
11-041
incurable, locally advanced or metastatic solid tumor malignancy or lymphoma

Additional relevant MeSH terms:
Neoplasms
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014