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Study Summary
No. 2005-0990:.......Advanced Cancers; Lymphoma; Solid Tumors......Razelle Kurzrock......Phase I Program
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Study Summary Title
Study Summary
Number:
2005-0990
Study Title:Phase I Clinical Trial of NPI-0052 in Patients with Advanced Solid Tumor Malignancies or Refractory Lymphoma
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Physician New Patient Referral
Name:Razelle KurzrockPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Phase I ProgramReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-1226
Contact us about clinical trials
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General Information
Disease Group:Advanced Cancers
Lymphoma
Solid Tumors
Supported By:N/A
Phase of Study:Phase IReturn
Visit:
Patients will return to the clinic on Days 1, 8, 15 of each cycle; Days 2, 16,
17, 22, and 29 during Cycle 1 only; and 28 days after last dose of treatment
agent.
Treatment
Agents:
NPI-0052Home Care:N/A
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this study is to find the highest tolerable dose of NPI-0052 that
can be given by injection to patients with advanced solid tumors or lymphomas.
Researchers will also study the level of the study drug in the blood at
different times, and how the body breaks down the drug. The safety and
effectiveness of this drug will also be studied.
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Study Objectives / Outcomes
The primary objectives of this study:
  • To determine the maximum tolerated dose (MTD) of NPI-0052 when administered via intravenous infusion to patients with advanced solid tumor malignancies (including lymphoma) on Days 1, 8 and 15 every 4 weeks.
  • To evaluate the blood pharmacokinetics of NPI-0052 when administered on this schedule.

The secondary objectives are to:
  • Evaluate the safety and toxicity profile of repeated dosing of NPI-0052
  • Assess the biological activity and pharmacodynamics of NPI-0052 in patients with these malignancies using a variety of laboratory correlative studies (including proteasome inhibition)
  • Recommend a dose for future study of NPI-0052
  • Describe and assess any preliminary evidence of anti-tumor activity of NPI-0052 using standard response assessment criteria for solid tumors (RECIST) and lymphoma (Cheson et al 2000).
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Study Status Information
Study Activation / Registration Date:05/05/2006
IRB Review and Approval Date:02/15/2006
Study Type:Phase I
Recruitment Status:Closed
Projected Accrual:60
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Male and females: >/= 18 years of age

2) Karnofsky performance status >/= 70%

3) Histologically-confirmed solid tumor malignancy (patients must be refractory to or demonstrate unacceptable toxicity towards effective therapy known to provide clinical benefit for their condition; i.e., patients must not be candidates for regimens known to provide clinical benefit), OR refractory lymphoma (patients whose disease has progressed despite standard therapy,

4) (Inclusion #3 cont'd) including at least one doxorubicin-containing regimen and one anti-CD20 monoclonal antibody-containing regimen as appropriate for the diagnosis. For patients to enroll in the expanded dose group, patients must have measurable disease (by RECIST for solid tumors; by Cheson et al 1999; Pfistner et all 2005 for lymphoma).

5) All adverse events of any prior chemotherapy, surgery or radiotherapy, must have resolved to NCI CTCAE (v. 3.0) Grade </= 1, except for hemoglobin.

6) The following laboratory result, within 7 days (14 days for serum creatinine) of NPI-0052 administration: creatinine clearance (>/= 50 mL/min); hemoglobin >/= 8 g/dL; absolute neutrophils count >/= 1.0 x 10^9/L; platelet count >/= 75 x 10^9/L (without transfusion support); serum bilirubin </= 1.5 x ULN; AST </= 2.5 x ULN (except if liver metastases are present; then AST must be </= 5 x ULN);

7) (Inclusion #6 cont'd) serum creatinine and BUN 1.5 x </= ULN. Serum creatinine must be sampled at least twice within 14 days of receiving the first dose of NPI-0052, with the samples separated by at least 7 days. Both samples must meet entry criteria

8) Signed informed consent

Exclusion Criteria:1) Administration of chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 28 days prior to receipt of study medication (6 weeks for nitrosoureas or mitomycin C; 12 weeks for radioimmunotherapy). Major surgery, other than diagnostic surgery, within 4 weeks before first study drug administration. Radiotherapy within 4 weeks.

2) Patients that require G-CSF and/or platelet support during screening or are likely to require G-CSF and/or platelet support for the duration of the clinical trial.

3) Patients with ongoing coagulopathies and/or taking anticoagulants (warfarin, heparin or low molecular weight heparin) (low dose anticoagulants for IV port maintenance or DVT prophylaxis are permitted).

4) Patients with prior bone marrow transplant therapy (autologous or allogeneic)

5) Patients receiving intrathecal therapy. Patients need to be off IT therapy at least 3 months.

6) Known brain metastases

7) Pre-existing adrenal insufficiency; concomitant therapy with replacement corticosteroids. Pre-existing acute or chronic pancreatitis.

8) Significant cardiac disease defined as: patients with congenital long QT syndrome; congestive heart failure of Class III or IV of the NYHA classification; history of myocardial infarction or active ischemia within 12 months of study enrollment; patients with mean QTcF interval >/= 500 msec identified on three screening ECGs obtained at least 5 minutes apart; interval determination will be based on the analysis performed by central ECG laboratory

9) Patients with a prior hypersensitivity reaction of CTCAE Grade >/= 3 to therapy containing propylene glycol or ethanol

10) Pregnant or breast-feeding women. Female patients must be postmenopausal, surgically sterile or they must agree to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicidal or condom with spermicide, abstinence) for the duration of the study and for one month following study completion. Female patients with child-bearing potential must have a negative serum pregnancy test within the 7 days before the first NPI-0052 administration. Male patients must be surgically sterile or agree to use an acceptable method of contraception.

11) Concurrent, active secondary malignancy for which the patient is receiving therapy. (Lymphoma patients with a diagnosis of a potentially hormone-sensitive tumor who are without evidence of disease for this second malignancy may continue to receive hormonal therapy).

12) Patients with proteinuria >/= Grade 2, untreated urinary tract infection, as well as any pre-exisiting kidney disease (acute or chronic) that would impose excessive risk to the patient.

13) Active uncontrolled bacterial or fungal infection requiring systemic therapy; infection requiring parenteral antibiotics

14) Known to be positive for HIV, Hepatitis A, B, or C.

15) Any medical conditions that, in the investigator's opinion, would impose excessive risk to the patient. Examples of such conditions include infection requiring parenteral or oral anti-infective treatment, any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent.

16) Unwilling or unable to comply with procedures required in this protocol

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Links
Registration Number: NCT00396864
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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