Clinical trial NCT00629473: Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
Official title: A Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Keywords: multiple myeloma
leukemias (inc. CLL)
lymphomas
cutaneous lymphoma
marginal zone lymphoma
advanced malignancies without standard treatment options
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2008-03-06
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 clinical trial examining the safety, pharmacokinetics and pharmacodynamics of escalating doses of the proteasome inhibitor NPI-0052 in patients with advanced malignancies including solid tumors, lymphomas, leukemias and multiple myeloma. By inhibiting proteasomes NPI-0052 prevents the breakdown of proteins involved in signal transduction, which blocks growth and survival in cancer cells.

Detailed description: Patients were enrolled in 1 of 2 study arms. Arm AM (weekly doses of NPI-0052) consisted of patients with solid and hematological malignancies excluding multiple myeloma (MM), and these patients received NPI-0051 once weekly for 3 weeks of every 4 weeks. Arm MM (twice-weekly doses of NPI-0052) consisted of patients with MM and other hematological malignancies, and these patients received NPI-0052 twice weekly for 2 weeks of every 3 weeks. All patients received NPI-0052 administered IV over approximately 1 to 120 minutes. Patients with MM (Arm MM) also received 20 mg dexamethasone per orally or IV on the day before and the day of NPI-0052 dosing.

Patients were initially enrolled in dose-escalating cohorts to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of NPI-0052. Once the RP2D was determined for each arm of the study, the RP2D was evaluated in the dose-expansion stage of the study.

Eligibility criteria: Inclusion Criteria:

* Karnofsky Performance Status (KPS) \> 70%.
* Histologically-confirmed advanced malignancy for which a standard, approved therapy is not available.
* Adequate renal, liver, pancreatic and hematologic function
* Signed informed consent (sample IC form is provided in Appendix A).

Exclusion Criteria

* Administration of chemotherapy, biological, immunotherapy or investigational agent (therapeutic or diagnostic) within 28 days
* Patients that require G-CSF and/or platelet support during screening and are likely to require G-CSF and/or platelet support for the duration of the clinical trial.
* Patients with ongoing coagulopathies and/or taking anticoagulants
* Patients receiving intrathecal therapy.
* Known brain metastases.
* Pre-existing adrenal insufficiency; concomitant therapy with replacement corticosteroids. Pre-existing acute or chronic pancreatitis.
* Significant cardiac disease.
* Pregnant or breast-feeding women.
* 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).
* Patients with proteinuria Grade 2 or greater
* Active uncontrolled bacterial or fungal infection requiring systemic therapy; infection requiring parenteral antibiotics.
* Patients who are known to be HIV positive or have active Hepatitis A, B, or C infection.

Primary outcomes:
measure: Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052
timeFrame: Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)
Secondary outcomes:
measure: To evaluate the pharmacokinetics activity of NPI-0052
timeFrame: Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1
measure: To evaluate the safety and tolerability of NPI-0052
timeFrame: Treatment period through 28-days after the last dose of study drug
measure: To evaluate the pharmacodynamics of NPI-0052
timeFrame: Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycles 1 and 2 and of every other cycle thereafter through study completion
Other outcomes:
Locations:
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancen Center
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Wodonga
country: Australia
facility: Border Medical Oncology
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital and University of Western Australia
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
affiliation: Triphase Research and Development I Corp
name: Steven D Reich, MD
role: STUDY_DIRECTOR
References: