Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
- Conditions
- Advanced Cancer
- Interventions
- Drug: NPI-0052 on Days 1, 4, 8, 11 every 21 daysDrug: NPI-0052 on Days 1, 8, 15 every 28 days
- Registration Number
- NCT00629473
- Lead Sponsor
- Celgene
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 86
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm MM: multiple myeloma NPI-0052 on Days 1, 4, 8, 11 every 21 days Dose Escalation - 8 dose cohorts NPI-0052 on Days 1, 4, 8, 11 every 21 days NPI-0052 doses ranging from 0.075 to 0.6 mg/m2 Dexamethasone 20 mg oral or IV day before and day after NPI-0052 dosing. Arm AM: advanced malignancies NPI-0052 on Days 1, 8, 15 every 28 days Dose Escalation - 9 dose cohorts NPI-0052 on Days 1, 8, 15 every 28 days NPI-0052 doses ranging from 0.1 to 0.9 mg/m2 Arm MM: multiple myeloma Dexamethasone Dose Escalation - 8 dose cohorts NPI-0052 on Days 1, 4, 8, 11 every 21 days NPI-0052 doses ranging from 0.075 to 0.6 mg/m2 Dexamethasone 20 mg oral or IV day before and day after NPI-0052 dosing.
- Primary Outcome Measures
Name Time Method Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052 Cycle 1 (Arm AM: 28-days, Arm MM: 21-days) Assess dose-limiting toxicities during Cycle 1 for each treatment arm
- Secondary Outcome Measures
Name Time Method To evaluate the pharmacokinetics activity of NPI-0052 Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1 the assess the time course of NPI-0052 in the body
To evaluate the safety and tolerability of NPI-0052 Treatment period through 28-days after the last dose of study drug Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\]
To evaluate the pharmacodynamics of NPI-0052 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 proteasome inhibition in blood samples
Trial Locations
- Locations (7)
Mater Adult Hospital
🇦🇺South Brisbane, Queensland, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Sir Charles Gairdner Hospital and University of Western Australia
🇦🇺Nedlands, Western Australia, Australia
Peter MacCallum Cancen Center
🇦🇺Melbourne, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Border Medical Oncology
🇦🇺Wodonga, Victoria, Australia