Advanced Cancer
Conditions
Keywords
multiple myeloma, leukemias (inc. CLL), lymphomas, cutaneous lymphoma, marginal zone lymphoma, advanced malignancies without standard treatment options
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.
Interventions
DRUGNPI-0052 on Days 1, 8, 15 every 28 days
NPI-0052 dose ranging from 0.1 to 0.9 mg/m2 NPI-0052 IV injection over 1 to 120 minutes on Days 1, 8, and 15 of 4-week cycles
DRUGNPI-0052 on Days 1, 4, 8, 11 every 21 days
NPI-0052 dose ranging from 0.075 to 0.6 mg/m2 NPI-0052 IV injection over 1 to 120 minutes on Days 1, 4, 8, and 11 of 3-week cycles
DRUGDexamethasone
20 mg oral or IV day before and day after NPI-0052 dosing.
Sponsors
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Australia
Outcome results
None listed