Advanced CancerPhase 1NCT00629473
Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
A Phase 1 study testing NPI-0052 on Days 1, 8, 15 every 28 days, NPI-0052 on Days 1, 4, 8, 11 every 21 days and Dexamethasone in people with Advanced Cancer, run by Celgene at 7 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- NPI-0052 on Days 1, 8, 15 every 28 days, NPI-0052 on Days 1, 4, 8, 11 every 21 days and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 7 sitesAustralia
- Study dates
- Jul 2007to Apr 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Australia7 sites
Peter MacCallum Cancen Center
Melbourne, Victoria, 3002
The Alfred Hospital
Melbourne, Victoria, 3168
Sir Charles Gairdner Hospital and University of Western Australia
Nedlands, Western Australia, 6009
Royal Perth Hospital
Perth, Western Australia, 6001
Mater Adult Hospital
South Brisbane, Queensland, 4101
Border Medical Oncology
Wodonga, Victoria, 3690
The Queen Elizabeth Hospital
Woodville South, South Australia, 5001
About this study
Official title: A Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
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.
Read the 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.
- Conditions
- Advanced Cancer
- Being tested
- NPI-0052 on Days 1, 8, 15 every 28 days, NPI-0052 on Days 1, 4, 8, 11 every 21 days, Dexamethasone
- Keywords
- multiple myeloma, leukemias (inc. CLL), lymphomas, cutaneous lymphoma, marginal zone lymphoma, advanced malignancies without standard treatment options
- Medical subject headings
- Multiple Myeloma, Leukemia, Lymphoma, Lymphoma, T-Cell, Cutaneous, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NPI-0052 on Days 1, 8, 15 every 28 daysDrug
Also called marizomib, proteasome inhibitor
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
NPI-0052 on Days 1, 4, 8, 11 every 21 daysDrug
Also called marizomib, proteasome inhibitor
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
DexamethasoneDrug
Also called Decadron
20 mg oral or IV day before and day after NPI-0052 dosing.
| Study group | Role | What they receive |
|---|---|---|
| Arm AM: advanced malignancies | Experimental | 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 Receives: Drug: NPI-0052 on Days 1, 8, 15 every 28 days |
| Arm MM: multiple myeloma | Experimental | 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. Receives: Drug: NPI-0052 on Days 1, 4, 8, 11 every 21 days; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052
Assess dose-limiting toxicities during Cycle 1 for each treatment arm
Measured: Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)
Secondary outcomes (3)
To evaluate the pharmacokinetics activity of NPI-0052
the assess the time course of NPI-0052 in the body
Measured: Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1
To evaluate the safety and tolerability of NPI-0052
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Measured: Treatment period through 28-days after the last dose of study drug
To evaluate the pharmacodynamics of NPI-0052
proteasome inhibition in blood samples
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2008 (estimated)
- Study startJul 2007
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Steven D Reich, MD, Study director, Triphase Research and Development I Corp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00629473
- Sponsor's protocol ID
- NPI-0052-102
- Status last verified
- Nov 2017
- First submitted
- 26 Feb 2008
- Last updated
- 22 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Clinical Trial of NPI-0052 in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT00629473
- Acronym / sponsor ID
- NPI-0052-102
- Conditions
- Advanced Cancer
- Keywords
- multiple myeloma, leukemias (inc. CLL), lymphomas, cutaneous lymphoma, marginal zone lymphoma, advanced malignancies without standard treatment options
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- Jul 2007
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 6 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm AM: advanced malignancies | Experimental | Drug: NPI-0052 on Days 1, 8, 15 every 28 daysDose 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 | Experimental | Drug: NPI-0052 on Days 1, 4, 8, 11 every 21 days, Drug: DexamethasoneDose 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NPI-0052 on Days 1, 8, 15 every 28 daysAlso: marizomib, proteasome inhibitorNPI-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 | Drug | Arm AM: advanced malignancies |
| NPI-0052 on Days 1, 4, 8, 11 every 21 daysAlso: marizomib, proteasome inhibitorNPI-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 | Drug | Arm MM: multiple myeloma |
| DexamethasoneAlso: Decadron20 mg oral or IV day before and day after NPI-0052 dosing. | Drug | Arm MM: multiple myeloma |
Primary outcome
Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052
Time frame: Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)
Assess dose-limiting toxicities during Cycle 1 for each treatment arm
3 secondary outcomes
To evaluate the pharmacokinetics activity of NPI-0052
Time frame: Baseline, Days 1 and 15 (before injection and 1 hour post injection) of Cycle 1
To evaluate the safety and tolerability of NPI-0052
Time frame: Treatment period through 28-days after the last dose of study drug
To evaluate the pharmacodynamics of NPI-0052
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven D Reich, MD study director
Triphase Research and Development I Corp
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NPI-0052 on Days 1, 8, 15 every 28 days, NPI-0052 on Days 1, 4, 8, 11 every 21 days and Dexamethasone in people with Advanced Cancer, run by Celgene at 7 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NPI-0052 (time frame: Cycle 1 (Arm AM: 28-days, Arm MM: 21-days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2017.