Refractory Multiple MyelomaPhase 1/2NCT00243035
Tipifarnib and Bortezomib in Treating Patients With Relapsed Multiple Myeloma
A Phase 1/2 study testing bortezomib, tipifarnib and laboratory biomarker analysis in people with Refractory Multiple Myeloma and Stage II Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I/II trial is studying the side effects and best dose of tipifarnib when given together with bortezomib and to see how well they work in treating patients with relapsed multiple myeloma. Tipifarnib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma
- What is being tested?
- bortezomib, tipifarnib and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to Feb 2007
- Phase
- Phase 1/2
- 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
- Diagnosis of multiple myeloma
- Stage II or III disease
- Relapsed disease after ≥ 2 prior therapies*, confirmed by the presence of 1 of the following:
- New lytic lesion
- A 25% increase in urine or serum monoclonal protein
- Patients who received prior bortezomib must have responded to therapy
Show all 51Show fewer
- Measurable disease, defined by 1 or more of the following criteria:
- Serum M-component ≥ 1.0 g/dL by serum protein electrophoresis
- Urine M-protein excretion > 200 mg per 24-hour collection, by urine protein electrophoresis
- Performance status - Karnofsky 60-100%
- More than 8 weeks
- Platelet count ≥ 100,000/mm^3
- Absolute neutrophil count ≥ 1,000/mm^3
- Bilirubin ≤ 2 mg/dL
- Direct bilirubin ≤ 2 times upper limit of normal (ULN)
- AST or ALT ≤ 2 times ULN
- Creatinine ≤ 1.5 times ULN
- Calcium ≤ 12 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to swallow study medication
- Capable of following directions regarding study medication, or has a daily caregiver who will be responsible for administering study medication
- No peripheral neuropathy ≥ grade 2
- No hypersensitivity to any of the following:
- Bortezomib
- Boron
- Mannitol
- Imidazole compounds (e.g., clotrimazole, ketoconazole, miconazole, econazole)
- No serious medical or psychiatric illness that would preclude study compliance
- No other life-threatening illness (unrelated to tumor)
- No other active or invasive malignancy within the past 3 years except for nonmelanoma skin cancer
- No serious infection
- No prior allogeneic bone marrow transplantation
- More than 30 days since prior and no concurrent immunotherapy
- More than 30 days since prior and no concurrent cytotoxic chemotherapy
- More than 14 days since prior high-dose corticosteroids
- No concurrent therapeutic corticosteroids (e.g., > 10 mg prednisone per day)
- No concurrent hormonal therapy
- No concurrent antiemetic corticosteroids
- More than 14 days since prior and no concurrent radiotherapy
- More than 1 year since prior bortezomib
- More than 14 days since prior investigational drugs
- No prior tipifarnib
- No other concurrent cancer-related treatment
- No concurrent administration of the following enzyme-inducing anti-epileptic drugs:
- Phenytoin
- Phenobarbital
- Carbamazepine
- No concurrent magnesium- or aluminum-based antacids within 2 hours before or after tipifarnib administration
- Concurrent pamidronate or other bisphosphonates allowed
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Dose Escalation Study of R115777 (Zarnestra) Combined With Velcade® (PS-341) in Patients With Relapsed Multiple Myeloma.
This phase I/II trial is studying the side effects and best dose of tipifarnib when given together with bortezomib and to see how well they work in treating patients with relapsed multiple myeloma. Tipifarnib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving tipifarnib together with bortezomib may kill more cancer cells.
Read the detailed description
OBJECTIVES: Primary I. Determine the maximum tolerated dose and dose-limiting toxicity of tipifarnib when administered with bortezomib in patients with relapsed multiple myeloma. (Phase I) II. Determine the response rate in patients treated with this regimen. (Phase II) III. Determine the toxicity profile of this regimen in these patients. (Phase II)
Secondary I. Determine the progression-free survival of patients treated with this regimen. (Phase II)
Tertiary I. Determine whether this regimen overcomes CAM-DR in primary myeloma cells and establish whether ex vivo efficacy predicts a clinical response in these patients.
II. Determine if activated Akt predicts clinical resistance and if levels of phosphorylated Akt are reduced by tipifarnib and bortezomib in these patients.
III. Determine whether molecular profiles from primary isolates (suspension vs adhered) correlate with clinical response in patients treated with this regimen.
OUTLINE: This is a phase I dose-escalation study of tipifarnib followed by a phase II study.
Phase I: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.
Phase II: Patients receive bortezomib as in phase I and tipifarnib as in phase I at the MTD.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: Approximately 52-64 patients will be accrued for this study.
- Being tested
- bortezomib, tipifarnib, laboratory biomarker analysis
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Given IV
tipifarnibDrug
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bortezomib, tipifarnib) | Experimental | Phase I: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.
Phase II: Patients receive bortezomib as in phase I and tipifarnib as in phase I at the MTD. Receives: Drug: bortezomib; Drug: tipifarnib; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of tipifarnib as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 (phase I)
Measured: Up to day 21
Response rate (complete response [CR] + partial response [PR]) determined using the Bladé Response criteria (phase II)
Exact 95% confidence intervals constructed.
Measured: Up to 6 weeks
Toxicities, graded according to the NCI CTCAE v3.0 (phase II)
Measured: Up to 2 years
Secondary outcomes (9)
Proportion of patients overcoming CAM-DR
An exact 95% confidence interval for that proportion will be computed.
Measured: Prior to therapy
Proportion of patients overcoming CAM-DR
An exact 95% confidence interval for that proportion will be computed.
Measured: Day 11 of course 1
Relationship of overcoming CAM-DR and clinical response
Compared using a chi-square contingency table test at the two-sided 0.05 significance level.
Measured: Prior to therapy
Relationship of overcoming CAM-DR and clinical response
Compared using a chi-square contingency table test at the two-sided 0.05 significance level.
Measured: Day 11 of course 1
Clinical resistance and levels of phosphorylated Akt
P-Akt levels both pre and post treatment will be obtained and compared using a paired t test. Logistic regression will be used with P-Akt activity as independent variable in a logistic regression modeling probability of response. Odds ratio indicating change in odds of response associated with a unit change in P-Akt level will be computed as well as a 95% confidence interval for that odds ratio.
Measured: Prior to therapy
Clinical resistance and levels of phosphorylated Akt
P-Akt levels both pre and post treatment will be obtained and compared using a paired t test. Logistic regression will be used with P-Akt activity as independent variable in a logistic regression modeling probability of response. Odds ratio indicating change in odds of response associated with a unit change in P-Akt level will be computed as well as a 95% confidence interval for that odds ratio.
Measured: Day 11 of course 1
Correlation of molecular profiles from primary isolates with clinical response
Compared using paired t tests at the 0.05 significance level.
Measured: Prior to therapy
Correlation of molecular profiles from primary isolates with clinical response
Compared using paired t tests at the 0.05 significance level.
Measured: Day 11 of course 1
Progression-free survival (phase II)
Summarized with Kaplan-Meier curve and related statistics.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2005 (estimated)
- Study startAug 2005
- Primary completionFeb 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Darrin Beaupre, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00243035
- Sponsor's protocol ID
- NCI-2012-02675
- Other IDs
- NCI-2012-02675, MCC-VEL-04-111, CDR0000446083, NCI-7032, VEL-04-111, 7032, R01CA083978
- Status last verified
- Oct 2013
- First submitted
- 20 Oct 2005
- Last updated
- 8 Oct 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Study of R115777 (Zarnestra) Combined With Velcade® (PS-341) in Patients With Relapsed Multiple Myeloma.
- ClinicalTrials.gov ID
- NCT00243035
- Acronym / sponsor ID
- NCI-2012-02675
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 2005
- Primary completion
- Feb 2007 (actual)
- First posted
- 21 Oct 2005 (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 phase I/II trial is studying the side effects and best dose of tipifarnib when given together with bortezomib and to see how well they work in treating patients with relapsed multiple myeloma. Tipifarnib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving tipifarnib together with bortezomib may kill more cancer cells.
Detailed description
OBJECTIVES: Primary I. Determine the maximum tolerated dose and dose-limiting toxicity of tipifarnib when administered with bortezomib in patients with relapsed multiple myeloma. (Phase I) II. Determine the response rate in patients treated with this regimen. (Phase II) III. Determine the toxicity profile of this regimen in these patients. (Phase II)
Secondary I. Determine the progression-free survival of patients treated with this regimen. (Phase II)
Tertiary I. Determine whether this regimen overcomes CAM-DR in primary myeloma cells and establish whether ex vivo efficacy predicts a clinical response in these patients.
II. Determine if activated Akt predicts clinical resistance and if levels of phosphorylated Akt are reduced by tipifarnib and bortezomib in these patients.
III. Determine whether molecular profiles from primary isolates (suspension vs adhered) correlate with clinical response in patients treated with this regimen.
OUTLINE: This is a phase I dose-escalation study of tipifarnib followed by a phase II study.
Phase I: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.
Phase II: Patients receive bortezomib as in phase I and tipifarnib as in phase I at the MTD.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: Approximately 52-64 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (bortezomib, tipifarnib) | Experimental | Drug: bortezomib, Drug: tipifarnib, Other: laboratory biomarker analysisPhase I: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tipifarnib until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD. Phase II: Patients receive bortezomib as in phase I and tipifarnib as in phase I at the MTD. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (51 listed)
- Diagnosis of multiple myeloma
- Relapsed disease after ≥ 2 prior therapies*, confirmed by the presence of 1 of the following:
- Patients who received prior bortezomib must have responded to therapy
- Measurable disease, defined by 1 or more of the following criteria:
- Performance status - Karnofsky 60-100%
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| bortezomibGiven IV | Drug | Treatment (bortezomib, tipifarnib) |
| tipifarnibGiven orally | Drug | Treatment (bortezomib, tipifarnib) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (bortezomib, tipifarnib) |
Primary outcome
Maximum tolerated dose of tipifarnib as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 (phase I)
Time frame: Up to day 21
Response rate (complete response [CR] + partial response [PR]) determined using the Bladé Response criteria (phase II)
Time frame: Up to 6 weeks
Exact 95% confidence intervals constructed.
Toxicities, graded according to the NCI CTCAE v3.0 (phase II)
Time frame: Up to 2 years
9 secondary outcomes
Proportion of patients overcoming CAM-DR
Time frame: Prior to therapy
Proportion of patients overcoming CAM-DR
Time frame: Day 11 of course 1
Relationship of overcoming CAM-DR and clinical response
Time frame: Prior to therapy
Relationship of overcoming CAM-DR and clinical response
Time frame: Day 11 of course 1
Clinical resistance and levels of phosphorylated Akt
Time frame: Prior to therapy
Clinical resistance and levels of phosphorylated Akt
Time frame: Day 11 of course 1
Correlation of molecular profiles from primary isolates with clinical response
Time frame: Prior to therapy
Correlation of molecular profiles from primary isolates with clinical response
Time frame: Day 11 of course 1
Progression-free survival (phase II)
Time frame: Up to 2 years
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2013.
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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.
Darrin Beaupre principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing bortezomib, tipifarnib and laboratory biomarker analysis in people with Refractory Multiple Myeloma and Stage II Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.
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 51 inclusion and 0 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: stopped early, as of the sponsor's last update on 8 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early. Results are not available in the source record.
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?
Maximum tolerated dose of tipifarnib as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 (phase I) (time frame: Up to day 21). The study lists 3 primary outcomes in all. 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 8 Oct 2013.