Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00436579
Sorafenib in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing sorafenib tosylate, pharmacological study and assessment of therapy complications in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This randomized phase I trial is studying the side effects, such as high blood pressure, and best dose of sorafenib in treating patients with advanced solid tumors. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- sorafenib tosylate, pharmacological study and assessment of therapy complications
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Sep 2011
- 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 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed malignant solid tumor
- Refractory disease for which curative or palliative measures have failed or for which there is no known superior treatment
- No colorectal cancer or melanoma
- Measurable OR nonmeasurable disease
- Normotensive (blood pressure [BP] ≤ 140/90 mm Hg) meeting 1 of the following criteria:
- No more than 2 attempted measurement sessions for which the documented mean systolic BP is ≤ 140 mm Hg and the diastolic BP is ≤ 90 mm Hg
Show all 61Show fewer
- At least 30 attempted measurement sessions for which the documented mean systolic BP is ≤ 135 mm HG and the diastolic BP is ≤ 85 mm Hg
- Brain metastases allowed provided the following criteria are met:
- Stable neurologic status for ≥ 2 weeks after completion of definitive local therapy (surgery or radiotherapy)
- No neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- ECOG performance status 0-1
- Life expectancy > 12 weeks
- Age ≥ 14 years OR weight ≥ 45 kilograms (pediatric patients)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Hemoglobin ≥ 8.5 g/dL
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN (5 times ULN if there is liver involvement)
- Creatinine ≤ 1.5 times ULN
- No New York Heart Association class II-IV congestive heart failure
- No unstable angina (anginal symptoms at rest) or new-onset angina (began within the past 3 months)
- No myocardial infarction within the past 6 months
- No ventricular arrhythmias requiring anti-arrhythmic therapy
- No thrombotic or embolic events, such as symptomatic pulmonary embolus or any cerebrovascular accident (including transient ischemic attacks) within the past 6 months
- No pulmonary hemorrhage/bleeding event > grade 2 within the past 4 weeks
- No other hemorrhage/bleeding event > grade 3 within the past 4 weeks
- No evidence or history of bleeding diathesis or coagulopathy
- No serious nonhealing wound, ulcer, or bone fracture
- No ongoing or active infection > grade 2
- No psychiatric illness or social situation that would limit compliance with study requirements
- No allergy to sorafenib tosylate or excipients
- No unstable condition that would jeopardize the safety of the patient and/or her/his compliance with the study
- No significant traumatic injury within the past 4 weeks
- No condition that would impair the patient's ability to swallow whole pills or capacity to absorb oral medications
- No seizure disorder requiring steroids or anticonvulsant therapy
- No other concurrent illness
- Recovered from prior therapy
- Prior vascular endothelial growth factor (VEGF) pathway inhibitor (e.g., bevacizumab, sunitinib malate, axitinib) allowed provided the following criteria are met:
- The patient's best response as measured by RECIST criteria was not progressive disease
- If the most recent agent was a small molecule reversible inhibitor (e.g., sunitinib malate, cediranib, or axitinib), the patient must not have taken a dose of the agent within 2 weeks of the baseline blood pressure session and 3 weeks of starting sorafenib tosylate
- If the most recent agent was bevacizumab or VEGF trap the patient must not have received the most recent dose within 5 weeks of the baseline blood pressure session and 6 weeks of starting sorafenib tosylate AND no grade 3 bleeding, cardiovascular, skin, or thyroid toxicities on one of these previous therapies
- More than 2 weeks since prior and no concurrent radiotherapy
- At least 3 weeks since prior and no concurrent chronic epoetin alfa (or congeners)
- More than 3 weeks since prior immunotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- More than 4 weeks since prior major surgery or open biopsy
- At least 3 weeks since prior uncharacterized herbal agents or nutritional supplements
- More than 12 weeks since prior radioimmunotherapy
- No prior sorafenib tosylate
- No prior organ allograft or allogeneic bone marrow or peripheral blood stem cell transplantation
- Patients with a history of autologous transplant and normal bone marrow function are eligible
- No prior cyclosporine, Hypericum perforatum (St. John's wort), or rifampin
- No other concurrent investigational agents
- No other concurrent antineoplastic therapy, including chemotherapy, except androgen-ablating agents (for patients with prior prostate cancer)
- No concurrent hematopoietic growth factors
- No concurrent combination antiretroviral therapy for HIV-positive or chronic hepatitis B-positive patients
- No concurrent hormonal therapy except steroids for adrenal insufficiency or hormones for nondisease-related conditions (e.g., insulin for diabetes)
- Steroids for autoimmune cytopenia allowed provided dose has been stable for 3 weeks
- No anticipated need for other antineoplastic therapy within the next 4 weeks
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Dose Escalation Study of Sorafenib (BAY 43-9006, NSC 724772) in Nomotensive Patients With Advanced Malignancies
This randomized phase I trial is studying the side effects, such as high blood pressure, and best dose of sorafenib in treating patients with advanced solid tumors. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine whether increasing the dose of sorafenib tosylate increases the plasma steady-state concentration in patients with advanced solid tumors.
II. Determine whether increasing the dose of this drug affects blood pressure in these patients.
SECONDARY OBJECTIVES:
- Determine whether the variability in blood pressure elevation is due to pharmacokinetic or pharmacodynamic variability.
II. Compare the toxicity and differences in pharmacokinetics of delivering a higher dose of this drug per day (using two different schedules) vs delivering the currently recommended dose of this drug.
III. Investigate mechanisms of sorafenib tosylate-induced hypophosphatemia with serial measurements of phosphate metabolism (no longer assessed as of 4/29/2009) in these patients, detailed baseline measurements in all patients, and detailed evaluations of patients developing grade 3 or greater hypophosphatemia.
IV. Detect subclinical effects of this drug on measures of thyroid function. V. Identify biomarkers predicting the categorization of patient response.
OUTLINE: This is a randomized, dose-escalation study.
Patients receive oral sorafenib tosylate twice daily on days 1-7 and once on day 8. Patients not experiencing at least one grade 2 or higher toxicity during the initial sorafenib treatment are randomized to 1 of 3 dose-escalated treatment arms.
ARM I: Patients receive higher-dose oral sorafenib tosylate twice daily on days 15-36.
ARM II: Patients receive standard-dose oral sorafenib tosylate three times daily on days 15-36.
ARM III: (closed to accrual as of 4/29/2009) Patients receive standard-dose oral sorafenib tosylate twice daily on days 15-36.
In all arms, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo ambulatory blood pressure monitoring at baseline, on days 7, 14, and 21, and at 6 and 12 months. Blood samples are collected periodically throughout study and evaluated for pharmacokinetic studies, thyroid function, serum markers, and phosphate metabolism*. CT perfusion imaging is performed at baseline, week 6, week 12, and then every 8-12 weeks thereafter.
NOTE: * Phosphate metabolism no longer assessed as of 4/29/2009.
After completion of study treatment, patients are followed every 4 weeks for 1 year and then every 3 months thereafter.
- Being tested
- sorafenib tosylate, pharmacological study, assessment of therapy complications, laboratory biomarker analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenib tosylateDrug
Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar
Given orally
Also called pharmacological studies
assessment of therapy complicationsProcedure or surgery
Ancillary studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (higher-dose enzyme inhibitor therapy) | Experimental | Patients receive higher-dose oral sorafenib tosylate twice daily on days 15-36. Receives: Drug: sorafenib tosylate; Other: pharmacological study; Procedure: assessment of therapy complications; Other: laboratory biomarker analysis |
| Arm II (standard-dose enzyme inhibitor therapy) | Active comparator | Patients receive standard-dose oral sorafenib tosylate three times daily on days 15-36. Receives: Drug: sorafenib tosylate; Other: pharmacological study; Procedure: assessment of therapy complications; Other: laboratory biomarker analysis |
| Arm III (standard-dose enzyme inhibitor therapy) | Active comparator | Patients receive standard-dose oral sorafenib tosylate twice daily on days 15-36. (closed to accrual as of 4/29/2009) Receives: Drug: sorafenib tosylate; Other: pharmacological study; Procedure: assessment of therapy complications; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in BP
BP will first be calculated for each subject as BP after 1 week of treatment minus BP before that treatment dose. Then, for each randomized group separately, the BP changes in the two study phases will be compared using paired t-tests.
Measured: From baseline to day 21
Secondary outcomes (3)
Association between steady state trough levels of sorafenib and BP
Spearman correlation coefficients (since the distribution of sorafenib plasma trough levels is not normal and the relationship may be non-linear) will be calculated and scatter plots will be produced separately for each phase of the study. The association between differences in trough levels at the two different doses and changes in BP due to dose escalation will be tested in a similar manner. comparisons of BP changes and drug plasma levels between the three randomized treatment arms will be analyzed by analysis of variance (ANOVA) followed by Tukey's allowance for multiple comparisons.
Measured: Days 8 and 22
Toxicity rates in the two high dose groups
Toxicity rates will be summarized by type, grade, and attribution and compared using chi-squared tests or Fisher exact tests, as appropriate.
Measured: Every 2 weeks, assessed up to 1 year
Effect of sorafenib dose/exposure on thyroid function
Analysis of variance for repeated measures with one between groups factor (sorafenib dose) and one within subjects factor (time) will be used on serum parathyroid hormone (PTH).
Measured: From baseline up to 50 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2007 (estimated)
- Study startJan 2007
- Primary completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Michael Maitland, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00436579
- Sponsor's protocol ID
- NCI-2009-00221
- Other IDs
- NCI-2009-00221, UCCRC-15002A, CDR0000528261, 15002A, 7768, U01CA069852, P30CA014599
- Status last verified
- Oct 2011
- First submitted
- 15 Feb 2007
- Last updated
- 24 Feb 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Study of Sorafenib (BAY 43-9006, NSC 724772) in Nomotensive Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT00436579
- Acronym / sponsor ID
- NCI-2009-00221
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 110 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2007
- Primary completion
- Sep 2011 (actual)
- First posted
- 19 Feb 2007 (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 randomized phase I trial is studying the side effects, such as high blood pressure, and best dose of sorafenib in treating patients with advanced solid tumors. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Detailed description
PRIMARY OBJECTIVES:
- Determine whether increasing the dose of sorafenib tosylate increases the plasma steady-state concentration in patients with advanced solid tumors.
II. Determine whether increasing the dose of this drug affects blood pressure in these patients.
SECONDARY OBJECTIVES:
- Determine whether the variability in blood pressure elevation is due to pharmacokinetic or pharmacodynamic variability.
II. Compare the toxicity and differences in pharmacokinetics of delivering a higher dose of this drug per day (using two different schedules) vs delivering the currently recommended dose of this drug.
III. Investigate mechanisms of sorafenib tosylate-induced hypophosphatemia with serial measurements of phosphate metabolism (no longer assessed as of 4/29/2009) in these patients, detailed baseline measurements in all patients, and detailed evaluations of patients developing grade 3 or greater hypophosphatemia.
IV. Detect subclinical effects of this drug on measures of thyroid function. V. Identify biomarkers predicting the categorization of patient response.
OUTLINE: This is a randomized, dose-escalation study.
Patients receive oral sorafenib tosylate twice daily on days 1-7 and once on day 8. Patients not experiencing at least one grade 2 or higher toxicity during the initial sorafenib treatment are randomized to 1 of 3 dose-escalated treatment arms.
ARM I: Patients receive higher-dose oral sorafenib tosylate twice daily on days 15-36.
ARM II: Patients receive standard-dose oral sorafenib tosylate three times daily on days 15-36.
ARM III: (closed to accrual as of 4/29/2009) Patients receive standard-dose oral sorafenib tosylate twice daily on days 15-36.
In all arms, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo ambulatory blood pressure monitoring at baseline, on days 7, 14, and 21, and at 6 and 12 months. Blood samples are collected periodically throughout study and evaluated for pharmacokinetic studies, thyroid function, serum markers, and phosphate metabolism*. CT perfusion imaging is performed at baseline, week 6, week 12, and then every 8-12 weeks thereafter.
NOTE: * Phosphate metabolism no longer assessed as of 4/29/2009.
After completion of study treatment, patients are followed every 4 weeks for 1 year and then every 3 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I (higher-dose enzyme inhibitor therapy) | Experimental | Drug: sorafenib tosylate, Other: pharmacological study, Procedure: assessment of therapy complications, Other: laboratory biomarker analysisPatients receive higher-dose oral sorafenib tosylate twice daily on days 15-36. |
| Arm II (standard-dose enzyme inhibitor therapy) | Active comparator | Drug: sorafenib tosylate, Other: pharmacological study, Procedure: assessment of therapy complications, Other: laboratory biomarker analysisPatients receive standard-dose oral sorafenib tosylate three times daily on days 15-36. |
| Arm III (standard-dose enzyme inhibitor therapy) | Active comparator | Drug: sorafenib tosylate, Other: pharmacological study, Procedure: assessment of therapy complications, Other: laboratory biomarker analysisPatients receive standard-dose oral sorafenib tosylate twice daily on days 15-36. (closed to accrual as of 4/29/2009) |
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (61 listed)
- Histologically or cytologically confirmed malignant solid tumor
- Measurable OR nonmeasurable disease
- Normotensive (blood pressure [BP] ≤ 140/90 mm Hg) meeting 1 of the following criteria:
- Brain metastases allowed provided the following criteria are met:
- ECOG performance status 0-1
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 |
|---|---|---|
| sorafenib tosylateAlso: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, NexavarGiven orally | Drug | Arm I (higher-dose enzyme inhibitor therapy), Arm II (standard-dose enzyme inhibitor therapy), Arm III (standard-dose enzyme inhibitor therapy) |
| pharmacological studyAlso: pharmacological studies | Other | Arm I (higher-dose enzyme inhibitor therapy), Arm II (standard-dose enzyme inhibitor therapy), Arm III (standard-dose enzyme inhibitor therapy) |
| assessment of therapy complicationsAncillary studies | Procedure or surgery | Arm I (higher-dose enzyme inhibitor therapy), Arm II (standard-dose enzyme inhibitor therapy), Arm III (standard-dose enzyme inhibitor therapy) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (higher-dose enzyme inhibitor therapy), Arm II (standard-dose enzyme inhibitor therapy), Arm III (standard-dose enzyme inhibitor therapy) |
Primary outcome
Changes in BP
Time frame: From baseline to day 21
BP will first be calculated for each subject as BP after 1 week of treatment minus BP before that treatment dose. Then, for each randomized group separately, the BP changes in the two study phases will be compared using paired t-tests.
3 secondary outcomes
Association between steady state trough levels of sorafenib and BP
Time frame: Days 8 and 22
Toxicity rates in the two high dose groups
Time frame: Every 2 weeks, assessed up to 1 year
Effect of sorafenib dose/exposure on thyroid function
Time frame: From baseline up to 50 days
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 24 Feb 2014.
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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.
Michael Maitland principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sorafenib tosylate, pharmacological study and assessment of therapy complications in people with Unspecified Adult Solid Tumor, Protocol Specific, 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 61 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 24 Feb 2014. 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 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 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?
Changes in BP (time frame: From baseline to day 21). 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 24 Feb 2014; AzTrials last refreshed its copy on 30 Oct 2026.