Refractory MalignancyPhase 1NCT00613145
Study of the Pharmacokinetics/Safety of Sorafenib + Capecitabine in Advanced Solid Tumors
A Phase 1 study testing Capecitabine and Sorafenib in people with Refractory Malignancy, run by SCRI Development Innovations, LLC at 1 site in United States.
Trial summary
This is a phase I, randomized, safety and pharmacokinetic (PK) study of sorafenib given in combination with capecitabine. The study will enroll two simultaneous cohorts; patients will be randomly assigned to either Cohort A or Cohort B. A third cohort (C) may be added to the protocol at a later date. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Malignancy
- What is being tested?
- Capecitabine and Sorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to May 2010
- 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
- Patients with advanced solid tumor malignancy for whom no effective therapy exists or who have failed effective therapy. Exceptions are patients with advanced solid malignancies where either capecitabine or sorafenib has been approved as initial chemotherapy either alone or in combination.
- A maximum of 4 prior cytotoxic chemotherapy regimens in the metastatic setting.
- Patients previously treated with capecitabine or infusional 5-FU are eligible, but must not have been a part of the immediately prior regimen, or received the treatment within 3 months prior to study initiation.
- Patients who have received prior radiation therapy are eligible, provided that this is not the only site of evaluable disease. Prior therapy must have been completed > 3 weeks before study enrollment.
- An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.
- Life expectancy of > 3 months.
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- Adequate bone marrow, liver, and renal function as assessed by the following:
- Hemoglobin ≥ 9.0 g/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal range (ULN) (unless liver metastases are present, then ≤ 5 × ULN is allowed)
- Total bilirubin ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN
- ANC ≥ 1.5 × 109/L
- Platelets ≥ 100 × 109/L
- International Normalized Ratio for prothrombin time (PT-INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) within normal limits
- Patients must be able to swallow and retain oral medications.
- Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedure to grade ≤ 1 per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
- Patients with a history of brain metastasis treated with radiation and/or surgery ≥ 8 weeks prior to study enrollment are eligible for the study if the effects of that treatment have resolved. These patients must have a post-treatment magnetic resonance imaging (MRI) of the brain within 8 weeks of study entry that shows no new brain metastasis and no further progression of prior lesions.
- Patients with deep vein thrombosis/pulmonary embolism (DVT/PE) are allowed if they have been on anti-coagulation for > 3 months, and they are on a stable dose of coumadin with 2 serial documented individual normalized ratios (INRs) in the therapeutic range at least 72 hours apart.
- Women of childbearing potential and men with partners of childbearing potential must agree to use a method of contraception that is acceptable to their physicians from time of first signing the informed consent until at least 12 weeks after the end of study drug administration. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
- Ability to understand and willingness to sign a written informed consent document.
- Willingness and ability to comply with scheduled visits, treatment arrangements, laboratory tests, and other study procedures.
Who cannot join
- Known untreated brain metastasis.
- Prior irradiation to > 25% of the bone marrow (whole pelvis = 25%).
- Any previous major surgery within 4 weeks of the start of the study, or within 1 week of any minor surgical procedure (e.g., dental work, port placement, etc.).
- Treatment with chemotherapy or an investigational new drug within 28 days of day 1 of treatment.
- No prior anti-vascular endothelial growth factor (VEGF) therapy (with the exception of bevacizumab if the last dose was > 3 months prior to study treatment), including VEGF receptor inhibitors, thalidomide or thalidomide-like therapy, or any other (including investigational) anti-angiogenic treatment of any kind. Only prior bevacizumab is allowed.
- Patients with any serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
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- Evidence or history of bleeding diathesis or coagulopathy.
- Any serious non-healing wound, ulcer, or bone fracture.
- Cardiac disease, including: congestive heart failure (CHF) > Class II per New York Heart Association (NYHA) classification (see Appendix B); unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension (i.e., systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg despite optimal medical management).
- Psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- Patients with a history of DVT/PE are not allowed if the thrombosis occurred within the last 6 months.
- Pulmonary hemorrhage or bleeding event > grade 2 within 4 weeks of study randomization.
- Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of study randomization.
- Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
- Known or suspected allergy to sorafenib, or hypersensitivity to capecitabine or any of the components of fluorouracil.
- History of severe and unexpected reactions to fluoropyrimidine therapy, or patients with dihydropyrimidine dehydrogenase deficiency.
- Concomitant use of St. John's Wort or rifampin (rifampicin).
- Women who are pregnant or breastfeeding.
- Any condition that impairs patient's ability to swallow whole pills.
- Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's Disease, ulcerative colitis).
Trial locations and contacts
1 site in 1 country.
United States1 site
Tennessee Oncology, PLLC
Nashville, Tennessee, 37023
About this study
Official title: A Phase I Pharmacokinetic and Safety Study of Sorafenib + Capecitabine in Advanced Solid Tumors
This is a phase I, randomized, safety and pharmacokinetic (PK) study of sorafenib given in combination with capecitabine. The study will enroll two simultaneous cohorts; patients will be randomly assigned to either Cohort A or Cohort B. A third cohort (C) may be added to the protocol at a later date.
Read the detailed description
During Cycle 1, patients will receive capecitabine alone for the first 7 days (Cohort A will receive 750 mg/m2 of capecitabine twice daily, and Cohort B will receive 1000 mg/m2 of capecitabine twice daily for the first 7 days of Cycle 1). For days 8-14 of Cycle 1, patients will receive capecitabine (750 mg/m2 twice daily for Cohort A; 1000 mg/m2 twice daily for Cohort B) combined with sorafenib (400 mg twice daily for both cohorts); on days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily for both cohorts). Beginning with day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows: Cohort A will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 750 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle.
Cohort B will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 1000 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle. After 6 patients each are enrolled into Cohort A and Cohort B, one of these two cohorts will enroll an additional 6-12 patients in an expansion phase.
- Conditions
- Refractory Malignancy
- Being tested
- Capecitabine and Sorafenib
- Keywords
- Refractory Malignancy, Phase I, Sorafenib, Capecitabine
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Capecitabine and SorafenibDrug
Also called Xeloda, Nexavar
During Cycle 1, patients will receive capecitabine alone for the first 7 days (Cohort A will receive 750 mg/m2 of capecitabine twice daily). For Days 8-14 of Cycle 1, patients will receive capecitabine (750 mg/m2 twice daily for Cohort A) combined with sorafenib (400 mg twice daily); on Days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily). Beginning with Day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows:
Cohort A will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 750 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle.
Capecitabine and SorafenibDrug
Also called Xeloda, Nexavar
During Cycle 1, patients will receive capecitabine alone for the first 7 days Cohort B will receive 1000 mg/m2 of capecitabine twice daily for the first 7 days of Cycle 1). For Days 8-14 of Cycle 1, patients will receive capecitabine (1000 mg/m2 twice daily for Cohort B) combined with sorafenib (400 mg twice daily for both cohorts); on Days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily). Beginning with Day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows: Cohort B will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 1000 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Treatment with Capecitabine and Sorafenib Receives: Drug: Capecitabine and Sorafenib |
| B | Active comparator | Treatment with Capecitabine and Sorafenib Receives: Drug: Capecitabine and Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of the combination therapy
Measured: 18 Months
Secondary outcomes (1)
Evaluation of antitumor activity of the combination therapy
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionMay 2009
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory MalignancyStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Jeffrey Infante, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00613145
- Sponsor's protocol ID
- SCRI REFMAL 122
- Status last verified
- Jan 2013
- First submitted
- 17 Jan 2008
- Last updated
- 4 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Pharmacokinetic and Safety Study of Sorafenib + Capecitabine in Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00613145
- Acronym / sponsor ID
- SCRI REFMAL 122
- Conditions
- Refractory Malignancy
- Keywords
- Refractory Malignancy, Phase I, Sorafenib, Capecitabine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Feb 2008
- Primary completion
- May 2009 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 12 Feb 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 I, randomized, safety and pharmacokinetic (PK) study of sorafenib given in combination with capecitabine. The study will enroll two simultaneous cohorts; patients will be randomly assigned to either Cohort A or Cohort B. A third cohort (C) may be added to the protocol at a later date.
Detailed description
During Cycle 1, patients will receive capecitabine alone for the first 7 days (Cohort A will receive 750 mg/m2 of capecitabine twice daily, and Cohort B will receive 1000 mg/m2 of capecitabine twice daily for the first 7 days of Cycle 1). For days 8-14 of Cycle 1, patients will receive capecitabine (750 mg/m2 twice daily for Cohort A; 1000 mg/m2 twice daily for Cohort B) combined with sorafenib (400 mg twice daily for both cohorts); on days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily for both cohorts). Beginning with day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows: Cohort A will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 750 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle.
Cohort B will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 1000 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle. After 6 patients each are enrolled into Cohort A and Cohort B, one of these two cohorts will enroll an additional 6-12 patients in an expansion phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: Capecitabine and SorafenibTreatment with Capecitabine and Sorafenib |
| B | Active comparator | Drug: Capecitabine and SorafenibTreatment with Capecitabine and Sorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients with advanced solid tumor malignancy for whom no effective therapy exists or who have failed effective therapy. Exceptions are patients with advanced solid malignancies where either capecitabine or sorafenib has been approved as initial chemotherapy either alone or in combination.
- A maximum of 4 prior cytotoxic chemotherapy regimens in the metastatic setting.
- Patients previously treated with capecitabine or infusional 5-FU are eligible, but must not have been a part of the immediately prior regimen, or received the treatment within 3 months prior to study initiation.
- Patients who have received prior radiation therapy are eligible, provided that this is not the only site of evaluable disease. Prior therapy must have been completed > 3 weeks before study enrollment.
- An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.
Key exclusion criteria (22 listed)
- Known untreated brain metastasis.
- Prior irradiation to > 25% of the bone marrow (whole pelvis = 25%).
- Any previous major surgery within 4 weeks of the start of the study, or within 1 week of any minor surgical procedure (e.g., dental work, port placement, etc.).
- Treatment with chemotherapy or an investigational new drug within 28 days of day 1 of treatment.
- No prior anti-vascular endothelial growth factor (VEGF) therapy (with the exception of bevacizumab if the last dose was > 3 months prior to study treatment), including VEGF receptor inhibitors, thalidomide or thalidomide-like therapy, or any other (including investigational) anti-angiogenic treatment of any kind. Only prior bevacizumab is allowed.
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 |
|---|---|---|
| Capecitabine and SorafenibAlso: Xeloda, NexavarDuring Cycle 1, patients will receive capecitabine alone for the first 7 days (Cohort A will receive 750 mg/m2 of capecitabine twice daily). For Days 8-14 of Cycle 1, patients will receive capecitabine (750 mg/m2 twice daily for Cohort A) combined with sorafenib (400 mg twice daily); on Days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily). Beginning with Day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows: Cohort A will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 750 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle. | Drug | A |
| Capecitabine and SorafenibAlso: Xeloda, NexavarDuring Cycle 1, patients will receive capecitabine alone for the first 7 days Cohort B will receive 1000 mg/m2 of capecitabine twice daily for the first 7 days of Cycle 1). For Days 8-14 of Cycle 1, patients will receive capecitabine (1000 mg/m2 twice daily for Cohort B) combined with sorafenib (400 mg twice daily for both cohorts); on Days 15-21 of Cycle 1, patients will receive sorafenib alone (400 mg twice daily). Beginning with Day 1 of Cycle 2 and all treatment cycles thereafter, patients will be dosed as follows: Cohort B will receive sorafenib orally at 400 mg twice daily for 21 days, and capecitabine orally at 1000 mg/m2 twice daily for the first 14 days of a 21-day treatment cycle. | Drug | B |
Primary outcome
Safety and tolerability of the combination therapy
Time frame: 18 Months
1 secondary outcome
Evaluation of antitumor activity of the combination therapy
Time frame: 18 months
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 4 Feb 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.
Jeffrey Infante, M.D. study chair
SCRI Development Innovations, LLC
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 Capecitabine and Sorafenib in people with Refractory Malignancy, run by SCRI Development Innovations, LLC 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 21 inclusion and 22 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 4 Feb 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 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?
Safety and tolerability of the combination therapy (time frame: 18 Months). 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 4 Feb 2013.