LymphomaPhase 1NCT00215605
Study of XL184 (Cabozantinib) in Adults With Advanced Malignancies
A Phase 1 study testing XL184 in people with Lymphoma and Cancer, run by Exelixis at 5 sites in United States.
Trial summary
The purpose of this study is to determine the best and safest dose of XL184 administered orally. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration. To determine the highest safe dose, subjects will receive different amounts of the drug. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Cancer, Thyroid Carcinoma
- What is being tested?
- XL184
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 5 sitesUnited States
- Study dates
- Sep 2005to Jul 2012
- 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
- Histologically confirmed advanced malignancy (solid tumor or lymphoma) that is metastatic or unresectable for which standard curative measures do not exist or are no longer effective
- Eastern Cooperative Oncology Group (ECOG) performance status </= 2
- Life expectancy greater than 3 months
- Adequate organ and marrow function
- Written informed consent
- Use of acceptable methods of contraception during the course of the study and for 3 months after completion of study
- In the MTD expanded cohort: at least 20 subjects with metastatic and/or advanced/locally recurrent Medullary Thyroid Cancer not appropriate for surgical resection with measurable disease as defined by RECIST
Who cannot join
- Chemotherapy, immunotherapy or radiation within 4 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first scheduled dose of XL184
- Administration of an investigational drug within 30 days of the first dose of XL184
- Subject has not recovered from adverse events due to investigational agents or other medications administered more than 4 weeks before study enrollment
- Known brain metastases
- Uncontrolled intercurrent illness
- Pregnancy or breastfeeding
- Known HIV positive
- Known allergy or hypersensitivity to any of the components of the XL184 formulation
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Johns Hopkins University
Baltimore, Maryland, 21231
University of Chicago
Chicago, Illinois, 60637
Univ. of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
Official title: A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL184 Administered Orally to Subjects With Advanced Malignancies
The purpose of this study is to determine the best and safest dose of XL184 administered orally. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration. To determine the highest safe dose, subjects will receive different amounts of the drug. The first group of subjects will receive the lowest dose of XL184. As long as no medically unacceptable side effects are noted, the dose will be increased for the next group. When the maximum tolerated dose (MTD) is reached, at least 20 subjects with Medullary Thyroid Cancer (MTC) will be enrolled to evaluate the effect of XL184 in this population.
- Conditions
- Lymphoma, Cancer, Thyroid Carcinoma
- Being tested
- XL184
- Keywords
- Advanced Malignancies, Solid Tumor, Medullary Thyroid Cancer
- Medical subject headings
- Lymphoma, Neoplasms, Thyroid Neoplasms, Carcinoma, Medullary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XL184Drug
Flavored liquid suspension or gelatin capsules supplied in 25-mg and 100-mg strengths; daily dosing or intermittent schedule (daily dosing followed by dosing holiday in cycles)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: XL184 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity of oral administration of XL184
Measured: Assessed during periodic visits
Evaluate plasma pharmacokinetics and estimate renal elimination of oral administration of XL184
Measured: Assessed during periodic visits
Secondary outcomes (3)
Long-term safety/tolerability of XL184 after oral administration for up to 1 year
Measured: Assessed during periodic visits
Evaluate preliminary tumor response after repeated XL184 administration
Measured: Assessed during periodic visits
In MTD expanded cohort: Progression-free survival and duration of response in subjects with advanced or recurrent medullary thyroid cancer
Measured: Assessed during periodic visits
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startSep 2005
- Primary completionApr 2011
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by ExelixisThe 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
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Exelixis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00215605
- Sponsor's protocol ID
- XL184-001
- Status last verified
- Feb 2013
- First submitted
- 20 Sep 2005
- Last updated
- 27 Feb 2013
- Results posted
- No
Publications
Kurzrock R, Atkins J, Wheler J, Fu S, Naing A, Busaidy N, Hong D, Sherman S. Tumor marker and measurement fluctuations may not reflect treatment efficacy in patients with medullary thyroid carcinoma on long-term RET inhibitor therapy. Ann Oncol. 2013 Sep;24(9):2256-61. doi: 10.1093/annonc/mdt177. Epub 2013 May 14.
PubMed 23676418Kim KB, Cabanillas ME, Lazar AJ, Williams MD, Sanders DL, Ilagan JL, Nolop K, Lee RJ, Sherman SI. Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation. Thyroid. 2013 Oct;23(10):1277-83. doi: 10.1089/thy.2013.0057. Epub 2013 Jul 17.
PubMed 23489023Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23.
PubMed 21606412
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL184 Administered Orally to Subjects With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT00215605
- Acronym / sponsor ID
- XL184-001
- Conditions
- Lymphoma, Cancer, Thyroid Carcinoma
- Keywords
- Advanced Malignancies, Solid Tumor, Medullary Thyroid Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- ExelixisIndustry (pharma, biotech, devices)
- Study start
- Sep 2005
- Primary completion
- Apr 2011 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 22 Sep 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.
The purpose of this study is to determine the best and safest dose of XL184 administered orally. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration. To determine the highest safe dose, subjects will receive different amounts of the drug. The first group of subjects will receive the lowest dose of XL184. As long as no medically unacceptable side effects are noted, the dose will be increased for the next group. When the maximum tolerated dose (MTD) is reached, at least 20 subjects with Medullary Thyroid Cancer (MTC) will be enrolled to evaluate the effect of XL184 in this population.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: XL184 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically confirmed advanced malignancy (solid tumor or lymphoma) that is metastatic or unresectable for which standard curative measures do not exist or are no longer effective
- Eastern Cooperative Oncology Group (ECOG) performance status </= 2
- Life expectancy greater than 3 months
- Adequate organ and marrow function
- Written informed consent
Key exclusion criteria (8 listed)
- Chemotherapy, immunotherapy or radiation within 4 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first scheduled dose of XL184
- Administration of an investigational drug within 30 days of the first dose of XL184
- Subject has not recovered from adverse events due to investigational agents or other medications administered more than 4 weeks before study enrollment
- Known brain metastases
- Uncontrolled intercurrent illness
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 |
|---|---|---|
| XL184Flavored liquid suspension or gelatin capsules supplied in 25-mg and 100-mg strengths; daily dosing or intermittent schedule (daily dosing followed by dosing holiday in cycles) | Drug | 1 |
Primary outcome
Safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity of oral administration of XL184
Time frame: Assessed during periodic visits
Evaluate plasma pharmacokinetics and estimate renal elimination of oral administration of XL184
Time frame: Assessed during periodic visits
3 secondary outcomes
Long-term safety/tolerability of XL184 after oral administration for up to 1 year
Time frame: Assessed during periodic visits
Evaluate preliminary tumor response after repeated XL184 administration
Time frame: Assessed during periodic visits
In MTD expanded cohort: Progression-free survival and duration of response in subjects with advanced or recurrent medullary thyroid cancer
Time frame: Assessed during periodic visits
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 27 Feb 2013.
- Derived from this study: PubMed 23676418Kurzrock R, Atkins J, Wheler J, Fu S, Naing A, Busaidy N, Hong D, Sherman S. Tumor marker and measurement fluctuations may not reflect treatment efficacy in patients with medullary thyroid carcinoma on long-term RET inhibitor therapy. Ann Oncol. 2013 Sep;24(9):2256-61. doi: 10.1093/annonc/mdt177. Epub 2013 May 14.
- Derived from this study: PubMed 23489023Kim KB, Cabanillas ME, Lazar AJ, Williams MD, Sanders DL, Ilagan JL, Nolop K, Lee RJ, Sherman SI. Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation. Thyroid. 2013 Oct;23(10):1277-83. doi: 10.1089/thy.2013.0057. Epub 2013 Jul 17.
- Derived from this study: PubMed 21606412Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23.
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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.
The record lists no contact. Use the official record to reach the sponsor.
5 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 XL184 in people with Lymphoma and Cancer, run by Exelixis at 5 sites 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 7 inclusion and 8 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 27 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 5 sites 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, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity of oral administration of XL184 (time frame: Assessed during periodic visits). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00215605, which also lists 3 linked publications.
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 27 Feb 2013.