Solid TumorsPhase 1NCT00984425
The Treatment of Lapatinib in Combination With Sorafenib in Patients With Advanced Refractory Solid Tumors
A Phase 1 study testing Lapatinib and Sorafenib in people with Solid Tumors, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
Over the last decade, improvements in the investigators' understanding of the molecular basis of cancer have led to the clinical development of protein kinase inhibitors, which target pivotal molecules involved in intracellular signaling pathways implicated in tumorigenesis and tumor progression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Lapatinib and Sorafenib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2009to Aug 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
- Patients with locally advanced, recurrent or metastatic histologically confirmed malignancy refractory to available standard treatment
Who cannot join
- Prior treatment with Lapatinib, Sorafenib or any agents targeting EGFR (other than trastuzumab), Raf, VEGF, or VEGFR
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I and Pharmacokinetics Study of Lapatinib in Combination With Sorafenib in Patients With Advanced Refractory Solid Tumors
Over the last decade, improvements in the investigators' understanding of the molecular basis of cancer have led to the clinical development of protein kinase inhibitors, which target pivotal molecules involved in intracellular signaling pathways implicated in tumorigenesis and tumor progression. Lapatinib is an oral selective and reversible inhibitor of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER-2), which are both frequently altered in human malignant tumors. Sorafenib is an oral multi-kinase inhibitor with a dual-action that prevents tumor cell proliferation and angiogenesis. The investigators suggest that through a complete blockade of ErbB signaling network it may be possible to ''sensitize'' tumor cells to antiangiogenic therapy, by lowering the tumor cell survival threshold, while through inhibition of vascular endothelial growth factor (VEGF) pathway to circumvent the problem of acquired resistance to EGFR inhibitors. Based on this theoretical rationale we decide to test the combination of Lapatinib and Sorafenib. This phase I trial will be undertaken to assess the maximum dose tolerated (MTD), safety/tolerability, pharmacokinetics and antitumor efficacy of this combination in patients with advanced, recurrent or metastatic solid cancers refractory to available standard treatment.
Read the detailed description
This is a dual-agent, prospective, open-label, multi-centric, phase I trial of combination of Lapatinib and Sorafenib in patients with locally advanced, recurrent or metastatic solid tumors. This trial will be conducted to determine the maximum tolerated dose (MTD), safety/tolerability, pharmacokinetics, and antitumor activity of these two agents given together on a continuous schedule, in patients with advanced solid tumors.
Our ambition is to recommend a safe dose regimen of the combination for subsequent larger phase II studies, coinciding with the maximum tolerated dose (MTD).
The maximum tolerated dose (MTD), will be defined as the highest dosage cohort at which no more than one of six patients will be experienced a DLT in the first treatment cycle.
Eligible patients will be enrolled and treated according to the schema, using a 3+3 design (Fibonacci method modified);
- Conditions
- Solid Tumors
- Being tested
- Lapatinib and Sorafenib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapatinib and SorafenibDrug
Also called Tykerb and Nexavar
Comparison of different dosages of two drug
| Study group | Role | What they receive |
|---|---|---|
| Lapatinib and Sorafenib 1° level of dose | Experimental | Lapatinib 750 mg/die + Sorafenib 200 mg bid Receives: Drug: Lapatinib and Sorafenib |
| Lapatinib and Sorafenib 2° level of dose | Experimental | 2° level (II cohort): Lapatinib 1000 mg/die + Sorafenib 200 mg bid Receives: Drug: Lapatinib and Sorafenib |
| Lapatinib and Sorafenib 3° level of dose | Experimental | 3° level (III cohort): Lapatinib 1000 mg/die + Sorafenib 400 mg bid Receives: Drug: Lapatinib and Sorafenib |
| Lapatinib and Sorafenib 4° level of dose | Experimental | 4° level (IV cohort): Lapatinib 1250 mg/die + Sorafenib 400 mg bid Receives: Drug: Lapatinib and Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the dose limiting toxicities (DLTs)and the maximum tolerated dose (MTD) of the combination of Lapatinib and Sorafenib.
Measured: 0ne year
Secondary outcomes (1)
To determine the safety profile of escalating doses of Lapatinib in combination with escalating doses of Sorafenib and and to compare the pharmacokinetics of Lapatinib alone and in combination with Sorafenib
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionJul 2012
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Armando Santoro, MD, Principal investigator, Istituto Clinico Humanitas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00984425
- Sponsor's protocol ID
- ONC-2008-005
- Status last verified
- Nov 2014
- First submitted
- 24 Sep 2009
- Last updated
- 2 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Simonelli M, Zucali PA, Lorenzi E, Rubino L, De Vincenzo F, De Sanctis R, Perrino M, Mancini L, Di Tommaso L, Rimassa L, Masci G, Zuradelli M, Suter MB, Bertossi M, Fattuzzo G, Giordano L, Roncalli MG, Santoro A. Phase I pharmacokinetic and pharmacodynamic study of lapatinib in combination with sorafenib in patients with advanced refractory solid tumors. Eur J Cancer. 2013 Mar;49(5):989-98. doi: 10.1016/j.ejca.2012.10.016. Epub 2012 Nov 9.
PubMed 23146956
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I and Pharmacokinetics Study of Lapatinib in Combination With Sorafenib in Patients With Advanced Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT00984425
- Acronym / sponsor ID
- ONC-2008-005
- Conditions
- Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 25 Sep 2009 (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.
Over the last decade, improvements in the investigators' understanding of the molecular basis of cancer have led to the clinical development of protein kinase inhibitors, which target pivotal molecules involved in intracellular signaling pathways implicated in tumorigenesis and tumor progression. Lapatinib is an oral selective and reversible inhibitor of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER-2), which are both frequently altered in human malignant tumors. Sorafenib is an oral multi-kinase inhibitor with a dual-action that prevents tumor cell proliferation and angiogenesis. The investigators suggest that through a complete blockade of ErbB signaling network it may be possible to ''sensitize'' tumor cells to antiangiogenic therapy, by lowering the tumor cell survival threshold, while through inhibition of vascular endothelial growth factor (VEGF) pathway to circumvent the problem of acquired resistance to EGFR inhibitors. Based on this theoretical rationale we decide to test the combination of Lapatinib and Sorafenib. This phase I trial will be undertaken to assess the maximum dose tolerated (MTD), safety/tolerability, pharmacokinetics and antitumor efficacy of this combination in patients with advanced, recurrent or metastatic solid cancers refractory to available standard treatment.
Detailed description
This is a dual-agent, prospective, open-label, multi-centric, phase I trial of combination of Lapatinib and Sorafenib in patients with locally advanced, recurrent or metastatic solid tumors. This trial will be conducted to determine the maximum tolerated dose (MTD), safety/tolerability, pharmacokinetics, and antitumor activity of these two agents given together on a continuous schedule, in patients with advanced solid tumors.
Our ambition is to recommend a safe dose regimen of the combination for subsequent larger phase II studies, coinciding with the maximum tolerated dose (MTD).
The maximum tolerated dose (MTD), will be defined as the highest dosage cohort at which no more than one of six patients will be experienced a DLT in the first treatment cycle.
Eligible patients will be enrolled and treated according to the schema, using a 3+3 design (Fibonacci method modified);
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Lapatinib and Sorafenib 1° level of dose | Experimental | Drug: Lapatinib and SorafenibLapatinib 750 mg/die + Sorafenib 200 mg bid |
| Lapatinib and Sorafenib 2° level of dose | Experimental | Drug: Lapatinib and Sorafenib2° level (II cohort): Lapatinib 1000 mg/die + Sorafenib 200 mg bid |
| Lapatinib and Sorafenib 3° level of dose | Experimental | Drug: Lapatinib and Sorafenib3° level (III cohort): Lapatinib 1000 mg/die + Sorafenib 400 mg bid |
| Lapatinib and Sorafenib 4° level of dose | Experimental | Drug: Lapatinib and Sorafenib4° level (IV cohort): Lapatinib 1250 mg/die + Sorafenib 400 mg bid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with locally advanced, recurrent or metastatic histologically confirmed malignancy refractory to available standard treatment
Key exclusion criteria (1 listed)
- Prior treatment with Lapatinib, Sorafenib or any agents targeting EGFR (other than trastuzumab), Raf, VEGF, or VEGFR
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 |
|---|---|---|
| Lapatinib and SorafenibAlso: Tykerb and NexavarComparison of different dosages of two drug | Drug | Lapatinib and Sorafenib 1° level of dose, Lapatinib and Sorafenib 2° level of dose, Lapatinib and Sorafenib 3° level of dose, Lapatinib and Sorafenib 4° level of dose |
Primary outcome
To determine the dose limiting toxicities (DLTs)and the maximum tolerated dose (MTD) of the combination of Lapatinib and Sorafenib.
Time frame: 0ne year
1 secondary outcome
To determine the safety profile of escalating doses of Lapatinib in combination with escalating doses of Sorafenib and and to compare the pharmacokinetics of Lapatinib alone and in combination with Sorafenib
Time frame: one year
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 2 Dec 2014.
- Results publication: PubMed 23146956Simonelli M, Zucali PA, Lorenzi E, Rubino L, De Vincenzo F, De Sanctis R, Perrino M, Mancini L, Di Tommaso L, Rimassa L, Masci G, Zuradelli M, Suter MB, Bertossi M, Fattuzzo G, Giordano L, Roncalli MG, Santoro A. Phase I pharmacokinetic and pharmacodynamic study of lapatinib in combination with sorafenib in patients with advanced refractory solid tumors. Eur J Cancer. 2013 Mar;49(5):989-98. doi: 10.1016/j.ejca.2012.10.016. Epub 2012 Nov 9.
Related trials for Solid Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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.
Armando Santoro, MD principal investigator
Istituto Clinico Humanitas
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 Lapatinib and Sorafenib in people with Solid Tumors, run by Istituto Clinico Humanitas at 1 site in Italy.
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 1 inclusion and 1 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 2 Dec 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 Italy. 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?
To determine the dose limiting toxicities (DLTs)and the maximum tolerated dose (MTD) of the combination of Lapatinib and Sorafenib. (time frame: 0ne year). 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 NCT00984425, which also lists 1 linked publication.
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 2 Dec 2014.