NeoplasmsPhase 1NCT01973868
Safety and Pharmacokinetics of Regorafenib and Cetuximab in Combination
A Phase 1 study testing Regorafenib (Stivarga, BAY73-4506) and Cetuximab (ERBITUX) in people with Neoplasms, run by Bayer at 4 sites in United States.
Trial summary
To establish safety, tolerability and pharmacokinetics of regorafenib and cetuximab in combination, and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Regorafenib (Stivarga, BAY73-4506) and Cetuximab (ERBITUX)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 4 sitesUnited States
- Study dates
- 21 Nov 2013to 3 Apr 2018
- 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 histologically or cytologically confirmed, locally advanced or metastatic solid tumors who are not candidates for standard therapy or in whom regorafenib or cetuximab is considered a standard treatment. Patients with metastatic colorectal cancer (mCRC) must have a record of K-ras gene mutational analysis available and no K-ras mutation is present.
- Male or female patients ≥ 18 years of age
- Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment
- Life expectancy of at least 3 months
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment:
- Platelet count ≥ 100,000/cubic millimeters (mm3), hemoglobin (Hb) ≥ 8.5 g/dl, leukocyte count > 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,000/mm3
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- Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Mildly elevated total bilirubin (< 6 mg/dL) is allowed if Gilbert's syndrome is documented.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
- Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects whose cancer involves their liver).
- Amylase and lipase ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 times ULN and creatinine clearance (CLcr) ≥ 30 mL/min according to the Cockroft-Gault formula
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Who cannot join
- Prior treatment with Regorafenib
- Prior discontinuation of cetuximab treatment due to toxicity or intolerance of cetuximab
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
- Non-healing wound, ulcer, or bone fracture
- Systemic anticancer therapy within 28 days
- Patients unable to swallow and retain oral medications
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Colorado Hospital
Aurora, Colorado, 80045
University of Southern California
Los Angeles, California, 90033
University of Pittsburgh Medical Center Health System
Pittsburgh, Pennsylvania, 15232
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase 1b, Multi-center, Non-randomized, Open Label, Dose Escalation Design Study of Regorafenib (BAY73-4506) in Combination With Cetuximab in Subjects With Locally Advanced or Metastatic Solid Tumors Who Are Not Candidates for Standard Therapy or in Whom Regorafenib or Cetuximab is Considered as a Standard Treatment
To establish safety, tolerability and pharmacokinetics of regorafenib and cetuximab in combination, and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
- Conditions
- Neoplasms
- Being tested
- Regorafenib (Stivarga, BAY73-4506), Cetuximab (ERBITUX)
- Keywords
- Regorafenib, Cetuximab, Solid tumors, Cancer, Safety, Tolerability, Pharmacokinetics
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib (Stivarga, BAY73-4506)Drug
Cetuximab (ERBITUX)Drug
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Experimental | Regorafenib will be administered once daily on Days 1-21 of each 28-day Cycle (3 weeks on / 1 week off). The starting dose of regorafenib is 120 mg q.d., if this is tolerable in combination with cetuximab the dose will be escalated to 160 mg q.d.; if it is not tolerated the dose will be de-escalated to 80 mg q.d.
Subjects will receive an initial i.v. infusion of cetuximab (loading dose of 400 mg/ m2 BSA) on Pre-cycle Day -7.
The treatment of regorafenib in combination with cetuximab maintenance dose (250 mg/m2 BSA) starts on Cycle 1 Day 1.
Cetuximab infusions will be given in a once-weekly dosing-regimen as approved. Receives: Drug: Regorafenib (Stivarga, BAY73-4506); Drug: Cetuximab (ERBITUX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of regorafenib in combination with cetuximab
MTD is defined as the maximum dose at which the incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 20 %, or as the maximum dose administered, whichever is achieved first during dose escalation
Measured: 1 month
Number of participants with Adverse Events as a measure of safety and tolerability
Measured: Up to 2 years or longer
Cmax,md (Cmax after multiple dose) for regorafenib and cetuximab
Measured: Multiple time points on Day 15
AUC(0-24)md (AUC from time zero to 24 hours after multiple-dose administration) for regorafenib
Measured: Multiple time points on Day 15
AUC(0-26)md (AUC from time zero to 26 hours after multiple-dose administration) for cetuximab
Measured: Multiple time points on Day 15
Secondary outcomes (4)
Tumor response according to RECIST 1.1
Measured: Up to 2 years or longer
tmax,md (tmax after multiple-dose administration) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab
Measured: Multiple time points on Day 15
tlast,md (tlast after multiple dosing) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab
Measured: Multiple time points on Day 15
Cmax,md for metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752)
Measured: Multiple time points on Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2013 (estimated)
- Study start21 Nov 2013
- Primary completion31 Jan 2017
- Study completion3 Apr 2018
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 NeoplasmsStudies of the same condition, open and under way.
- More trials run by BayerThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01973868
- Sponsor's protocol ID
- 16547
- Status last verified
- Apr 2019
- First submitted
- 28 Oct 2013
- Last updated
- 9 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Weekes C, Lockhart AC, Lee JJ, Sturm I, Cleton A, Huang F, Lenz HJ. A phase 1b study evaluating the safety and pharmacokinetics of regorafenib in combination with cetuximab in patients with advanced solid tumors. Int J Cancer. 2019 Nov 1;145(9):2450-2458. doi: 10.1002/ijc.32317. Epub 2019 Jun 14.
PubMed 30958892
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Multi-center, Non-randomized, Open Label, Dose Escalation Design Study of Regorafenib (BAY73-4506) in Combination With Cetuximab in Subjects With Locally Advanced or Metastatic Solid Tumors Who Are Not Candidates for Standard Therapy or in Whom Regorafenib or Cetuximab is Considered as a Standard Treatment
- ClinicalTrials.gov ID
- NCT01973868
- Acronym / sponsor ID
- 16547
- Conditions
- Neoplasms
- Keywords
- Regorafenib, Cetuximab, Solid tumors, Cancer, Safety, Tolerability, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 21 Nov 2013 (actual)
- Primary completion
- 31 Jan 2017 (actual)
- Study completion
- 3 Apr 2018 (actual)
- First posted
- 1 Nov 2013 (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.
To establish safety, tolerability and pharmacokinetics of regorafenib and cetuximab in combination, and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib | Experimental | Drug: Regorafenib (Stivarga, BAY73-4506), Drug: Cetuximab (ERBITUX)Regorafenib will be administered once daily on Days 1-21 of each 28-day Cycle (3 weeks on / 1 week off). The starting dose of regorafenib is 120 mg q.d., if this is tolerable in combination with cetuximab the dose will be escalated to 160 mg q.d.; if it is not tolerated the dose will be de-escalated to 80 mg q.d. Subjects will receive an initial i.v. infusion of cetuximab (loading dose of 400 mg/ m2 BSA) on Pre-cycle Day -7. The treatment of regorafenib in combination with cetuximab maintenance dose (250 mg/m2 BSA) starts on Cycle 1 Day 1. Cetuximab infusions will be given in a once-weekly dosing-regimen as approved. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors who are not candidates for standard therapy or in whom regorafenib or cetuximab is considered a standard treatment. Patients with metastatic colorectal cancer (mCRC) must have a record of K-ras gene mutational analysis available and no K-ras mutation is present.
- Male or female patients ≥ 18 years of age
- Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment
- Life expectancy of at least 3 months
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment:
Key exclusion criteria (6 listed)
- Prior treatment with Regorafenib
- Prior discontinuation of cetuximab treatment due to toxicity or intolerance of cetuximab
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
- Non-healing wound, ulcer, or bone fracture
- Systemic anticancer therapy within 28 days
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 |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Drug | Regorafenib |
| Cetuximab (ERBITUX) | Drug | Regorafenib |
Primary outcome
Maximum tolerated dose (MTD) of regorafenib in combination with cetuximab
Time frame: 1 month
MTD is defined as the maximum dose at which the incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 20 %, or as the maximum dose administered, whichever is achieved first during dose escalation
Number of participants with Adverse Events as a measure of safety and tolerability
Time frame: Up to 2 years or longer
Cmax,md (Cmax after multiple dose) for regorafenib and cetuximab
Time frame: Multiple time points on Day 15
AUC(0-24)md (AUC from time zero to 24 hours after multiple-dose administration) for regorafenib
Time frame: Multiple time points on Day 15
AUC(0-26)md (AUC from time zero to 26 hours after multiple-dose administration) for cetuximab
Time frame: Multiple time points on Day 15
4 secondary outcomes
Tumor response according to RECIST 1.1
Time frame: Up to 2 years or longer
tmax,md (tmax after multiple-dose administration) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab
Time frame: Multiple time points on Day 15
tlast,md (tlast after multiple dosing) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab
Time frame: Multiple time points on Day 15
Cmax,md for metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752)
Time frame: Multiple time points on Day 15
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 9 Apr 2019.
- Derived from this study: PubMed 30958892Weekes C, Lockhart AC, Lee JJ, Sturm I, Cleton A, Huang F, Lenz HJ. A phase 1b study evaluating the safety and pharmacokinetics of regorafenib in combination with cetuximab in patients with advanced solid tumors. Int J Cancer. 2019 Nov 1;145(9):2450-2458. doi: 10.1002/ijc.32317. Epub 2019 Jun 14.
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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.
Bayer Study Director study director
Bayer
4 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 Regorafenib (Stivarga, BAY73-4506) and Cetuximab (ERBITUX) in people with Neoplasms, run by Bayer at 4 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 12 inclusion and 6 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 9 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
Maximum tolerated dose (MTD) of regorafenib in combination with cetuximab (time frame: 1 month). The study lists 5 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 NCT01973868, 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 9 Apr 2019.