Advanced MalignancyPhase 1NCT02110355
A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma
A Phase 1 study testing AMG 232, Trametinib and Dabrafenib in people with Advanced Malignancy and Advanced Solid Tumors, run by Kartos Therapeutics, Inc. at 7 sites in 2 countries.
Trial summary
Phase 1b/2a, open-label, sequential dose escalation and expansion study of AMG 232 in combination with trametinib and dabrafenib in subjects with metastatic melanoma followed by a direct comparison of AMG 232 combined with trametinib and dabrafenib versus trametinib combined with dabrafenib alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignancy, Advanced Solid Tumors, Cancer
- What is being tested?
- AMG 232, Trametinib and Dabrafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 19 Dec 2014to 27 Dec 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
Inclusion Criteria: Subjects must have histologically or cytologically confirmed metastatic cutaneous or mucosal melanoma, Able to swallow and retain orally administered medication, Adequate hematological, renal, hepatic, and coagulation laboratory assessments Exclusion Criteria: Clinically significant bleeding within 4 weeks of screening, Current use of warfarin, factor Xa inhibitors, and direct thrombin inhibitors, Infection requiring anti-infective treatments within 1 week of study enrollment, Anti-tumor therapy, Major surgery within 28 days
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States5 sites
Research Site
Aurora, Colorado, 80045
Research Site
Boston, Massachusetts, 02114
Research Site
Chapel Hill, North Carolina, 27599
Research Site
Los Angeles, California, 90095
Research Site
Nashville, Tennessee, 37232
Australia2 sites
Research Site
Melbourne, Victoria, 3000
Research Site
North Sydney, New South Wales, 2060
About this study
Official title: A Phase 1b/2a Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 232 Combined With Trametinib and Dabrafenib or Trametinib in Adult Subjects With Metastatic Cutaneous Melanoma
Phase 1b/2a, open-label, sequential dose escalation and expansion study of AMG 232 in combination with trametinib and dabrafenib in subjects with metastatic melanoma followed by a direct comparison of AMG 232 combined with trametinib and dabrafenib versus trametinib combined with dabrafenib alone.
Read the detailed description
The study will be conducted in 3 parts: Part 1 - Dose Escalation, Part 2 - Dose Expansion and Part 3, a randomized Phase 2a.
In both part 1 and 2, subjects will be enrolled open-label into 1 of 2 arms. For both Arm 1 and Arm 2, the part 1 dose escalation is aimed at determining an AMG 232 maximum tolerated dose (MTD) with a fixed dose of the combination drug(s) and evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of each combination. Part 2 dose expansion will enroll subjects to receive therapy with a dose and schedule of AMG 232 selected from the corresponding part 1 dose escalation. In part 2 subjects will be enrolled to confirm safety and tolerability and to assess clinical activity prior to proceeding to Part 3, Phase 2a. In Phase 2a, Subjects will be randomized open-label in a 1:1 ratio to receive AMG 232 in combination with trametinib plus dabrafenib versus trametinib plus dabrafenib alone.
Only Part 1 of the study was enrolled and the study did not proceed into Phase 2.
- Conditions
- Advanced Malignancy, Advanced Solid Tumors, Cancer, Oncology, Oncology Patients, Tumors
- Being tested
- AMG 232, Trametinib, Dabrafenib
- Keywords
- Metastatic melanoma
- Medical subject headings
- Neoplasms, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 232Drug
Given as an oral tablet in escalating doses
TrametinibDrug
Trametinib is an anti-cancer agent
DabrafenibDrug
Dabrafenib is an anti-cancer agent
| Study group | Role | What they receive |
|---|---|---|
| AMG 232 with Trametinib and Dabrabenib | Experimental | Arm 1 of Part 1 and 2 and Part 3 Receives: Drug: AMG 232; Drug: Trametinib; Drug: Dabrafenib |
| AMG 232 with Trametinib | Experimental | Arm 2 of Part 1 and 2 Receives: Drug: AMG 232; Drug: Trametinib |
| Trametinib and Dabrafenib | Active comparator | Part 3 Receives: Drug: Trametinib; Drug: Dabrafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subject incidence of treatment-emergent adverse events, Results of safety laboratory tests, vital sign measurements, ECG measurements, PK parameters; Progression-free Survival Rate
Incidence and grade of treatment-emergent adverse events, including dose-limiting toxicities; AMG 232, trametinib, dabrafenib, and metabolite PK parameters; progression-free Survival
Measured: 36 months
Secondary outcomes (1)
Time to and duration of overall response and duration of stable disease measured by CT or MRI and assessed per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, Progression-free and Overall Survival
Objective Tumor Response
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2014 (estimated)
- Study start19 Dec 2014
- Primary completion27 Dec 2018
- Study completion27 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kartos Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- John Mei, Study director, Kartos Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02110355
- Sponsor's protocol ID
- 20120238
- Status last verified
- Mar 2021
- First submitted
- 8 Apr 2014
- Last updated
- 26 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2a Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 232 Combined With Trametinib and Dabrafenib or Trametinib in Adult Subjects With Metastatic Cutaneous Melanoma
- ClinicalTrials.gov ID
- NCT02110355
- Acronym / sponsor ID
- 20120238
- Conditions
- Advanced Malignancy, Advanced Solid Tumors, Cancer, Oncology, Oncology Patients, Tumors
- Keywords
- Metastatic melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Kartos Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 19 Dec 2014 (actual)
- Primary completion
- 27 Dec 2018 (actual)
- Study completion
- 27 Dec 2018 (actual)
- First posted
- 10 Apr 2014 (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.
Phase 1b/2a, open-label, sequential dose escalation and expansion study of AMG 232 in combination with trametinib and dabrafenib in subjects with metastatic melanoma followed by a direct comparison of AMG 232 combined with trametinib and dabrafenib versus trametinib combined with dabrafenib alone.
Detailed description
The study will be conducted in 3 parts: Part 1 - Dose Escalation, Part 2 - Dose Expansion and Part 3, a randomized Phase 2a.
In both part 1 and 2, subjects will be enrolled open-label into 1 of 2 arms. For both Arm 1 and Arm 2, the part 1 dose escalation is aimed at determining an AMG 232 maximum tolerated dose (MTD) with a fixed dose of the combination drug(s) and evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of each combination. Part 2 dose expansion will enroll subjects to receive therapy with a dose and schedule of AMG 232 selected from the corresponding part 1 dose escalation. In part 2 subjects will be enrolled to confirm safety and tolerability and to assess clinical activity prior to proceeding to Part 3, Phase 2a. In Phase 2a, Subjects will be randomized open-label in a 1:1 ratio to receive AMG 232 in combination with trametinib plus dabrafenib versus trametinib plus dabrafenib alone.
Only Part 1 of the study was enrolled and the study did not proceed into Phase 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AMG 232 with Trametinib and Dabrabenib | Experimental | Drug: AMG 232, Drug: Trametinib, Drug: DabrafenibArm 1 of Part 1 and 2 and Part 3 |
| AMG 232 with Trametinib | Experimental | Drug: AMG 232, Drug: TrametinibArm 2 of Part 1 and 2 |
| Trametinib and Dabrafenib | Active comparator | Drug: Trametinib, Drug: DabrafenibPart 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| AMG 232Given as an oral tablet in escalating doses | Drug | AMG 232 with Trametinib, AMG 232 with Trametinib and Dabrabenib |
| TrametinibTrametinib is an anti-cancer agent | Drug | AMG 232 with Trametinib, AMG 232 with Trametinib and Dabrabenib, Trametinib and Dabrafenib |
| DabrafenibDabrafenib is an anti-cancer agent | Drug | AMG 232 with Trametinib and Dabrabenib, Trametinib and Dabrafenib |
Primary outcome
Subject incidence of treatment-emergent adverse events, Results of safety laboratory tests, vital sign measurements, ECG measurements, PK parameters; Progression-free Survival Rate
Time frame: 36 months
Incidence and grade of treatment-emergent adverse events, including dose-limiting toxicities; AMG 232, trametinib, dabrafenib, and metabolite PK parameters; progression-free Survival
1 secondary outcome
Time to and duration of overall response and duration of stable disease measured by CT or MRI and assessed per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, Progression-free and Overall Survival
Time frame: 36 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 26 Mar 2021.
- Individual participant dataSharing planned: No
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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.
John Mei study director
Kartos Therapeutics
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 232, Trametinib and Dabrafenib in people with Advanced Malignancy and Advanced Solid Tumors, run by Kartos Therapeutics, Inc. at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 26 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Australia. 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?
Subject incidence of treatment-emergent adverse events, Results of safety laboratory tests, vital sign measurements, ECG measurements, PK parameters; Progression-free Survival Rate (time frame: 36 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 26 Mar 2021.