Relapsed Malignant MesotheliomaPhase 1NCT02372227
A Phase 1 Dose Escalation Study of VS-5584 Administered in Combination With VS-6063, in Subjects With Relapsed Malignant Mesothelioma
A Phase 1 study testing VS-5584 and VS-6063 in people with Relapsed Malignant Mesothelioma, run by Verastem, Inc. at 4 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate rising dose levels of VS-5584 administered in combination with a fixed dose of VS-6063 in subjects with relapsed malignant mesothelioma to determine a recommended Phase 2 dose (RP2D) for further development of this combination in this indication. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Malignant Mesothelioma
- What is being tested?
- VS-5584 and VS-6063
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Jan 2015to Oct 2015
- 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
- Histopathologically-confirmed diagnosis of malignant mesothelioma (pleural or peritoneal). Must have disease that has relapsed following at least one prior line of chemotherapy.
- Must have received at least 3 cycles of first-line chemotherapy.
- Evaluable or measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST).
- Must have archival tumor tissue available for biomarker analysis. A study-specific tumor core biopsy, pleural effusion or ascites sample must be obtained prior to treatment if archival tissue is not available.
- Performance status according to the Karnofsky Performance Scale ≥70%.
- Fasting blood glucose of ≤ 140 mg/dL (7.8 mmol/L).
Show all 9Show fewer
- Adequate renal function (creatinine ≤ 1.5x upper limit of normal [ULN]) and/or glomerular filtration rate (GFR) of ≥50 mL/min.
- Adequate hepatic function (total bilirubin ≤ 1.5x ULN; AST and ALT ≤ 3x ULN).
- Adequate bone marrow function (hemoglobin ≥9.0 g/dL; platelets ≥100 x10^9 cells/L; absolute neutrophil count ≥1.5x10^9 cells/L) without the use of hematopoietic growth factors.
Who cannot join
- Have had a previous extra pleural pneumonectomy (EPP).
- Gastrointestinal condition which could interfere with the swallowing or absorption of study drug.
- Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases).
- Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug.
- Any evidence of serious active infection.
- Undergoing active treatment for a secondary malignancy.
Show all 12Show fewer
- Cancer-directed therapy (chemotherapy, radiotherapy) within 21 days of the first dose of study drug or 5 half-lives, whichever is shorter.
- Major surgery within 28 days prior to the first dose of study drug.
- Acute or chronic pancreatitis.
- Diabetes mellitus requiring insulin treatment or subjects with a hemoglobin A1C (HbA1C) >7%.
- History or evidence of cardiac risk.
- Known history of malignant hypertension.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States2 sites
The University of Chicago Medical Center
Chicago, Illinois, 60637
Memorial Sloane Kettering Cancer Center
New York, New York, 10065
United Kingdom2 sites
University of Leicester
Leicester
The Institute of Cancer Research
Sutton Surrey
About this study
Official title: A Phase 1 Dose Escalation Study of VS-5584, a Dual PI3K/mTOR Inhibitor, Administered With a Fixed Dose of VS-6063, a Focal Adhesion Kinase Inhibitor, in Subjects With Relapsed Malignant Mesothelioma
The purpose of this study is to evaluate rising dose levels of VS-5584 administered in combination with a fixed dose of VS-6063 in subjects with relapsed malignant mesothelioma to determine a recommended Phase 2 dose (RP2D) for further development of this combination in this indication.
Read the detailed description
This study is comprised of 2 sequential parts: Part 1 (Dose Escalation of VS-5584) and Part 2 (Expansion). Up to 56 evaluable subjects (i.e., subjects who complete at least 1 cycle [21 days] of therapy) will be enrolled, assuming that:
- Up to 6 dose levels of VS-5584 are studied in Part 1 (Dose Escalation of VS-5584) in combination with a fixed dose of VS-6063 at 400 mg twice daily (BID) with a maximum of 6 subjects enrolled per VS-5584 dose level, for a total of up to 36 subjects (exclusive of replacement subjects).
- Up to an additional 20 evaluable subjects may be enrolled in Part 2, the expansion portion of the study. Subjects will be treated with VS-5584 at the RP2D and schedule determined in the dose escalation portion of the study in combination with a fixed dose of VS-6063.
- Conditions
- Relapsed Malignant Mesothelioma
- Being tested
- VS-5584 and VS-6063
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VS-5584 and VS-6063Drug
Starting dose of VS-5584 will be 20mg taken once daily, 3x/week of each 21 day cycle. All subjects will also receive 2x/day treatment with 400mg VS-6063 in 21 day cycles. Number of Cycles: until progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| VS-5584 and VS-6063 | Experimental | Not described Receives: Drug: VS-5584 and VS-6063 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of VS-5584 and VS-6063 in a 21 day cycle
Measured: 6 months
Safety and tolerability of the combination of VS-5584 and VS-6063
Dose Escalation Phase and Expansion Phase: A composite by dose level to include incidence of AEs, SAEs (overall and severity), laboratory abnormalities, ECGs, vital signs, Karnofsky Performance Status, dose interruptions and dose reductions as a measure of safety and tolerability
Measured: 16 months
Secondary outcomes (7)
Pharmacokinetics of VS-5584 & VS-6063 maximum observed plasma concentration (Cmax)
Measured: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 plasma area under the curve from time zero to last quantifiable concentration (AUClast)
Measured: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 time to reach maximum observed concentration (Tmax)
Measured: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 area under the curve from time zero to extrapolated infinite time (AUCO-inf)
Measured: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 apparent oral clearance (CL/F)
Measured: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 apparent volume of distribution (Vz/F)
Measured: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 trough plasma concentration
Measured: 0-48 hours per patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2015 (estimated)
- Study startJan 2015
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Malignant MesotheliomaStudies of the same condition, open and under way.
- More trials run by Verastem, Inc.The 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
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Verastem, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hagop Youssoufian, Study chair, Verastem, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02372227
- Sponsor's protocol ID
- VS-6063-104
- Status last verified
- Jan 2017
- First submitted
- 30 Jan 2015
- Last updated
- 30 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation Study of VS-5584, a Dual PI3K/mTOR Inhibitor, Administered With a Fixed Dose of VS-6063, a Focal Adhesion Kinase Inhibitor, in Subjects With Relapsed Malignant Mesothelioma
- ClinicalTrials.gov ID
- NCT02372227
- Acronym / sponsor ID
- VS-6063-104
- Conditions
- Relapsed Malignant Mesothelioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Verastem, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2015
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 26 Feb 2015 (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 evaluate rising dose levels of VS-5584 administered in combination with a fixed dose of VS-6063 in subjects with relapsed malignant mesothelioma to determine a recommended Phase 2 dose (RP2D) for further development of this combination in this indication.
Detailed description
This study is comprised of 2 sequential parts: Part 1 (Dose Escalation of VS-5584) and Part 2 (Expansion). Up to 56 evaluable subjects (i.e., subjects who complete at least 1 cycle [21 days] of therapy) will be enrolled, assuming that:
- Up to 6 dose levels of VS-5584 are studied in Part 1 (Dose Escalation of VS-5584) in combination with a fixed dose of VS-6063 at 400 mg twice daily (BID) with a maximum of 6 subjects enrolled per VS-5584 dose level, for a total of up to 36 subjects (exclusive of replacement subjects).
- Up to an additional 20 evaluable subjects may be enrolled in Part 2, the expansion portion of the study. Subjects will be treated with VS-5584 at the RP2D and schedule determined in the dose escalation portion of the study in combination with a fixed dose of VS-6063.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VS-5584 and VS-6063 | Experimental | Drug: VS-5584 and VS-6063 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histopathologically-confirmed diagnosis of malignant mesothelioma (pleural or peritoneal). Must have disease that has relapsed following at least one prior line of chemotherapy.
- Must have received at least 3 cycles of first-line chemotherapy.
- Evaluable or measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST).
- Must have archival tumor tissue available for biomarker analysis. A study-specific tumor core biopsy, pleural effusion or ascites sample must be obtained prior to treatment if archival tissue is not available.
- Performance status according to the Karnofsky Performance Scale ≥70%.
Key exclusion criteria (12 listed)
- Have had a previous extra pleural pneumonectomy (EPP).
- Gastrointestinal condition which could interfere with the swallowing or absorption of study drug.
- Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases).
- Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug.
- Any evidence of serious active infection.
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 |
|---|---|---|
| VS-5584 and VS-6063Starting dose of VS-5584 will be 20mg taken once daily, 3x/week of each 21 day cycle. All subjects will also receive 2x/day treatment with 400mg VS-6063 in 21 day cycles. Number of Cycles: until progression or unacceptable toxicity develops. | Drug | VS-5584 and VS-6063 |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 6 months
Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of VS-5584 and VS-6063 in a 21 day cycle
Safety and tolerability of the combination of VS-5584 and VS-6063
Time frame: 16 months
Dose Escalation Phase and Expansion Phase: A composite by dose level to include incidence of AEs, SAEs (overall and severity), laboratory abnormalities, ECGs, vital signs, Karnofsky Performance Status, dose interruptions and dose reductions as a measure of safety and tolerability
7 secondary outcomes
Pharmacokinetics of VS-5584 & VS-6063 maximum observed plasma concentration (Cmax)
Time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 plasma area under the curve from time zero to last quantifiable concentration (AUClast)
Time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 time to reach maximum observed concentration (Tmax)
Time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 area under the curve from time zero to extrapolated infinite time (AUCO-inf)
Time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 apparent oral clearance (CL/F)
Time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 apparent volume of distribution (Vz/F)
Time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 trough plasma concentration
Time frame: 0-48 hours per patient
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2017.
Related trials for Relapsed Malignant Mesothelioma
Active, not recruitingPhase 1/2
Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma
Epithelioid Mesothelioma, Pleural Malignant Mesothelioma
RecruitingPhase 1
TLN-499 in Combination With Venetoclax in Patients With Relapsed/Refractory Solid Tumors
Small Cell Lung Cancer ( SCLC ), Neuroendocrine Cancer
RecruitingPhase 2
Evaluating Ivonescimab as a Potential Treatment for Pleural Mesothelioma Patients Whose Cancer Has Returned After Previous Immunotherapy and Chemotherapy
Pleural Mesotheliomas
Not yet recruitingPhase 2
SELECTmeso A Trial for Patients With Relapsed Malignant Mesothelioma SELECTmeso1 A Trial of BMS-986504 in Patients With MTAP-deficient Relapsed Mesothelioma
Mesothelioma
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.
Hagop Youssoufian study chair
Verastem, Inc.
4 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 VS-5584 and VS-6063 in people with Relapsed Malignant Mesothelioma, run by Verastem, Inc. at 4 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?
The sponsor lists 9 inclusion and 12 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: stopped early, as of the sponsor's last update on 30 Jan 2017. 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, United Kingdom. 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 was stopped early. Results are not available in the source record.
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?
Incidence of dose-limiting toxicities (DLTs) (time frame: 6 months). 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?
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 30 Jan 2017.