Advanced Solid TumorPhase 1NCT02644278
First-in-Human Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-984 in Combination With Chemotherapy
A Phase 1 study testing VX-984 120 mg + PLD 40 mg/m^2, VX-984 240 mg + PLD 40 mg/m^2 and VX-984 480 mg + PLD 40 mg/m^2 in people with Advanced Solid Tumor, run by EMD Serono Research & Development Institute, Inc. at 5 sites in United States.
Trial summary
The purpose of this study was to evaluate the safety and tolerability of VX-984 (M9831) administered alone and in combination with pegylated liposomal doxorubicin (PLD), and to determine the maximum tolerated dose (MTD) and preliminary evidence of efficacy of VX-984 in combination with PLD in participants with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- VX-984 120 mg + PLD 40 mg/m^2, VX-984 240 mg + PLD 40 mg/m^2 and VX-984 480 mg + PLD 40 mg/m^2
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 5 sitesUnited States
- Study dates
- 29 Feb 2016to 19 Oct 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Participants (male and female for Part A and female for Part B) were at least 18 year of age.
- Part A Participants with histologically or cytologically confirmed malignant advanced solid tumors, who had progressed on at least 1 prior chemotherapy, and for whom either
- No standard care available
- PLD at the dose and schedule being used might be considered standard of care
- Part B
- Participants with histologically confirmed advanced primary endometrial cancer (locally advanced and incurable endometrial cancer that had been treated with surgery and/or radiation or is ineligible for such treatment), or recurrent or metastatic endometrial cancer, and
Show all 11Show fewer
- Completed 1 line of chemotherapy treatment with a platinum-containing regimen in the advanced setting
- Measurable disease according to RECIST criteria (Version 1.1)
- Life expectancy of at least 12 weeks
- Hematological and biochemical indices within acceptable ranges shown at screening.
- Normal left ventricular ejection fraction on screening assessed by transthoracic echocardiogram or multiple gated acquisition (MUGA) scan
Who cannot join
- Previous radiotherapy (unless brachytherapy), endocrine therapy, chemotherapy, or exposure to investigational medicinal products during the 4 weeks (6 weeks for nitrosoureas and Mitomycin-C) or 4 drug half-lives before the planned administration of the first dose of study drug, whichever is greater. Previous immunotherapy during the 4 weeks before the planned administration of the first dose of study drug.
- For Part B only:
- Participants with uterine carcinosarcoma
- Prior anthracycline therapy
- More than 1 prior chemotherapy regimen (a participant was received first- line carboplatin and taxane and then received the same taxane second- line were considered to have had 1 prior chemotherapy regimen)
- Unresolved toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater from previous anti-cancer therapy or radiotherapy
Show all 16Show fewer
- History of spinal cord compression or brain metastases, unless asymptomatic, treated, stable, and not requiring treatment with steroids for at least 4 weeks before the planned administration of the first dose of study drug. Any history of leptomeningeal metastases.
- Female participants who was pregnant or lactating at Screening, or planned to become pregnant while on study or within 6 months after the last dose of study drug
- Female participants of childbearing potential were adhere to contraception guidelines as outlined in the protocol. Female participants were considered to be of nonchildbearing potential if they had undergone surgical hysterectomy or bilateral oophorectomy or had been amenorrheic for more than 2 years with a screening serum follicle-stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females
- Male participants with pregnant or lactating partners or partners who planned to become pregnant while on study or within 6 months after the planned administration of the last dose of study drug
- Major surgery ≤4 weeks before first dose of study drug, or incomplete recovery from a prior major surgical procedure
- Cardiac conditions
- Prior bone marrow transplant
- Extensive radiotherapy (to greater than 15% of bone marrow)
- Any other condition that in the investigator's opinion would not make the participant a good candidate for the clinical study,
- Part B: Current active malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Prior cancer in remission for 2 years or more would not be excluded.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Study site
Boston, Massachusetts, 02215
Study site
Dallas, Texas, 75246
Study site
Houston, Texas, 77030
Study site
Nashville, Tennessee, 37203
Study site
Scottsdale, Arizona, 85258
About this study
Official title: An Open-Label, Phase 1, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-984 in Combination With Chemotherapy in Subjects With Advanced Solid Tumors
The purpose of this study was to evaluate the safety and tolerability of VX-984 (M9831) administered alone and in combination with pegylated liposomal doxorubicin (PLD), and to determine the maximum tolerated dose (MTD) and preliminary evidence of efficacy of VX-984 in combination with PLD in participants with advanced solid tumors.
- Conditions
- Advanced Solid Tumor
- Being tested
- VX-984 120 mg + PLD 40 mg/m^2, VX-984 240 mg + PLD 40 mg/m^2, VX-984 480 mg + PLD 40 mg/m^2, VX-984 720 mg + PLD 40 mg/m^2
- Keywords
- VX15-984-001, VX-984, M9831, Advanced Solid Tumor, Pegylated liposomal doxorubicin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VX-984 120 mg + PLD 40 mg/m^2Drug
Also called M9831
Participants received VX-984 orally 120 milligram (mg) orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m^2.
VX-984 240 mg + PLD 40 mg/m^2Drug
Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m^2.
VX-984 480 mg + PLD 40 mg/m^2Drug
Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m^2.
VX-984 720 mg + PLD 40 mg/m^2Drug
Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m^2.
| Study group | Role | What they receive |
|---|---|---|
| VX-984 120 mg + PLD 40 mg/m^2 | Experimental | Not described Receives: Drug: VX-984 120 mg + PLD 40 mg/m^2 |
| VX-984 240 mg + PLD 40 mg/m^2 | Experimental | Not described Receives: Drug: VX-984 240 mg + PLD 40 mg/m^2 |
| VX-984 480 mg + PLD 40 mg/m^2 | Experimental | Not described Receives: Drug: VX-984 480 mg + PLD 40 mg/m^2 |
| VX-984 720 mg + PLD 40 mg/m^2 | Experimental | Not described Receives: Drug: VX-984 720 mg + PLD 40 mg/m^2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-Emergent adverse events (TEAEs) were defined as AEs that were reported or worsened on or after the start of study drug dosing through the 28-day Safety Follow-up visit. TEAEs included both Serious TEAEs and non-serious TEAEs.
Measured: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
Part A: Number of Participants Who Experienced Dose Limiting Toxicity (DLT)
DLT was defined using National cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 as any of the following toxicities: Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (>=) 3 febrile neutropenia; Grade 4 or Grade 3 thrombocytopenia with bleeding. Grade >= 3 uncontrolled nausea/vomiting and/or diarrhea despite adequate and optimal treatment and Grade >= 3 any non- hematological adverse event (AE), except the aforementioned gastrointestinal events and alopecia.
Measured: Cycle 1 (each cycle is 28 days)
Part A: Number of Participants With Toxicity Grade 3 or Higher in Laboratory Abnormalities
The laboratory measurements included hematology and serum chemistry. It had been graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 into Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Life-threatening) and Grade 5 = death. Participants with grade 3 or higher were reported.
Measured: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
Part A: Maximum Tolerated Dose (MTD) of VX-984 in Combination With Pegylated Liposomal Doxorubicin (PLD)
The MTD was defined as the combination dose associated with the highest probability that Dose limiting toxicity (DLT) events will occur in 16.6 percent to less than 33.3 percent participants as the combination dose that not exceeded the overdose criterion (more than 25 percent probability that DLT events occurred less than or equal to (>=) 33 percent of participants. DLT was defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0.
Measured: Up to Cycle 1 Day 28 (each cycle is 28 days)
Part A: Number of Participants With Clinical Significant Abnormalities in Vital Signs
Vital signs assessment included blood pressure, pulse rate and body temperature. Clinical significance was determined by the investigator. Number of participants with clinical significant abnormalities in vital Signs reported here.
Measured: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
Part A: Number of Participants With Clinical Significant Abnormalities Echocardiograms
Echocardiogram is a graphic outline of the heart's movement. Clinical significance was determined by the investigator. Number of participants with clinical significant abnormalities in Echocardiograms reported here.
Measured: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
Part A: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram(ECG) Parameters
ECG parameters included heart rate, pulse rate, QRS,QT, RR, QTcB and QTcF. Clinical significance was determined by the investigator. Number of participants with clinical significant abnormalities in ECG parameters reported here.
Measured: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
Secondary outcomes (8)
Part A: Area Under Plasma Concentration (AUC) During a Dosing Interval of VX-984
AUC is the area under the plasma concentration curve within 1 dosing interval.
Measured: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)
Part A: Maximum Observed Plasma Concentration (Cmax) of VX-984
Pharmacokinetic PK parameter Cmax was obtained directly from the concentration versus time curve.
Measured: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of VX-984
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Measured: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)
Part A: Minimum Observed Plasma Concentration During Dosing Interval (Cmin) of VX-984
Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve.
Measured: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)
Part A: Area Under the Plasma Concentration Curve From Time Zero to 96 Hours Post Dose AUC(0-96h) of Pegylated Liposomal Doxorubicin
The AUC(0-96h) was estimated by determining the total area under the curve of the concentration versus curve extrapolated from 0 to 96 hours.
Measured: Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days)
Part A: Maximum Observed Plasma Concentration (Cmax0-96h) From Time Zero to 96 Hours Post Dose of Pegylated Liposomal Doxorubicin
Cmax is the maximum observed plasma concentration obtained directly from concentration versus time curve from zero to 96 hours
Measured: Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days)
Part A: Time to Reach Maximum Plasma Concentration From Zero to 96 Hours Post Dose (tmax0-96h) of Pegylated Liposomal Doxorubicin
Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve from zero to 96 hours post dose.
Measured: Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days)
Part A: Number of Participants With Best Overall Response Evaluated by Response Criteria Evaluation (RECIST 1.1)
The best overall response was defined as the number of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to radiological assessments as adjudicated by the IRC from randomization until the first occurrence of progressive disease (PD). CR: Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2015 (estimated)
- Study start29 Feb 2016
- Primary completion19 Oct 2017
- Study completion19 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by EMD Serono Research & Development Institute, 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
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono Research & Development Institute, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02644278
- Sponsor's protocol ID
- MS201926-0001
- Other IDs
- VX15-984-001
- Status last verified
- Jul 2019
- First submitted
- 10 Dec 2015
- Last updated
- 9 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase 1, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-984 in Combination With Chemotherapy in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02644278
- Acronym / sponsor ID
- MS201926-0001
- Conditions
- Advanced Solid Tumor
- Keywords
- VX15-984-001, VX-984, M9831, Advanced Solid Tumor, Pegylated liposomal doxorubicin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- EMD Serono Research & Development Institute, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 29 Feb 2016 (actual)
- Primary completion
- 19 Oct 2017 (actual)
- Study completion
- 19 Oct 2017 (actual)
- First posted
- 31 Dec 2015 (estimated)
- Results
- Posted 9 Sep 2019
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 was to evaluate the safety and tolerability of VX-984 (M9831) administered alone and in combination with pegylated liposomal doxorubicin (PLD), and to determine the maximum tolerated dose (MTD) and preliminary evidence of efficacy of VX-984 in combination with PLD in participants with advanced solid tumors.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| VX-984 120 mg + PLD 40 mg/m^2 | Experimental | Drug: VX-984 120 mg + PLD 40 mg/m^2 |
| VX-984 240 mg + PLD 40 mg/m^2 | Experimental | Drug: VX-984 240 mg + PLD 40 mg/m^2 |
| VX-984 480 mg + PLD 40 mg/m^2 | Experimental | Drug: VX-984 480 mg + PLD 40 mg/m^2 |
| VX-984 720 mg + PLD 40 mg/m^2 | Experimental | Drug: VX-984 720 mg + PLD 40 mg/m^2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Participants (male and female for Part A and female for Part B) were at least 18 year of age.
- Part A Participants with histologically or cytologically confirmed malignant advanced solid tumors, who had progressed on at least 1 prior chemotherapy, and for whom either
- Part B
- Measurable disease according to RECIST criteria (Version 1.1)
- Life expectancy of at least 12 weeks
Key exclusion criteria (16 listed)
- Previous radiotherapy (unless brachytherapy), endocrine therapy, chemotherapy, or exposure to investigational medicinal products during the 4 weeks (6 weeks for nitrosoureas and Mitomycin-C) or 4 drug half-lives before the planned administration of the first dose of study drug, whichever is greater. Previous immunotherapy during the 4 weeks before the planned administration of the first dose of study drug.
- For Part B only:
- Unresolved toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater from previous anti-cancer therapy or radiotherapy
- History of spinal cord compression or brain metastases, unless asymptomatic, treated, stable, and not requiring treatment with steroids for at least 4 weeks before the planned administration of the first dose of study drug. Any history of leptomeningeal metastases.
- Female participants who was pregnant or lactating at Screening, or planned to become pregnant while on study or within 6 months after the last dose of study drug
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 |
|---|---|---|
| VX-984 120 mg + PLD 40 mg/m^2Also: M9831Participants received VX-984 orally 120 milligram (mg) orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m^2. | Drug | VX-984 120 mg + PLD 40 mg/m^2 |
| VX-984 240 mg + PLD 40 mg/m^2Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m^2. | Drug | VX-984 240 mg + PLD 40 mg/m^2 |
| VX-984 480 mg + PLD 40 mg/m^2Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m^2. | Drug | VX-984 480 mg + PLD 40 mg/m^2 |
| VX-984 720 mg + PLD 40 mg/m^2Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m^2. | Drug | VX-984 720 mg + PLD 40 mg/m^2 |
Primary outcome
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-Emergent adverse events (TEAEs) were defined as AEs that were reported or worsened on or after the start of study drug dosing through the 28-day Safety Follow-up visit. TEAEs included both Serious TEAEs and non-serious TEAEs.
Part A: Number of Participants Who Experienced Dose Limiting Toxicity (DLT)
Time frame: Cycle 1 (each cycle is 28 days)
DLT was defined using National cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 as any of the following toxicities: Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (>=) 3 febrile neutropenia; Grade 4 or Grade 3 thrombocytopenia with bleeding. Grade >= 3 uncontrolled nausea/vomiting and/or diarrhea despite adequate and optimal treatment and Grade >= 3 any non- hematological adverse event (AE), except the aforementioned gastrointestinal events and alopecia.
Part A: Number of Participants With Toxicity Grade 3 or Higher in Laboratory Abnormalities
Time frame: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
The laboratory measurements included hematology and serum chemistry. It had been graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 into Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Life-threatening) and Grade 5 = death. Participants with grade 3 or higher were reported.
Part A: Maximum Tolerated Dose (MTD) of VX-984 in Combination With Pegylated Liposomal Doxorubicin (PLD)
Time frame: Up to Cycle 1 Day 28 (each cycle is 28 days)
The MTD was defined as the combination dose associated with the highest probability that Dose limiting toxicity (DLT) events will occur in 16.6 percent to less than 33.3 percent participants as the combination dose that not exceeded the overdose criterion (more than 25 percent probability that DLT events occurred less than or equal to (>=) 33 percent of participants. DLT was defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0.
Part A: Number of Participants With Clinical Significant Abnormalities in Vital Signs
Time frame: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
Vital signs assessment included blood pressure, pulse rate and body temperature. Clinical significance was determined by the investigator. Number of participants with clinical significant abnormalities in vital Signs reported here.
Part A: Number of Participants With Clinical Significant Abnormalities Echocardiograms
Time frame: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
Echocardiogram is a graphic outline of the heart's movement. Clinical significance was determined by the investigator. Number of participants with clinical significant abnormalities in Echocardiograms reported here.
Part A: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram(ECG) Parameters
Time frame: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks
ECG parameters included heart rate, pulse rate, QRS,QT, RR, QTcB and QTcF. Clinical significance was determined by the investigator. Number of participants with clinical significant abnormalities in ECG parameters reported here.
8 secondary outcomes
Part A: Area Under Plasma Concentration (AUC) During a Dosing Interval of VX-984
Time frame: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)
Part A: Maximum Observed Plasma Concentration (Cmax) of VX-984
Time frame: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of VX-984
Time frame: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)
Part A: Minimum Observed Plasma Concentration During Dosing Interval (Cmin) of VX-984
Time frame: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)
Part A: Area Under the Plasma Concentration Curve From Time Zero to 96 Hours Post Dose AUC(0-96h) of Pegylated Liposomal Doxorubicin
Time frame: Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days)
Part A: Maximum Observed Plasma Concentration (Cmax0-96h) From Time Zero to 96 Hours Post Dose of Pegylated Liposomal Doxorubicin
Time frame: Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days)
Part A: Time to Reach Maximum Plasma Concentration From Zero to 96 Hours Post Dose (tmax0-96h) of Pegylated Liposomal Doxorubicin
Time frame: Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days)
Part A: Number of Participants With Best Overall Response Evaluated by Response Criteria Evaluation (RECIST 1.1)
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
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.
Medical Responsible study director
EMD Serono Research & Development Institute, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
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 VX-984 120 mg + PLD 40 mg/m^2, VX-984 240 mg + PLD 40 mg/m^2 and VX-984 480 mg + PLD 40 mg/m^2 in people with Advanced Solid Tumor, run by EMD Serono Research & Development Institute, Inc. 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 11 inclusion and 16 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 Sep 2019. 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?
Yes. Results are posted in the registry (first posted 9 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs (time frame: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks). The study lists 7 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 9 Sep 2019.