Pancreatic CancerPhase 1NCT02651727
Ph 1 Study of VS-4718, a FAK Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Advanced Cancer Subjects
A Phase 1 study testing Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine, Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine and Part A- VS-4718, nab-paclitaxel, gemcitabine in people with Pancreatic Cancer, run by Verastem, Inc. at 2 sites in United States.
Trial summary
The purpose of this study is to evaluate increasing dose levels of VS-4718 administered in combination with gemcitabine and nab-paclitaxel in subjects with advanced cancer and to determine a recommended Phase 2 dose (RP2D) for further development of this combination in subjects with untreated advanced pancreatic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine, Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine and Part A- VS-4718, nab-paclitaxel, gemcitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2015to Jan 2017
- 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
- Age ≥ 18 years
- Histologically or cytologically confirmed diagnosis of an advanced nonhematological malignancy (Part A) or advanced pancreatic adenocarcinoma (Part B) that is not surgically resectable
- Eligible for treatment with nab-paclitaxel and gemcitabine on Days 1, 8, and 15 in 28-day cycles as standard therapy
- Evaluable or measurable disease, as assessed by RECIST v1.1
- ECOG performance status of ≤ 1
- Adequate renal function (creatinine ≤ 1.5×ULN [upper limit of normal]) or glomerular filtration rate of ≥ 60 mL/min
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- Adequate hepatic function (total bilirubin ≤ 1.5×ULN for the institution; aspartate transaminase and alanine transaminase ≤ 2.5×ULN, or ≤ 5×ULN if due to liver involvement by tumor; albumin ≥ 3 g/dL)
- Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; unsupported platelets ≥ 100×109 cells/L; absolute neutrophil count [ANC] ≥ 1.5×109 cells/L without the use of hematopoietic growth factors)
- Corrected QT interval (QTc) < 470 ms
- Willing and able to participate in the trial and comply with all trial requirements
Who cannot join
- Gastrointestinal (GI) condition that could interfere with the swallowing or absorption of study medication
- Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases).
- History of upper gastrointestinal bleeding, ulceration, or perforation within 6 months prior to the first dose of protocol therapy
- Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of protocol therapy.
- Part B only: Prior therapy (including investigational agents) for pancreatic cancer
- Chemotherapy or radiotherapy within 14 days prior to first dose of protocol therapy
- Active treatment for a secondary malignancy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Gettysburg Cancer Center
Gettysburg, Pennsylvania, 17325
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase 1 Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Subjects With Advanced Cancer
The purpose of this study is to evaluate increasing dose levels of VS-4718 administered in combination with gemcitabine and nab-paclitaxel in subjects with advanced cancer and to determine a recommended Phase 2 dose (RP2D) for further development of this combination in subjects with untreated advanced pancreatic cancer.
Read the detailed description
The study is comprised of 2 sequential parts: Part A (Dose Escalation of VS-4718) in subjects with advanced cancer and Part B (Expansion) in subjects with untreated advanced pancreatic cancer.
Up to 60 evaluable subjects (i.e., subjects who complete at least 1 cycle (28 days) of therapy) will be enrolled, assuming that:
- Part A: The maximum sample size will be 6 subjects up to 4 dose levels (exclusive of replacement subjects). However, additional subjects may be added if exploration of intermediate dose level(s) of VS 4718 is warranted. The starting dose of VS-4718 will be 200mg BID.
- Part B: Up to 36 additional subjects may be enrolled at the RP2D. These subjects will be randomized at a 1:1 ratio to 1 of 2 treatment cohorts:
- Cohort 1: IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1
- Cohort 2: IV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3
- Conditions
- Pancreatic Cancer
- Being tested
- Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine, Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine, Part A- VS-4718, nab-paclitaxel, gemcitabine
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabineDrug
IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1
Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabineDrug
IV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3
Part A- VS-4718, nab-paclitaxel, gemcitabineDrug
Part A- intravenous (IV) treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 twice-daily (BID) continuously starting on Cycle 1 Day 2. The starting dose of VS-4718 will be 200 mg BID.
| Study group | Role | What they receive |
|---|---|---|
| Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine | Experimental | Part B, Cohort 1- IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1 Receives: Drug: Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine |
| Part B, Cohort 2- VS-4718, nab-paclitaxel, gemcitabine | Experimental | Part B, Cohort 2- IV treatment for the first 2 cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15), followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3 Receives: Drug: Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine |
| Part A- VS-4718, nab-paclitaxel, gemcitabine | Experimental | Part A- intravenous (IV) treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 twice-daily (BID) continuously starting on Cycle 1 Day 2. The starting dose of VS-4718 will be 200 mg BID. Receives: Drug: Part A- VS-4718, nab-paclitaxel, gemcitabine |
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-4718 in combination with gemcitabine and nab-paclitaxel
Measured: 6 months
Secondary outcomes (8)
Progression Free Survival
Measured: From the date of first treatment to the date of progression including death from any cause, expected average at least 5 months
Response rate (RR)
RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.
Measured: Every 8 weeks from baseline through the end of treatment, an expected average of 5 months]
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Clearance
Measured: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Plasma concentration
Measured: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Area under the plasma concentration versus time curve (AUC)
Measured: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Maximum observed plasma concentration (Cmax)
Measured: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Time to reach maximum observed concentration (Tmax)
Measured: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Half life (T1/2)
Measured: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2016 (estimated)
- Study startSep 2015
- Primary completionJan 2017
- Study completionJan 2017
Why it stopped: the company's decision to de-prioritize 4718 development
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Verastem, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hagop Youssoufian, MD, Study chair, Verastem, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02651727
- Sponsor's protocol ID
- VS-4718-103
- Status last verified
- Jan 2017
- First submitted
- 6 Jan 2016
- Last updated
- 27 Jul 2017
- 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 27 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Subjects With Advanced Cancer
- ClinicalTrials.gov ID
- NCT02651727
- Acronym / sponsor ID
- VS-4718-103
- Conditions
- Pancreatic Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: the company's decision to de-prioritize 4718 development
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Verastem, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2015
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 11 Jan 2016 (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 increasing dose levels of VS-4718 administered in combination with gemcitabine and nab-paclitaxel in subjects with advanced cancer and to determine a recommended Phase 2 dose (RP2D) for further development of this combination in subjects with untreated advanced pancreatic cancer.
Detailed description
The study is comprised of 2 sequential parts: Part A (Dose Escalation of VS-4718) in subjects with advanced cancer and Part B (Expansion) in subjects with untreated advanced pancreatic cancer.
Up to 60 evaluable subjects (i.e., subjects who complete at least 1 cycle (28 days) of therapy) will be enrolled, assuming that:
- Part A: The maximum sample size will be 6 subjects up to 4 dose levels (exclusive of replacement subjects). However, additional subjects may be added if exploration of intermediate dose level(s) of VS 4718 is warranted. The starting dose of VS-4718 will be 200mg BID.
- Part B: Up to 36 additional subjects may be enrolled at the RP2D. These subjects will be randomized at a 1:1 ratio to 1 of 2 treatment cohorts:
- Cohort 1: IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1
- Cohort 2: IV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine | Experimental | Drug: Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabinePart B, Cohort 1- IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1 |
| Part B, Cohort 2- VS-4718, nab-paclitaxel, gemcitabine | Experimental | Drug: Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabinePart B, Cohort 2- IV treatment for the first 2 cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15), followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3 |
| Part A- VS-4718, nab-paclitaxel, gemcitabine | Experimental | Drug: Part A- VS-4718, nab-paclitaxel, gemcitabinePart A- intravenous (IV) treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 twice-daily (BID) continuously starting on Cycle 1 Day 2. The starting dose of VS-4718 will be 200 mg BID. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 18 years
- Histologically or cytologically confirmed diagnosis of an advanced nonhematological malignancy (Part A) or advanced pancreatic adenocarcinoma (Part B) that is not surgically resectable
- Eligible for treatment with nab-paclitaxel and gemcitabine on Days 1, 8, and 15 in 28-day cycles as standard therapy
- Evaluable or measurable disease, as assessed by RECIST v1.1
- ECOG performance status of ≤ 1
Key exclusion criteria (7 listed)
- Gastrointestinal (GI) condition that could interfere with the swallowing or absorption of study medication
- Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases).
- History of upper gastrointestinal bleeding, ulceration, or perforation within 6 months prior to the first dose of protocol therapy
- Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of protocol therapy.
- Part B only: Prior therapy (including investigational agents) for pancreatic cancer
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 |
|---|---|---|
| Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabineIV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1 | Drug | Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine |
| Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabineIV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3 | Drug | Part B, Cohort 2- VS-4718, nab-paclitaxel, gemcitabine |
| Part A- VS-4718, nab-paclitaxel, gemcitabinePart A- intravenous (IV) treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 twice-daily (BID) continuously starting on Cycle 1 Day 2. The starting dose of VS-4718 will be 200 mg BID. | Drug | Part A- VS-4718, nab-paclitaxel, gemcitabine |
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-4718 in combination with gemcitabine and nab-paclitaxel
8 secondary outcomes
Progression Free Survival
Time frame: From the date of first treatment to the date of progression including death from any cause, expected average at least 5 months
Response rate (RR)
Time frame: Every 8 weeks from baseline through the end of treatment, an expected average of 5 months]
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Clearance
Time frame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Plasma concentration
Time frame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Area under the plasma concentration versus time curve (AUC)
Time frame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Maximum observed plasma concentration (Cmax)
Time frame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Time to reach maximum observed concentration (Tmax)
Time frame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Half life (T1/2)
Time frame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Results and safety
The study was stopped early (reason given: the company's decision to de-prioritize 4718 development). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2017.
- 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.
Hagop Youssoufian, MD study chair
Verastem, Inc.
2 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 Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine, Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine and Part A- VS-4718, nab-paclitaxel, gemcitabine in people with Pancreatic Cancer, run by Verastem, Inc. at 2 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 10 inclusion and 7 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 27 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 was stopped early (reason given: the company's decision to de-prioritize 4718 development). 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). 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 27 Jul 2017.