Epithelial Ovarian CancerPhase 1NCT02943317
Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of Defactinib in Combination With Avelumab in Epithelial Ovarian Cancer
A Phase 1 study testing Part A - VS-6063 and Part A - Avelumab in people with Epithelial Ovarian Cancer, run by Verastem, Inc. at 5 sites in United States.
Trial summary
This is a Phase 1/1b, open-label, multicenter, dose-escalation and dose expansion trial to evaluate the safety, efficacy, PK and PD of defactinib (VS-6063) in combination with avelumab in epithelial ovarian cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Epithelial Ovarian Cancer
- What is being tested?
- Part A - VS-6063 and Part A - Avelumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 5 sitesUnited States
- Study dates
- Oct 2016to 28 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to provide signed and dated informed consent before initiation of any study procedures.
- Willing and able to participate in the trial and comply with all trial requirements.
- Female subject aged ≥ 18 years.
- Histologically or cytologically-confirmed recurrent or resistant (progression within 6 months following the last administered platinum based therapy or progression after subsequent therapy in previously relapsed subjects), stage III-IV epithelial ovarian, fallopian tube or peritoneal cancer subjects (according to American Joint Committee on Cancer/Union for International Cancer Control TNM and International Federation of Gynecology and Obstetrics Staging System, 7th edition) whose disease has progressed following adjuvant therapy or therapy for metastatic disease.
- Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
- Confirmed availability of archived FFPE tumor tissue block, or a minimum of 15 slides. If archived FFPE tissue is not available, then fresh tumor sample may be obtained in accordance with local institutional practice for tumor biopsies.
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- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1, measured within 72 hours before the start of treatment.
- Predicted life expectancy of ≥ 3 months.
- Adequate renal function with normal serum creatinine, or if creatinine above or below institutional normal range, a calculated glomerular filtration rate of ≥ 50 mL/min/1.73m2 (e.g., as calculated by the Cockcroft Gault formula) using actual body weight; if subject has body mass index > 30 kg/m2, lean body weight must be used.
- Adequate hepatic function (total bilirubin ≤ 1.5 × upper limit of normal [ULN] for the institution; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN.
- Adequate bone marrow function (hemoglobin [Hb] ≥ 9.0 g/dL [subjects may be transfused to Hb ≥ 9.0 g/dL]; platelets ≥ 100 × 109cells/L; absolute neutrophil count [ANC] ≥ 1.5 × 109 cells/L without the use of hematopoietic growth factors).
- Corrected QT interval (QTc) < 470 msec (as calculated by the Fridericia correction formula [QTcF]).
- Negative pregnancy test within 72 hours prior to the first dose of protocol therapy for women of childbearing potential. Must be willing to use effective contraception for 30 days before the first study drug administration, for the duration of trial participation and at least for 60 days after stopping trial participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician must be informed immediately.
Who cannot join
- Concurrent anticancer treatment, major surgery or use of any investigational drug within 28 days or 5 half-lives, whichever is shorter, before the start of trial treatment; palliative radiation therapy is allowed if > 21 days before planned first dose of study drugs and any toxicity is ≤ Grade 1.
- Concurrent systemic therapy with immunosuppressive agents; use of hormonal agents within 7 days before the start of trial treatment. Note: subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab. Subjects receiving immunosuppressive agents (such as corticosteroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily). Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
- Prior treatment with a drug of the focal adhesion kinase (FAK) inhibitor class.
- Prior therapy with specific antibody/drug targeting immune or coregulatory or costimulatory proteins (such as checkpoints e.g., PD-1 or PD L1, 4-1BB, OX40 or CTLA-4 antibodies).
- Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation.
- Uncontrolled brain metastases (Stable brain metastases either treated or being treated with a stable dose of anticonvulsants, with no dose change within 28 days before enrollment, will be allowed.).
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- Women who are pregnant or breastfeeding.
- Any evidence of serious active infections; any infections being treated must complete antibiotic therapy at least 7 days before planned first dose.
- Active or history of any autoimmune disease (subjects with diabetes type 1, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible).
- Current acute or chronic colitis, inflammatory bowel disease, pneumonitis or pulmonary fibrosis.
- Known severe hypersensitivity reactions to monoclonal antibodies; any history of anaphylaxis or uncontrolled asthma.
- Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months before study treatment, New York Heart Association Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease or cardiac amyloidosis.
- Known history of stroke or cerebrovascular accident within 6 months before enrollment.
- Known infection with human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) (testing not required).
- Active hepatitis B or C (testing required).
- Known history of Gilbert's Syndrome.
- Other uncontrolled or poorly controlled intercurrent illness (e.g., involving the renal, hepatic, neurologic, dermatologic, pulmonary, endocrine systems) or psychiatric illness/social situations that would limit compliance with study requirements, place the subject at undue risk or confound interpretation of safety or other data.
- Gastrointestinal (GI) condition that could interfere with the swallowing or absorption of defactinib.
- History of upper GI bleeding, ulceration or perforation within 6 months before the first dose of defactinib.
- Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
- Previous malignant disease other than the target malignancy to be investigated in this trial within the last 3 years, with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ. Any prior cancer must not be getting active treatment and must be in continuous complete remission for at least 3 years.
- Persisting toxicity related to prior therapy > Grade 1 National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 (NCI-CTCAE v4.03); however, sensory neuropathy ≤ Grade 2 is acceptable.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Dana Farber Cancer Instiyute
Boston, Massachusetts, 02215
Mary Crowley Cancer Research Centers
Dallas, Texas, 75251
Sarah Cannon Research Institute at Tennessee Oncology
Nashville, Tennessee, 37203
Stephenson Cancer Center (University of Oklahoma)
Oklahoma City, Oklahoma, 73104
Florida Cancer Specialists & Research Institute (FCS)
Sarasota, Florida, 34232
About this study
Official title: A Phase 1/1b Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of Defactinib in Combination With Avelumab in Epithelial Ovarian Cancer
This is a Phase 1/1b, open-label, multicenter, dose-escalation and dose expansion trial to evaluate the safety, efficacy, PK and PD of defactinib (VS-6063) in combination with avelumab in epithelial ovarian cancer.
Read the detailed description
The study is comprised of 2 sequential parts: Part A (Dose Escalation of VS-6063) and Part B (Expansion).
In Part A (Dose Escalation), approximately 18 subjects will receive avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15) and oral defactinib twice-daily (BID) continuously starting on Day 1 of Cycle 1. Subject enrollment will proceed according to a standard 3+3 design. In the absence of dose-limiting toxicity (DLT), each subject will receive the study drug regimen for a minimum of 28 days (Cycle 1) and may continue to receive additional cycles of study treatment until disease progression has been documented or unacceptable toxicity or other treatment discontinuation criteria have been met. All subjects in a cohort must have completed at least 1 cycle of dosing before dose escalation involving new subjects entered into the next dose cohort can occur. Based on the safety and PK data obtained in the dose escalation portion of the study, the RP2D of the combination will be determined.
In Part B (Expansion), approximately 80 subjects will be enrolled and will receive avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15) and oral defactinib at the RP2D dose continuously starting on Day 1 of Cycle 1.
- Conditions
- Epithelial Ovarian Cancer
- Being tested
- Part A - VS-6063, Part A - Avelumab
- Medical subject headings
- Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part A - VS-6063Drug
Also called Defactinib
Part A - Oral VS-6063 (defactinib) twice-daily (BID) continuously starting on Day 1 of Cycle 1.
Part A - AvelumabDrug
Part A - avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15).
| Study group | Role | What they receive |
|---|---|---|
| Part A: VS-6063 | Experimental | Part A - Oral VS-6063 (defactinib) twice-daily (BID) continuously starting on Day 1 of Cycle 1. Receives: Drug: Part A - VS-6063 |
| Part A: Avelumab | Experimental | Part A - avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15). Receives: Drug: Part A - Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants taking defactinib in combination with avelumab with Adverse Events as a Measure of Safety and Tolerability
Measured: Up to 90 days after last dose
maximum tolerated dose (MTD) of defactinib in combination with avelumab (Part A)
Measured: From start of treatment to end of Cycle 1 (28 days)
best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Part B)
Measured: From start of treatment, assessed up to 52 weeks
Secondary outcomes (7)
time to treatment response disease control
Measured: 12, 24, 36, and 52 weeks
best overall response according to immune-related response evaluation criteria in solid tumors (irRECIST)
Measured: From start of treatment, assessed up to 52 weeks
immune related progression-free survival (irPFS) time according to irRECIST and RECIST v1.1
Measured: From start of treatment until first documented progression or death, whichever comes first, assessed up to 52 weeks
progression-free survival (PFS) time according to irRECIST and RECIST v1.1
Measured: From start of treatment until first documented progression or death, whichever comes first, assessed up to 52 weeks
overall Survival (OS)
Measured: From start of treatment until death, assessed up to 52 weeks
duration of response (DOR) according to irRECIST and RECIST v1.1
Measured: From start of treatment until first documented progression, assessed up to 52 weeks
plasma concentration of avelumab and defactinib
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2016 (estimated)
- Study startOct 2016
- Primary completion28 Aug 2018
- Study completion28 Dec 2018
Why it stopped: The study was terminated upon completion of escalation phase, prior to opening expansion cohorts
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epithelial Ovarian 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 98 participants (estimated)
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
- NCT02943317
- Sponsor's protocol ID
- VS-6063-107
- Status last verified
- Jul 2018
- First submitted
- 17 Oct 2016
- Last updated
- 30 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of Defactinib in Combination With Avelumab in Epithelial Ovarian Cancer
- ClinicalTrials.gov ID
- NCT02943317
- Acronym / sponsor ID
- VS-6063-107
- Conditions
- Epithelial Ovarian Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated upon completion of escalation phase, prior to opening expansion cohorts
- Enrolment
- 98 participants (estimated)
- Lead sponsor
- Verastem, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2016
- Primary completion
- 28 Aug 2018 (actual)
- Study completion
- 28 Dec 2018 (actual)
- First posted
- 24 Oct 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.
This is a Phase 1/1b, open-label, multicenter, dose-escalation and dose expansion trial to evaluate the safety, efficacy, PK and PD of defactinib (VS-6063) in combination with avelumab in epithelial ovarian cancer.
Detailed description
The study is comprised of 2 sequential parts: Part A (Dose Escalation of VS-6063) and Part B (Expansion).
In Part A (Dose Escalation), approximately 18 subjects will receive avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15) and oral defactinib twice-daily (BID) continuously starting on Day 1 of Cycle 1. Subject enrollment will proceed according to a standard 3+3 design. In the absence of dose-limiting toxicity (DLT), each subject will receive the study drug regimen for a minimum of 28 days (Cycle 1) and may continue to receive additional cycles of study treatment until disease progression has been documented or unacceptable toxicity or other treatment discontinuation criteria have been met. All subjects in a cohort must have completed at least 1 cycle of dosing before dose escalation involving new subjects entered into the next dose cohort can occur. Based on the safety and PK data obtained in the dose escalation portion of the study, the RP2D of the combination will be determined.
In Part B (Expansion), approximately 80 subjects will be enrolled and will receive avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15) and oral defactinib at the RP2D dose continuously starting on Day 1 of Cycle 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: VS-6063 | Experimental | Drug: Part A - VS-6063Part A - Oral VS-6063 (defactinib) twice-daily (BID) continuously starting on Day 1 of Cycle 1. |
| Part A: Avelumab | Experimental | Drug: Part A - AvelumabPart A - avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Able to provide signed and dated informed consent before initiation of any study procedures.
- Willing and able to participate in the trial and comply with all trial requirements.
- Female subject aged ≥ 18 years.
- Histologically or cytologically-confirmed recurrent or resistant (progression within 6 months following the last administered platinum based therapy or progression after subsequent therapy in previously relapsed subjects), stage III-IV epithelial ovarian, fallopian tube or peritoneal cancer subjects (according to American Joint Committee on Cancer/Union for International Cancer Control TNM and International Federation of Gynecology and Obstetrics Staging System, 7th edition) whose disease has progressed following adjuvant therapy or therapy for metastatic disease.
- Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
Key exclusion criteria (22 listed)
- Concurrent anticancer treatment, major surgery or use of any investigational drug within 28 days or 5 half-lives, whichever is shorter, before the start of trial treatment; palliative radiation therapy is allowed if > 21 days before planned first dose of study drugs and any toxicity is ≤ Grade 1.
- Concurrent systemic therapy with immunosuppressive agents; use of hormonal agents within 7 days before the start of trial treatment. Note: subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab. Subjects receiving immunosuppressive agents (such as corticosteroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily). Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
- Prior treatment with a drug of the focal adhesion kinase (FAK) inhibitor class.
- Prior therapy with specific antibody/drug targeting immune or coregulatory or costimulatory proteins (such as checkpoints e.g., PD-1 or PD L1, 4-1BB, OX40 or CTLA-4 antibodies).
- Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation.
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 A - VS-6063Also: DefactinibPart A - Oral VS-6063 (defactinib) twice-daily (BID) continuously starting on Day 1 of Cycle 1. | Drug | Part A: VS-6063 |
| Part A - AvelumabPart A - avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15). | Drug | Part A: Avelumab |
Primary outcome
Number of Participants taking defactinib in combination with avelumab with Adverse Events as a Measure of Safety and Tolerability
Time frame: Up to 90 days after last dose
maximum tolerated dose (MTD) of defactinib in combination with avelumab (Part A)
Time frame: From start of treatment to end of Cycle 1 (28 days)
best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Part B)
Time frame: From start of treatment, assessed up to 52 weeks
7 secondary outcomes
time to treatment response disease control
Time frame: 12, 24, 36, and 52 weeks
best overall response according to immune-related response evaluation criteria in solid tumors (irRECIST)
Time frame: From start of treatment, assessed up to 52 weeks
immune related progression-free survival (irPFS) time according to irRECIST and RECIST v1.1
Time frame: From start of treatment until first documented progression or death, whichever comes first, assessed up to 52 weeks
progression-free survival (PFS) time according to irRECIST and RECIST v1.1
Time frame: From start of treatment until first documented progression or death, whichever comes first, assessed up to 52 weeks
overall Survival (OS)
Time frame: From start of treatment until death, assessed up to 52 weeks
duration of response (DOR) according to irRECIST and RECIST v1.1
Time frame: From start of treatment until first documented progression, assessed up to 52 weeks
plasma concentration of avelumab and defactinib
Time frame: 15 days
Results and safety
The study was stopped early (reason given: The study was terminated upon completion of escalation phase, prior to opening expansion cohorts). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2019.
- Individual participant dataSharing planned: Undecided
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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.
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 Part A - VS-6063 and Part A - Avelumab in people with Epithelial Ovarian Cancer, run by Verastem, 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 13 inclusion and 22 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 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 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?
The study was stopped early (reason given: The study was terminated upon completion of escalation phase, prior to opening expansion cohorts). 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?
Number of Participants taking defactinib in combination with avelumab with Adverse Events as a Measure of Safety and Tolerability (time frame: Up to 90 days after last dose). The study lists 3 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 Apr 2019.