Advanced CancersPhase 2NCT02873975
A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency
A Phase 2 study testing LY2606368 in people with Advanced Cancers, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
This research study is studying a checkpoint kinase 1 (CHK1) inhibitor as a possible treatment for advanced solid tumors that harbor genetic alterations in the homologous repair (HR) pathway, genetic alterations that indicate replication stress, or with CCNE1 amplification. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancers
- What is being tested?
- LY2606368
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Oct 2016to 1 Jul 2021
- Phase
- Phase 2
- 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 must have a pathologically confirmed advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
- Participants must have one of the following (confirmed via targeted NextGeneration sequencing [NGS] using the DFCI/BWH OncoPanel or another CLIA-certified method):
- For the replicative stress cohort: MYC amplification, CCNE1 amplification, Rb loss, FBXW7 mutation, or another genomic abnormality indicative of replicative stress as agreed upon with the principal investigator. OR
- For the HR deficiency cohort: genomic or somatic mutation in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, the Fanconi anemia pathway genes, or another genomic or somatic mutation in a known HR gene as agreed upon with the principal investigator.
- For the CCNE1 cohort: CCNE1 amplification of 6-fold or greater. Patients with borderline amplification levels may be considered following approval from the overall principal investigator.
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam.
Show all 19Show fewer
- Age ≥ 18 years.
- ECOG performance status < 2
- Participants must have adequate organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1.5 K/uL
- Platelet count ≥ 100 K/uL
- Hemoglobin ≥ 9 g/dL (with or without transfusion support)
- Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN, unless liver metastases are present and then ≤ 5 × institutional ULN is acceptable
- Serum creatinine ≤ 1.5 × institutional ULN
- Participants enrolling to the HR or replicative stress cohorts during Stage 1 must have disease that is amenable to biopsy and be willing to undergo a pre-treatment tumor biopsy.
- The potential effects of LY2606368 use during pregnancy and lactation are not known. Nonclinical studies of LY2606368 on pregnancy and fetal development have not been performed. To minimize any potential risks, men and women with reproductive potential should use medically approved contraceptive precautions during treatment and for 3 months following the last dose of LY2606368. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 3 months after completion of LY2606368 administration.
- Ability to understand and the willingness to sign a written informed consent document.
- QTcF value of ≤ 470 msec on screening electrocardiogram (EKG)
Who cannot join
- Participants who have had chemotherapy, other investigational or biologic therapy, major surgery, or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the planned first dose of LY2606368 therapy.
- Participants who have not recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to the study.
- Participants who have received prior treatment with a CHK1 inhibitor.
- Participants who have received prior radiation therapy to > 25% of the bone marrow.
- Participants with known untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with a history of brain metastases that have been treated, are no longer taking corticosteroids, and have been stable on imaging for at least one month following the end of treatment are permitted.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to LY2606368.
Show all 11Show fewer
- Participants with a personal or family history of long QT syndrome.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, NYHA Class III/IV heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction within 3 months of enrollment, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding females. The potential effects of LY2606368 use during pregnancy and breastfeeding are not known and LY2606368 has the potential for teratogenic or abortifacient effects.
- Known HIV-positive participants are ineligible because these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in HIV-positive participants when indicated.
- Participants enrolling to the HR or replicative stress cohort during Stage 1 may not be on anticoagulant therapy unless the treating investigator has deemed it safe to temporarily hold to facilitate the pre-treatment tumor biopsy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase II Study of the CHK1 Inhibitor LY2606368 in Patients With Advanced Solid Tumors Exhibiting Replicative Stress or Homologous Recombination Repair Deficiency
This research study is studying a checkpoint kinase 1 (CHK1) inhibitor as a possible treatment for advanced solid tumors that harbor genetic alterations in the homologous repair (HR) pathway, genetic alterations that indicate replication stress, or with CCNE1 amplification.
Read the detailed description
This is an open label, phase II, two-arm study exploring the anti-tumor activity of the CHK1 inhibitor prexasertib (LY2606368) in patients with advanced solid tumors exhibiting one of the following:
- Replicative stress, including MYC amplification, CCNE1 amplification, Rb loss, or an FBXW7 mutation
- An HR deficiency, including tumors with genomic or somatic mutations of BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, or the Fanconi anemia pathway genes
- A CCNE1 amplification
- Conditions
- Advanced Cancers
- Being tested
- LY2606368
- Keywords
- Advanced Cancers, Solid tumors, MYC amplification, CCNE1 amplification, Rb loss, FBXW7 mutation, BRCA1 mutation, BRCA2 mutation, PALB2 mutation, RAD51C mutation, RAD51D mutation, ATR mutation, ATM mutation, CHK2 mutation, Fanconi anemia
- Medical subject headings
- Fanconi Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY2606368Drug
Also called Prexasertib
| Study group | Role | What they receive |
|---|---|---|
| Homologous Repair (HR) Deficiency Cohort | Experimental | Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour. Receives: Drug: LY2606368 |
| Replicative Stress Cohort | Experimental | Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour. Receives: Drug: LY2606368 |
| CCNE1 Amplification Cohort | Experimental | Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour. Receives: Drug: LY2606368 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Rate at 4 Month
Progression-Free Rate defines as the percentage of participants progression-free at 4 months in all arms, by RECIST 1.1 criteria. Progression-free rate will be estimated as binomial proportion and overall survival and progression-free survival estimates and curves will be generated using the Kaplan-Meier method.
Measured: at 4 month
Secondary outcomes (3)
Incidence of Grade 4 Treatment-Related Toxicity
All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEvE as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.
Measured: Assessed cycle 1 at day 1, 8, 15 and 22, and cycle 2 at day 1 and 15, from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 55 day (range 6 - 539 days).
Objective Response Rate
The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Measured: Disease was evaluated radiologically at baseline and on treatment; Treatment continued until disease progression or unacceptable toxicity. Median treatment duration for this study cohort was 55 day (range 6 - 539 days).
Median Overall Survival (OS)
OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Measured: Participants were followed long-term for survival months from the end of treatment until death or lost to follow-up. Median (range) follow-up was 133 days (15-862 days) in this study cohort.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2016 (estimated)
- Study start12 Oct 2016
- Primary completion30 Sep 2020
- Study completion1 Jul 2021
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 CancersStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Geoffrey Shapiro, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02873975
- Sponsor's protocol ID
- 16-281
- Status last verified
- Sep 2022
- First submitted
- 17 Aug 2016
- Last updated
- 21 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the CHK1 Inhibitor LY2606368 in Patients With Advanced Solid Tumors Exhibiting Replicative Stress or Homologous Recombination Repair Deficiency
- ClinicalTrials.gov ID
- NCT02873975
- Acronym / sponsor ID
- 16-281
- Conditions
- Advanced Cancers
- Keywords
- Advanced Cancers, Solid tumors, MYC amplification, CCNE1 amplification, Rb loss, FBXW7 mutation, BRCA1 mutation, BRCA2 mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- 12 Oct 2016 (actual)
- Primary completion
- 30 Sep 2020 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 22 Aug 2016 (estimated)
- Results
- Posted 9 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a checkpoint kinase 1 (CHK1) inhibitor as a possible treatment for advanced solid tumors that harbor genetic alterations in the homologous repair (HR) pathway, genetic alterations that indicate replication stress, or with CCNE1 amplification.
Detailed description
This is an open label, phase II, two-arm study exploring the anti-tumor activity of the CHK1 inhibitor prexasertib (LY2606368) in patients with advanced solid tumors exhibiting one of the following:
- Replicative stress, including MYC amplification, CCNE1 amplification, Rb loss, or an FBXW7 mutation
- An HR deficiency, including tumors with genomic or somatic mutations of BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, or the Fanconi anemia pathway genes
- A CCNE1 amplification
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Homologous Repair (HR) Deficiency Cohort | Experimental | Drug: LY2606368Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour. |
| Replicative Stress Cohort | Experimental | Drug: LY2606368Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour. |
| CCNE1 Amplification Cohort | Experimental | Drug: LY2606368Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participants must have a pathologically confirmed advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
- Participants must have one of the following (confirmed via targeted NextGeneration sequencing [NGS] using the DFCI/BWH OncoPanel or another CLIA-certified method):
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam.
- Age ≥ 18 years.
- ECOG performance status < 2
Key exclusion criteria (11 listed)
- Participants who have had chemotherapy, other investigational or biologic therapy, major surgery, or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the planned first dose of LY2606368 therapy.
- Participants who have not recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to the study.
- Participants who have received prior treatment with a CHK1 inhibitor.
- Participants who have received prior radiation therapy to > 25% of the bone marrow.
- Participants with known untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with a history of brain metastases that have been treated, are no longer taking corticosteroids, and have been stable on imaging for at least one month following the end of treatment are permitted.
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 |
|---|---|---|
| LY2606368Also: Prexasertib | Drug | CCNE1 Amplification Cohort, Homologous Repair (HR) Deficiency Cohort, Replicative Stress Cohort |
Primary outcome
Progression-Free Rate at 4 Month
Time frame: at 4 month
Progression-Free Rate defines as the percentage of participants progression-free at 4 months in all arms, by RECIST 1.1 criteria. Progression-free rate will be estimated as binomial proportion and overall survival and progression-free survival estimates and curves will be generated using the Kaplan-Meier method.
3 secondary outcomes
Incidence of Grade 4 Treatment-Related Toxicity
Time frame: Assessed cycle 1 at day 1, 8, 15 and 22, and cycle 2 at day 1 and 15, from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 55 day (range 6 - 539 days).
Objective Response Rate
Time frame: Disease was evaluated radiologically at baseline and on treatment; Treatment continued until disease progression or unacceptable toxicity. Median treatment duration for this study cohort was 55 day (range 6 - 539 days).
Median Overall Survival (OS)
Time frame: Participants were followed long-term for survival months from the end of treatment until death or lost to follow-up. Median (range) follow-up was 133 days (15-862 days) in this study cohort.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Advanced Cancers
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
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.
Geoffrey Shapiro, MD, PhD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LY2606368 in people with Advanced Cancers, run by Dana-Farber Cancer Institute at 1 site 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 19 inclusion and 11 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 21 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Feb 2022). 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?
Progression-Free Rate at 4 Month (time frame: at 4 month). 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 21 Oct 2022.