Hodgkin DiseasePhase 1NCT00779584
A Dose-escalation Study of MK-8776 (SCH 900776) With and Without Gemcitabine in Participants With Solid Tumors or Lymphoma (MK-8776-002/P05248)
A Phase 1 study testing MK-8776 and Gemcitabine in people with Hodgkin Disease and Lymphoma, Non-Hodgkin, run by Merck Sharp & Dohme LLC.
Trial summary
This study of MK-8776 (SCH 900776) will evaluate its safety and tolerability when given as monotherapy or in combination with gemcitabine to participants with advanced solid tumors or lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin Disease, Lymphoma, Non-Hodgkin, Neoplasms
- What is being tested?
- MK-8776 and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- No sites listed yet
- Study dates
- 17 Oct 2008to 28 May 2011
- 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
- Must have a diagnosis of an advanced solid tumor malignancy or lymphoma (non-Hodgkin's or Hodgkin's lymphoma).
- Must have histological or cytological evidence of malignancy.
- Must have an advanced malignancy, metastatic or unresectable. For Part A of the study, the metastatic or unresectable malignancy should have recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists, or for which they are not candidates for standard therapy. For Parts B and C of the study, participants with advanced tumors for which gemcitabine is considered standard therapy (eg, pancreatic cancer), may be enrolled without having received prior gemcitabine. Standard therapy is defined as therapy that is approved in a particular line of therapy or considered as standard of care based on published peer reviewed data in a specific line of therapy.
- Gemcitabine-naïve participants with tumors known to be responsive to gemcitabine or participants previously treated with gemcitabine who did not progress while on treatment or who are currently still responding to treatment should only be enrolled in cohorts for which gemcitabine doses are >=1000 mg/m². Participants previously treated with gemcitabine, whose disease has progressed wile on treatment, can be enrolled to any part.
- Must be ambulatory with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participants (and/or parent/guardian for participants who otherwise are unable to provide independent consent) must be willing to give written informed consent and able to adhere to dose and visit schedules.
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- Female participants of childbearing potential must have a negative pregnancy test within 7 days of first dose of protocol therapy.
- Female participants of childbearing potential and male participants whose sexual partners are of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of protocol therapy. Acceptable methods of contraception include condoms (male or female) with or without spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation).
- Must have adequate bone marrow reserve as evidenced by a white blood cell (WBC) count >=3,000/ μL, absolute neutrophil count (ANC) >=1,500/μL AND platelet count >=100,000/μL.
- Must have adequate renal function as evidenced by a serum creatinine level <=1.5 x upper limit of normal (ULN) or a calculated creatinine clearance >60 mL/min.
- Participants, except those with known Gilbert's Syndrome, must have adequate hepatic function as evidenced by a serum bilirubin level <=1.5 x the ULN AND serum levels of aspartate and alanine aminotransferase (AST/ALT) levels <=3 x the ULN for the reference lab (participants with known hepatic metastases must have serum AST/ALT levels <=5 x the ULN for the reference lab).
- Must be recovered from the effects of any prior surgery, radiotherapy or systemic antineoplastic therapy.
Who cannot join
- Has a known hypersensitivity to MK-8776 or gemcitabine or to any of their excipients or has received therapy with another Checkpoint kinase 1 (CHK1) inhibitor.
- Has received any prohibited medication more recently than the indicated washout period prior to first dose of protocol therapy or must continue to receive prohibited medications. Prohibited medications: cytochrome P450 1A2 inhibitors, any chemotherapy, or investigational drugs.
- Has significant underlying cardiac conduction system abnormalities such as bifascicular or greater block (eg, right bundle branch block with left anterior hemiblock or first degree atrioventricular block), fixed-rate pacemaker, or chronic atrial fibrillation with variable ventricular rate.
- Has persistent, unresolved Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 >=Grade 2 drug-related toxicity (except alopecia, erectile impotence, hot flashes, and decreased libido) associated with previous treatment.
- Has known human immunodeficiency virus (HIV), hepatitis B, hepatitis C, or a known history of liver cirrhosis or active alcohol abuse.
- Is New York Heart Association (NYHA) Class III.
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- Has any other medical or psychiatric condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results.
- Has undergone major surgery within 3 weeks prior to first study drug administration after enrollment.
- Has central nervous system (CNS) or leptomeningeal metastases.
- Has received radiation therapy within 3 weeks prior to first study drug administration after enrollment or radiation therapy to >25% of bone marrow.
- Has received >3 prior chemotherapy regimens (may have received prior gemcitabine). A participant may not have experienced any CTCAE v 3.0 >Grade 1 myelotoxicity (neutropenia and/or thrombocytopenia) with any prior regimen, including gemcitabine. Participants with >3 prior chemotherapy regimens, one or more of which were targeted, nonmyelosuppressive agents, may be considered on a case-by-case basis after discussion with the sponsor.
- Has undergone previous allogeneic or autologous stem cell transplant.
- Has had any of the following within 6 months prior to first study drug administration after enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or seizure disorder.
- Has a known bleeding diathesis, eg, hemophilia.
- Has a baseline QTc interval >450 msec (ie, CTCAE v 3.0 Grade ≥2) at screening (within 21 days prior to 1st dose of MK-8776, mean of triplicate readings within approximately 5 minutes).
- History of risk factors for Torsades de Pointes, including clinical history of heart failure, hypo- or hyperkalemia or hypomagnesemia (supplementation or other appropriate interventions to bring levels within normal institutional limits prior to administration of MK-8776 is acceptable), or family history of Long QT Syndrome.
- Currently a smoker and/or is likely to smoke during the study.
- Female participant who is breast-feeding, pregnant, or intends to become pregnant.
- Participating in any other interventional clinical study. (Participants participating in another noninterventional study may be considered after discussion with the sponsor.)
- Part of the staff personnel directly related to this study.
- Family member of one of the investigational staff.
About this study
Official title: A Phase 1 Dose-Escalation Study of SCH 900776 as Monotherapy and in Combination With Gemcitabine in Subjects With Advanced Solid Tumors or Lymphoma
This study of MK-8776 (SCH 900776) will evaluate its safety and tolerability when given as monotherapy or in combination with gemcitabine to participants with advanced solid tumors or lymphoma. Participants will be enrolled in cohorts that will receive sequentially higher doses of MK-8776 in combination with standard doses of gemcitabine The recommended combination doses for a Phase 2 trial (combination-RP2D) will be determined based on safety and biological activity. Up to 10 to 15 additional participants may be studied at the combination-RP2D.
- Conditions
- Hodgkin Disease, Lymphoma, Non-Hodgkin, Neoplasms
- Being tested
- MK-8776, Gemcitabine
- Medical subject headings
- Hodgkin Disease, Lymphoma, Non-Hodgkin, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-8776Drug
Also called SCH 900776
IV infusion
GemcitabineDrug
Also called GEMZAR®
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Participants received MK-8776 10 mg/m^2 given as monotherapy as an intravenous (IV) infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Receives: Drug: MK-8776; Drug: Gemcitabine |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Participants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Receives: Drug: MK-8776; Drug: Gemcitabine |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Participants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Receives: Drug: MK-8776; Drug: Gemcitabine |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Receives: Drug: MK-8776; Drug: Gemcitabine |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Receives: Drug: MK-8776; Drug: Gemcitabine |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | Experimental | Participants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Receives: Drug: MK-8776; Drug: Gemcitabine |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | Experimental | Participants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Receives: Drug: MK-8776; Drug: Gemcitabine |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | Experimental | Participants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Receives: Drug: MK-8776; Drug: Gemcitabine |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | Experimental | Participants received MK-8776 200 mg given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. Receives: Drug: MK-8776; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0)
During Cycle 0, a DLT was defined as: CTCAE v 3.0 Grade 3 neutropenia or thrombocytopenia lasting ≥3 days; any CTCAE v 3.0 Grade 4 neutropenia or thrombocytopenia; neutropenic fever; any CTCAE v. 3.0 ≥ Grade 3 QT interval corrected by Fridericia (QTcF) prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s); delay in Cycle 1 Day 1 beyond 3 weeks due to continuing toxicity. During Cycle 1, a DLT was defined as: CTCAE v 3.0 Grade 4 neutropenia that persists for ≥7 days; neutropenic fever; CTCAE v 3.0 Grade 4 thrombocytopenia; CTCAE v 3.0 ≥ Grade 3 thrombocytopenia with bleeding; any CTCAE v 3.0 QTc ≥ Grade 3 QTcF prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s).
Measured: Through Cycle 0 and Cycle 1 (Up to 42 days)
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who experienced an AE is presented.
Measured: Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment)
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who discontinued study treatment due to an AE is presented.
Measured: Up to approximatey 66 weeks
Secondary outcomes (4)
MK-8776 Maximum Plasma Concentration (Cmax)
The Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.
Measured: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last)
AUC0-last was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion. AUC0-last was calculated by the linear trapezoidal method.
Measured: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
Time of MK-8776 Cmax (Tmax)
The time of Cmax of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.
Measured: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
MK-8776 Terminal Phase Half-Life (t1/2)
The t1/2 of MK-8776 was assessed in Cycle 0 and in Cycle 1. On Day 1 of Cycle 0 and Cycle 1, plasma samples were obtained from all participants before infusion, at end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion.
Measured: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2008 (estimated)
- Study start17 Oct 2008
- Primary completion28 May 2011
- Study completion28 May 2011
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hodgkin DiseaseStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00779584
- Sponsor's protocol ID
- P05248
- Other IDs
- MK-8776-002
- Status last verified
- Jul 2018
- First submitted
- 22 Oct 2008
- Last updated
- 27 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Daud AI, Ashworth MT, Strosberg J, Goldman JW, Mendelson D, Springett G, Venook AP, Loechner S, Rosen LS, Shanahan F, Parry D, Shumway S, Grabowsky JA, Freshwater T, Sorge C, Kang SP, Isaacs R, Munster PN. Phase I dose-escalation trial of checkpoint kinase 1 inhibitor MK-8776 as monotherapy and in combination with gemcitabine in patients with advanced solid tumors. J Clin Oncol. 2015 Mar 20;33(9):1060-6. doi: 10.1200/JCO.2014.57.5027. Epub 2015 Jan 20.
PubMed 25605849
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose-Escalation Study of SCH 900776 as Monotherapy and in Combination With Gemcitabine in Subjects With Advanced Solid Tumors or Lymphoma
- ClinicalTrials.gov ID
- NCT00779584
- Acronym / sponsor ID
- P05248
- Conditions
- Hodgkin Disease, Lymphoma, Non-Hodgkin, Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 17 Oct 2008 (actual)
- Primary completion
- 28 May 2011 (actual)
- Study completion
- 28 May 2011 (actual)
- First posted
- 24 Oct 2008 (estimated)
- Results
- Posted 20 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study of MK-8776 (SCH 900776) will evaluate its safety and tolerability when given as monotherapy or in combination with gemcitabine to participants with advanced solid tumors or lymphoma. Participants will be enrolled in cohorts that will receive sequentially higher doses of MK-8776 in combination with standard doses of gemcitabine The recommended combination doses for a Phase 2 trial (combination-RP2D) will be determined based on safety and biological activity. Up to 10 to 15 additional participants may be studied at the combination-RP2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| MK-8776 10mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Drug: MK-8776, Drug: GemcitabineParticipants received MK-8776 10 mg/m^2 given as monotherapy as an intravenous (IV) infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. |
| MK-8776 20mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Drug: MK-8776, Drug: GemcitabineParticipants received MK-8776 20 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. |
| MK-8776 40mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Drug: MK-8776, Drug: GemcitabineParticipants received MK-8776 40 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. |
| MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Drug: MK-8776, Drug: GemcitabineParticipants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. |
| MK-8776 112mg/m^2+Gemcitabine 800mg/m^2 | Experimental | Drug: MK-8776, Drug: GemcitabineParticipants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 800 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. |
| MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2 | Experimental | Drug: MK-8776, Drug: GemcitabineParticipants received MK-8776 80 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. |
| MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2 | Experimental | Drug: MK-8776, Drug: GemcitabineParticipants received MK-8776 112 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. |
| MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2 | Experimental | Drug: MK-8776, Drug: GemcitabineParticipants received MK-8776 150 mg/m^2 given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. |
| MK-8776 200mg+Gemcitabine 1000mg/m^2 | Experimental | Drug: MK-8776, Drug: GemcitabineParticipants received MK-8776 200 mg given as monotherapy as an IV infusion on Cycle 0 Day 1 and as combination therapy with gemcitabine 1000 mg/m^2 starting with Cycle 1 on Days 1 and 8 of a 21-day treatment cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Must have a diagnosis of an advanced solid tumor malignancy or lymphoma (non-Hodgkin's or Hodgkin's lymphoma).
- Must have histological or cytological evidence of malignancy.
- Must have an advanced malignancy, metastatic or unresectable. For Part A of the study, the metastatic or unresectable malignancy should have recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists, or for which they are not candidates for standard therapy. For Parts B and C of the study, participants with advanced tumors for which gemcitabine is considered standard therapy (eg, pancreatic cancer), may be enrolled without having received prior gemcitabine. Standard therapy is defined as therapy that is approved in a particular line of therapy or considered as standard of care based on published peer reviewed data in a specific line of therapy.
- Gemcitabine-naïve participants with tumors known to be responsive to gemcitabine or participants previously treated with gemcitabine who did not progress while on treatment or who are currently still responding to treatment should only be enrolled in cohorts for which gemcitabine doses are >=1000 mg/m². Participants previously treated with gemcitabine, whose disease has progressed wile on treatment, can be enrolled to any part.
- Must be ambulatory with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (21 listed)
- Has a known hypersensitivity to MK-8776 or gemcitabine or to any of their excipients or has received therapy with another Checkpoint kinase 1 (CHK1) inhibitor.
- Has received any prohibited medication more recently than the indicated washout period prior to first dose of protocol therapy or must continue to receive prohibited medications. Prohibited medications: cytochrome P450 1A2 inhibitors, any chemotherapy, or investigational drugs.
- Has significant underlying cardiac conduction system abnormalities such as bifascicular or greater block (eg, right bundle branch block with left anterior hemiblock or first degree atrioventricular block), fixed-rate pacemaker, or chronic atrial fibrillation with variable ventricular rate.
- Has persistent, unresolved Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 >=Grade 2 drug-related toxicity (except alopecia, erectile impotence, hot flashes, and decreased libido) associated with previous treatment.
- Has known human immunodeficiency virus (HIV), hepatitis B, hepatitis C, or a known history of liver cirrhosis or active alcohol abuse.
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 |
|---|---|---|
| MK-8776Also: SCH 900776IV infusion | Drug | MK-8776 10mg/m^2+Gemcitabine 800mg/m^2, MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2, MK-8776 112mg/m^2+Gemcitabine 800mg/m^2, MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2, MK-8776 200mg+Gemcitabine 1000mg/m^2, MK-8776 20mg/m^2+Gemcitabine 800mg/m^2, MK-8776 40mg/m^2+Gemcitabine 800mg/m^2, MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2, MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 |
| GemcitabineAlso: GEMZAR®IV infusion | Drug | MK-8776 10mg/m^2+Gemcitabine 800mg/m^2, MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2, MK-8776 112mg/m^2+Gemcitabine 800mg/m^2, MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2, MK-8776 200mg+Gemcitabine 1000mg/m^2, MK-8776 20mg/m^2+Gemcitabine 800mg/m^2, MK-8776 40mg/m^2+Gemcitabine 800mg/m^2, MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2, MK-8776 80mg/m^2+Gemcitabine 800mg/m^2 |
Primary outcome
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0)
Time frame: Through Cycle 0 and Cycle 1 (Up to 42 days)
During Cycle 0, a DLT was defined as: CTCAE v 3.0 Grade 3 neutropenia or thrombocytopenia lasting ≥3 days; any CTCAE v 3.0 Grade 4 neutropenia or thrombocytopenia; neutropenic fever; any CTCAE v. 3.0 ≥ Grade 3 QT interval corrected by Fridericia (QTcF) prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s); delay in Cycle 1 Day 1 beyond 3 weeks due to continuing toxicity. During Cycle 1, a DLT was defined as: CTCAE v 3.0 Grade 4 neutropenia that persists for ≥7 days; neutropenic fever; CTCAE v 3.0 Grade 4 thrombocytopenia; CTCAE v 3.0 ≥ Grade 3 thrombocytopenia with bleeding; any CTCAE v 3.0 QTc ≥ Grade 3 QTcF prolongation of any duration; any other CTCAE v 3.0 Grade 3 or higher nonhematologic toxicity; or Grade 3 elevation of transaminases that resolved prior to administration of next dose(s) of study drug(s).
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment)
An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who experienced an AE is presented.
Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to approximatey 66 weeks
An AE was defined as any untoward medical occurrence in a participant administered study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could have been any unfavorable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to study treatment. The number of participants who discontinued study treatment due to an AE is presented.
4 secondary outcomes
MK-8776 Maximum Plasma Concentration (Cmax)
Time frame: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
MK-8776 Area Under the Curve of the Plasma Concentration Versus Time From Time Zero to the Time of the Last Analytically Quantifiable Concentration (AUC0-last)
Time frame: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
Time of MK-8776 Cmax (Tmax)
Time frame: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
MK-8776 Terminal Phase Half-Life (t1/2)
Time frame: At end of infusion of MK-8776 (Cycle 0) or gemcitabine (Cycle 1), and at 0.25, 1, 3, 6, 8, 24 and 48 hours after completion of MK-8776 infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25605849Daud AI, Ashworth MT, Strosberg J, Goldman JW, Mendelson D, Springett G, Venook AP, Loechner S, Rosen LS, Shanahan F, Parry D, Shumway S, Grabowsky JA, Freshwater T, Sorge C, Kang SP, Isaacs R, Munster PN. Phase I dose-escalation trial of checkpoint kinase 1 inhibitor MK-8776 as monotherapy and in combination with gemcitabine in patients with advanced solid tumors. J Clin Oncol. 2015 Mar 20;33(9):1060-6. doi: 10.1200/JCO.2014.57.5027. Epub 2015 Jan 20.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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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.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-8776 and Gemcitabine in people with Hodgkin Disease and Lymphoma, Non-Hodgkin, run by Merck Sharp & Dohme LLC.
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 12 inclusion and 21 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 27 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
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 20 Jun 2017). 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?
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 0 and Cycle 1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v 3.0) (time frame: Through Cycle 0 and Cycle 1 (Up to 42 days)). 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?
On the ClinicalTrials.gov record for NCT00779584, which also lists 1 linked publication.
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 Aug 2018.