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CompletedNCT00779584Updated Aug 27, 2018Results posted

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 interventional study of MK-8776 and Gemcitabine in Hodgkin Disease, Lymphoma, Non-Hodgkin and Neoplasms, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-08-27.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
45
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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. 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.

02

Conditions studied

  • Hodgkin Disease
  • Lymphoma, Non-Hodgkin
  • Neoplasms
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 45 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.
  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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.
  • 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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
45 participants (actual)

Study arms

  • Experimental
    MK-8776 10mg/m^2+Gemcitabine 800mg/m^2

    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.

    Drug: MK-8776 · Drug: Gemcitabine

  • Experimental
    MK-8776 20mg/m^2+Gemcitabine 800mg/m^2

    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.

    Drug: MK-8776 · Drug: Gemcitabine

  • Experimental
    MK-8776 40mg/m^2+Gemcitabine 800mg/m^2

    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.

    Drug: MK-8776 · Drug: Gemcitabine

  • Experimental
    MK-8776 80mg/m^2+Gemcitabine 800mg/m^2

    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.

    Drug: MK-8776 · Drug: Gemcitabine

  • Experimental
    MK-8776 112mg/m^2+Gemcitabine 800mg/m^2

    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.

    Drug: MK-8776 · Drug: Gemcitabine

  • Experimental
    MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2

    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.

    Drug: MK-8776 · Drug: Gemcitabine

  • Experimental
    MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2

    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.

    Drug: MK-8776 · Drug: Gemcitabine

  • Experimental
    MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2

    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.

    Drug: MK-8776 · Drug: Gemcitabine

  • Experimental
    MK-8776 200mg+Gemcitabine 1000mg/m^2

    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.

    Drug: MK-8776 · Drug: Gemcitabine

Interventions

  • DrugMK-8776

    IV infusion

    Also known as: SCH 900776

  • DrugGemcitabine

    IV infusion

    Also known as: GEMZAR®

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: Through Cycle 0 and Cycle 1 (Up to 42 days)

  2. 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.

    Time frame: Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment)

  3. 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.

    Time frame: Up to approximatey 66 weeks

Secondary outcomes

  1. 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.

    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

  2. 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.

    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

  3. 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.

    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

  4. 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.

    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

07

Results

Posted Jun 20, 2017

Participant flow

Participant flow — Overall Study
MilestoneMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2
Started337676832
Treated337674832
Completed000000000
Not completed337676832
Withdrew: Protocol violation000001000
Withdrew: Withdrawal by subject112002100
Withdrew: Lost to follow-up000010000
Withdrew: Progression of disease012651421
Withdrew: Adverse event102000211
Withdrew: Symptomatic deterioration111001100
Withdrew: Ongoing in study000011000

Outcome measures

PrimaryNumber 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).

Time frame:
Through Cycle 0 and Cycle 1 (Up to 42 days)
Reported as:
Number · Participants
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)
ParticipantsMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2
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)001020100
PrimaryNumber 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.

Time frame:
Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment)
Reported as:
Number · Participants
Number of Participants Who Experienced an Adverse Event (AE)
ParticipantsMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2
Number of Participants Who Experienced an Adverse Event (AE)337674832
PrimaryNumber 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.

Time frame:
Up to approximatey 66 weeks
Reported as:
Number · Participants
Number of Participants Who Discontinued Study Treatment Due to an AE
ParticipantsMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2
Number of Participants Who Discontinued Study Treatment Due to an AE102000211
SecondaryMK-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.

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
Reported as:
Mean · ng/mL
MK-8776 Maximum Plasma Concentration (Cmax)
ng/mLMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2
Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2)414 ± 2571010 ± 1971220 ± 3664970 ± 15005270 ± 37302960 ± 12906210 ± 21606220 ± 25504860 ± NA
Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2)445 ± 2491650 ± 1520962 ± 4543700 ± 19304710 ± 23103610 ± 22904690 ± 26104940 ± NA3700 ± NA
SecondaryMK-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.

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
Reported as:
Mean · ng*hr/mL
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)
ng*hr/mLMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2
Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2)565 ± 1711400 ± 4482250 ± 9485060 ± 19209050 ± 55004040 ± 10109240 ± 574018500 ± 80008440 ± NA
Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2)539 ± 3071570 ± 4231900 ± 8594540 ± 166010300 ± 63704660 ± 8156900 ± 312013000 ± NA16900 ± NA
SecondaryTime 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.

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
Reported as:
Mean · hr
Time of MK-8776 Cmax (Tmax)
hrMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2
Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2)0.27 ± 0.030.26 ± 0.010.29 ± 0.060.24 ± 0.030.30 ± 0.080.26 ± 0.050.23 ± 0.020.48 ± 0.020.49 ± NA
Cycle 1 (n=3, 3, 7, 5, 6, 4, 6, 1, 2)0.26 ± 0.010.27 ± 0.020.35 ± 0.130.25 ± 0.060.28 ± 0.060.26 ± 0.030.23 ± 0.010.50 ± NA0.57 ± NA
SecondaryMK-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.

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
Reported as:
Mean · hr
MK-8776 Terminal Phase Half-Life (t1/2)
hrMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2
Cycle 0 (n=3, 3, 7, 6, 7, 4, 8, 3, 2)6.29 ± 1.979.33 ± 5.098.45 ± 2.957.44 ± 0.4355.94 ± 1.628.13 ± 1.307.14 ± 1.909.46 ± 2.116.30 ± NA
Cycle 1 (n=3, 3, 6, 6, 7, 4, 7, 1, 2)6.24 ± 2.038.57 ± 4.548.23 ± 1.719.01 ± 2.517.29 ± 1.267.87 ± 2.117.98 ± 1.217.59 ± NA9.89 ± NA

Adverse events

Collected over Up to approximately 72 weeks (Up to approximately 6 weeks after last dose of study treatment). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
MK-8776 10mg/m^2+Gemcitabine 800mg/m^2—2/3 (66.7%)3/3 (100%)
MK-8776 20mg/m^2+Gemcitabine 800mg/m^2—1/3 (33.3%)3/3 (100%)
MK-8776 40mg/m^2+Gemcitabine 800mg/m^2—3/7 (42.9%)7/7 (100%)
MK-8776 80mg/m^2+Gemcitabine 800mg/m^2—1/6 (16.7%)6/6 (100%)
MK-8776 112mg/m^2+Gemcitabine 800mg/m^2—2/7 (28.6%)7/7 (100%)
MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2—3/4 (75%)4/4 (100%)
MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2—4/8 (50%)8/8 (100%)
MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2—0/3 (0%)3/3 (100%)
MK-8776 200mg Flat Dose+Gemcitabine 1000mg/m^2—2/2 (100%)2/2 (100%)
Most frequent serious events
Showing 10 of 25
Most frequent serious events
EventMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg Flat Dose+Gemcitabine 1000mg/m^2
ABDOMINAL PAINGastrointestinal disorders1/31/31/70/60/70/41/80/31/2
CHOLANGITISHepatobiliary disorders0/30/30/70/60/70/40/80/31/2
HIP FRACTUREInjury, poisoning and procedural complications0/30/30/70/60/70/40/80/31/2
CONSTIPATIONGastrointestinal disorders1/30/30/70/60/70/40/80/30/2
PNEUMOCYSTIS JIROVECI PNEUMONIAInfections and infestations1/30/30/70/60/70/40/80/30/2
DYSPNOEARespiratory, thoracic and mediastinal disorders1/30/30/70/60/70/40/80/30/2
DUODENAL OBSTRUCTIONGastrointestinal disorders0/30/30/70/60/71/40/80/30/2
VOMITINGGastrointestinal disorders0/30/30/70/60/71/40/80/30/2
PYREXIAGeneral disorders0/30/30/71/60/71/40/80/30/2
HYPERBILIRUBINAEMIAHepatobiliary disorders0/30/30/70/60/71/41/80/30/2
Most frequent other events
Showing 10 of 169
Most frequent other events
EventMK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg Flat Dose+Gemcitabine 1000mg/m^2
NAUSEAGastrointestinal disorders3/31/32/73/64/73/42/83/31/2
FATIGUEGeneral disorders2/32/35/75/66/74/44/81/30/2
ELECTROCARDIOGRAM QT PROLONGEDInvestigations0/30/32/70/61/71/42/83/31/2
DECREASED APPETITEMetabolism and nutrition disorders1/32/33/73/62/74/41/80/30/2
ABDOMINAL PAINGastrointestinal disorders2/30/31/72/61/72/42/80/30/2
VOMITINGGastrointestinal disorders2/30/32/71/64/71/40/81/30/2
NON-CARDIAC CHEST PAINGeneral disorders0/32/30/70/60/70/40/80/30/2
DYSPNOEA EXERTIONALRespiratory, thoracic and mediastinal disorders1/32/30/71/62/70/41/80/30/2
OEDEMA PERIPHERALGeneral disorders1/30/34/73/60/70/40/80/31/2
NEUTROPENIABlood and lymphatic system disorders0/30/32/71/61/72/44/80/30/2

Baseline characteristics

Age, Continuous
Age, Continuous(Years)MK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2Total
Mean54.3 ± 16.054.3 ± 8.664.0 ± 16.155.5 ± 5.051.1 ± 5.759.0 ± 13.459.9 ± 9.169.3 ± 5.569.0 ± 8.558.8 ± 11.2
Sex: Female, Male
Sex: Female, Male(Participants)MK-8776 10mg/m^2+Gemcitabine 800mg/m^2MK-8776 20mg/m^2+Gemcitabine 800mg/m^2MK-8776 40mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 800mg/m^2MK-8776 112mg/m^2+Gemcitabine 800mg/m^2MK-8776 80mg/m^2+Gemcitabine 1000mg/m^2MK-8776 112mg/m^2+Gemcitabine 1000mg/m^2MK-8776 150mg/m^2+Gemcitabine 1000mg/m^2MK-8776 200mg+Gemcitabine 1000mg/m^2Total
Female20224231218
Male13543452027
08

Study locations

No study locations are listed for this record.

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References and documents

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 ↗

Individual participant data

Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 27, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00779584
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Oct 24, 2008
Start date
Oct 17, 2008
Primary completion
May 28, 2011
Completion
May 28, 2011
Results posted
Jun 20, 2017
Last update
Aug 27, 2018

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2018. You cannot join it, but the record below documents what was studied.

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