Mode
Text Size
Log in / Sign up
Phase 1 Completed N=45 Treatment

A Dose-escalation Study of MK-8776 (SCH 900776) With and Without Gemcitabine in Participants With Solid Tumors or Lymphoma (MK-8776-002/P05248)

Hodgkin Disease · Lymphoma, Non-Hodgkin · Neoplasms
Source: ClinicalTrials.gov NCT00779584 ↗
Enrolled (actual)
45
Serious AEs
41.9%
Results posted
Jun 2017
Primary outcomePrimary: 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) — 0; 0; 1; 0 Participants

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
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)
0; 0; 1; 0; 2; 0
PRIMARY
Number of Participants Who Experienced an Adverse Event (AE)
3; 3; 7; 6; 7; 4
PRIMARY
Number of Participants Who Discontinued Study Treatment Due to an AE
1; 0; 2; 0; 0; 0
SECONDARY
MK-8776 Maximum Plasma Concentration (Cmax)
414; 1010; 1220; 4970; 5270; 2960
SECONDARY
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)
565; 1400; 2250; 5060; 9050; 4040
SECONDARY
Time of MK-8776 Cmax (Tmax)
0.27; 0.26; 0.29; 0.24; 0.30; 0.26
SECONDARY
MK-8776 Terminal Phase Half-Life (t1/2)
6.29; 9.33; 8.45; 7.44; 5.94; 8.13

Eligibility Criteria

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 60 mL/min.
  • Participants, except those with known Gilbert's Syndrome, must have adequate hepatic function as evidenced by a serum bilirubin level =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, nonmyelosupp
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00779584). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

Back to search