A Phase 1 Dose-escalation Study of a Cell Cycle Inhibitor With and Without Gemcitabine in Patients With Solid Tumors or Lymphoma (Study P05248)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00779584
First received: October 22, 2008
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

This first study in humans of 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 SCH 900776 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.


Condition Intervention Phase
Hodgkin Disease
Lymphoma, Non-Hodgkin
Neoplasms
Drug: SCH 900776
Drug: Gemcitabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Dose-limiting toxicities and biologic activity used to determine the recommended Phase 2 combination doses of SCH 900776 and gemcitabine [ Time Frame: All study visits ] [ Designated as safety issue: Yes ]

Enrollment: 45
Study Start Date: October 2008
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SCH 900776 as monotherapy and in combination with gemcitabine Drug: SCH 900776
SCH 900776 will be administered to sequential escalating dose cohorts as an intravenous infusion over at least 30 minutes. Doses of SCH 900776 will either be doubled or increased by 40%, depending on the toxicities observed and the specific dose level, and by 20% increments above 200 mg. SCH 900776 will be given as monotherapy on Cycle 0 Day 1 for participants in the dose escalation portion, and starting with Cycle 1 in combination with gemcitabine on Days 1 and 8 of a 21 day treatment cycle for all participants
Drug: Gemcitabine
Depending on the part of the dose escalation portion of the trial, the participant will receive 800 mg/m2, 1000 mg/m2 or based upon safety, 1250 mg/m2. Starting with Cycle 1, gemcitabine will be administered intravenously over at least 30 minutes on Days 1 and 8 of a 21-day treatment cycle.
Other Name: Gemzar

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • Must be 18 years or older, of either sex, and of any race.
  • 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:

  • Has a known hypersensitivity to SCH 900776 or gemcitabine or to any of their excipients or has received therapy with another 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 more than three 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 more than three 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 SCH 900776, 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 SCH 900776 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. (Subject 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00779584     History of Changes
Other Study ID Numbers: P05248
Study First Received: October 22, 2008
Last Updated: September 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 18, 2014