A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0425 Administered With and Without Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01359696
First received: May 23, 2011
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

This is an open-label, multicenter, Phase I, dose-escalation study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GDC-0 425 administered with and without gemcitabine.


Condition Intervention Phase
Solid Tumour
Drug: GDC-0425
Drug: gemcitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Phase I, Dose Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0425 Administered With and Without Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Incidence of all adverse events graded according to NCI CTCAE, v4.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Incidence of dose limiting toxicities (DLTs) [ Time Frame: Up to 35 days ] [ Designated as safety issue: No ]
  • Pharmacokinetic property of GDC-0425: determination of plasma drug concentration [ Time Frame: Up to 12 months or early study discontinuation ] [ Designated as safety issue: No ]
  • Pharmacokinetic property of GDC-0425: exposure [ Time Frame: Up to 12 months or early study discontinuation ] [ Designated as safety issue: No ]
  • Pharmacokinetic property of GDC-0425: half-life [ Time Frame: Up to 12 months or early study discontinuation ] [ Designated as safety issue: No ]
  • Severity of all adverse events graded according to NCI CTCAE, v4.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antitumor activity of GDC-0425 in combination with gemcitabine: determination of tumor response using RECIST v1.1 for patients with measurable disease [ Time Frame: Up to 12 months or early study discontinuation ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: July 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: GDC-0425
Oral escalating dose
Drug: gemcitabine
Intravenous repeating dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
  • Signed Informed Consent Form
  • Histologically or cytologically documented, locally advanced or metastatic solid tumors or lymphoma for which standard therapy either does not exist or has proven ineffective or intolerable
  • Adequate hematologic and end-organ (liver and kidney) function
  • For female patients of childbearing potential and male patients with partners of childbearing potential, agreement by the patient that the patient and/or partner will use an effective form of contraception
  • Patients enrolled in certain phases must be willing to provide fresh and/or archival tumor samples

Exclusion Criteria:

  • History of prior significant toxicity from a same class of agents as GDC-0425 or gemcitabine requiring discontinuation of treatment
  • Allergy, hypersensitivity or contraindication to the GDC-0425 formulation or gemcitabine
  • Experimental therapy or anti-cancer therapy within 4 weeks prior to the first dose of study drug treatment
  • Radiotherapy within 2 weeks prior to first dose of study drug treatment
  • More than two regimens of cytotoxic chemotherapy for the treatment of locally advanced or metastatic cancer
  • History of receiving high-dose chemotherapy requiring bone marrow or stem cell support
  • History of receiving radiation to more than 25% of bone marrow-bearing areas
  • Acute drug-related toxicities from previous therapies have not resolved prior to study entry, except for alopecia and mild neuropathy
  • Current severe, uncontrolled systemic disease (including but not limited to clinically significant cardiovascular, pulmonary, or renal disease or ongoing or active infection) excluding cancer
  • Significant heart disease and heart dysfunction including but not limited to uncontrolled severe hypertension, heart failure, and reduced cardiac contractility
  • Uncontrolled ascites, due to diseases other than cancer
  • Inability or unwillingness to swallow pills/capsules
  • History of malabsorption or other condition that would interfere with drug absorption
  • Any history of active stomach and/or intestine bleeding within the 6 months prior to screening
  • Known HIV infection
  • Pregnancy, lactation, or breastfeeding
  • Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
  • Inability to comply with study and follow up procedures
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01359696

Locations
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Tennessee
Nashville, Tennessee, United States, 37203
France
Villejuif, France, 94805
Sponsors and Collaborators
Genentech
Investigators
Study Director: Chia Portera, M.D., Ph.D. Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01359696     History of Changes
Other Study ID Numbers: DPM4957g, GO00767
Study First Received: May 23, 2011
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech:
solid cancers

Additional relevant MeSH terms:
Neoplasms
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