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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01359696
• Other study ID #: DPM4957g
• Secondary ID: GO00767
• Status: Completed
• Phase: Phase 1
• First received: May 23, 2011
• Last updated: April 11, 2017
• Start date: July 11, 2011
• Est. completion date: May 29, 2014

Study information

• Verified date: April 2017
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter, Phase I, dose-escalation study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GDC-0425 administered with and without gemcitabine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 29, 2014
• Est. primary completion date: May 29, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• GDC-0425
Oral escalating dose
• gemcitabine
Intravenous repeating dose

Locations

Country	Name	City	State
France	Institut Gustave Roussy; Ser. de Med. Nucleaire; Cancerologie Endo	Villejuif
United States	Karmanos Cancer Institute..	Detroit	Michigan
United States	Sarah Cannon Cancer Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of all adverse events graded according to NCI CTCAE, v4.0		Up to 1 year
Primary	Incidence of dose limiting toxicities (DLTs)		Up to 35 days
Primary	Pharmacokinetic property of GDC-0425: determination of plasma drug concentration		Up to 12 months or early study discontinuation
Primary	Pharmacokinetic property of GDC-0425: exposure		Up to 12 months or early study discontinuation
Primary	Pharmacokinetic property of GDC-0425: half-life		Up to 12 months or early study discontinuation
Primary	Severity of all adverse events graded according to NCI CTCAE, v4.0		Up to 1 year
Secondary	Antitumor activity of GDC-0425 in combination with gemcitabine: determination of tumor response using RECIST v1.1 for patients with measurable disease		Up to 12 months or early study discontinuation