Clinical trial NCT01359696: A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0425 Administered With and Without Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: solid cancers
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-05-25
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Incidence of all adverse events graded according to NCI CTCAE, v4.0
timeFrame: Up to 1 year
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: Up to 35 days
measure: Pharmacokinetic property of GDC-0425: determination of plasma drug concentration
timeFrame: Up to 12 months or early study discontinuation
measure: Pharmacokinetic property of GDC-0425: exposure
timeFrame: Up to 12 months or early study discontinuation
measure: Pharmacokinetic property of GDC-0425: half-life
timeFrame: Up to 12 months or early study discontinuation
measure: Severity of all adverse events graded according to NCI CTCAE, v4.0
timeFrame: Up to 1 year
Secondary outcomes:
measure: Antitumor activity of GDC-0425 in combination with gemcitabine: determination of tumor response using RECIST v1.1 for patients with measurable disease
timeFrame: Up to 12 months or early study discontinuation
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Institute..
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Villejuif
country: France
facility: Institut Gustave Roussy; Ser. de Med. Nucleaire; Cancerologie Endo
Study officials:
affiliation: Genentech, Inc.
name: Chia Portera, M.D., Ph.D.
role: STUDY_DIRECTOR
References: