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An Open-Label, Phase I, Dose-Escalation Study of PI3-Kinase Inhibitor (GDC-0941) in Patients With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma for Which Standard Therapy Either Does Not Exist or Has Proven Ineffective or Intolerable


Phase 1
18 Years
N/A
Not Enrolling
Both
Non-Hodgkin's Lymphoma, Solid Cancers

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Trial Information

An Open-Label, Phase I, Dose-Escalation Study of PI3-Kinase Inhibitor (GDC-0941) in Patients With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma for Which Standard Therapy Either Does Not Exist or Has Proven Ineffective or Intolerable


Inclusion Criteria:



- Histologically or cytologically documented, incurable, locally advanced or metastatic
solid malignancy or NHL without leukemic phase that has progressed or has failed to
respond to at least one prior regimen

- Multiple myeloma (MM) patients (only in Stage 2): documented pathologic diagnosis of
MM that has relapsed or that has failed to respond after treatment with at least one
prior systemic therapy (other than corticosteroid monotherapy)

- Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors
(RECIST) or per International Working Group (IWG) response criteria for Non-Hodgkin's
lymphoma (NHL) patients

- Life expectancy of >= 12 weeks

- Documented willingness to use an effective means of contraception for both men and
women while participating in the study

- For patients participating in Stage 1 after an adequate exposure has been predicted
or observed on the basis of PK analysis and for approximately 12 patients
participating in Stage 2 (excluding patients with MM): A biopsy-accessible lesion
from which tissue can be obtained safely with CT guidance or direct visualization and
agreement from the patient to undergo sequential (pre-treatment and post-treatment)
biopsies.

- For patients participating in Stage 2 DCE-MRI and MRS imaging: Patients will have at
least one metastatic liver lesion measuring >= 5 cm in one dimension or one tumor
lesion elsewhere measuring >= 2 cm in one dimension (lung and mediastinum lesions do
not qualify) on the basis of CT scans

Exclusion Criteria:

- Leptomeningeal disease as the only manifestation of the current malignancy

- History of Type 1 or 2 diabetes mellitus requiring regular medication

- Any condition requiring anti-coagulants, such as warfarin, heparin, or thrombolytics

- Inability or unwillingness to swallow pills

- Malabsorption syndrome or other condition that would interfere with enteral
absorption

- Known untreated CNS malignancies or treated brain metastases that are not
radiographically stable for >= 3 months

- Congenital long QT syndrome or QTc > 500 msec, as determined by at least two of the
three baseline ECG measurements

- Active congestive heart failure or ventricular arrhythmia requiring medication

- Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive
weeks prior to enrollment

- Active infection requiring intravenous (IV) antibiotics

- Patients requiring any daily supplemental oxygen

- DLco, 50% predicted value corrected for AV and Hgb prior to initiation of study
treatment

- Uncontrolled hypomagnesemia or hypokalemia, defined as values below the lower limit
of normal (LLN) or hypercalcemia above the ULN for the institution despite adequate
electrolyte supplementation or management

- Clinically significant history of liver disease, including viral or other hepatitis,
current alcohol abuse, or cirrhosis

- Known human immunodeficiency virus (HIV) infection

- Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic
dysfunction, physical examination finding, or clinical laboratory finding giving
reasonable suspicion of a disease or condition that contraindicates the use of an
investigational drug or that may affect the interpretation of the results or renders
the patients at high risk from treatment complications

- Significant traumatic injury within 3 weeks before Day 1

- Major surgical procedure within 4 weeks prior to initiation of study treatment

- Prior allogeneic hematopoietic stem cell transplantation (HSCT) at any time or
autologous HSCT within 12 weeks of study entry

- Treatment with chemotherapy, hormonal therapy (except GnRH agonists or antagonists
for prostate cancer), immunotherapy, biologic therapy, or radiation therapy (except
palliative radiation to bony metastases) as cancer therapy within 4 weeks prior to
initiation of study treatment (exceptions are kinase inhibitors that are approved by
the local regulatory authorities, which may be used within 2 weeks prior to
initiation of study treatment, provided that any drug-related toxicity has completely
resolved and after approval by the Medical Monitor has been granted)

- Palliative radiation to bony metastases within 2 weeks prior to initiation of study
treatment

- Need for chronic corticosteroid therapy

- Treatment with an investigational agent within 4 weeks prior to initiation of study
treatment

- Unresolved toxicity from prior therapy, except for alopecia and Grade 1 peripheral
neuropathy

- Pregnancy or lactation

- Inability to comply with study and follow-up procedures

- For patients eligible to participate in Stage 2 DCE-MRI and MRS assessments, any
contraindication to MRI examination, including the following:

Imbedded metallic material/devices (metal implants or large tattoos in the field of view)

Severe claustrophobia

Physical characteristics (weight or size) that exceed the capabilities of the MRI scanner

Known allergy or hypersensitivity reactions to gadolinium, verse

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Occurrence of adverse events by NCI CTCAE grade and associated dose of GDC-0941

Outcome Time Frame:

Through study completion or early study discontinuation

Safety Issue:

No

Principal Investigator

Gallia Levy, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

Genentech

Authority:

United States: Food and Drug Administration

Study ID:

GDC4254g

NCT ID:

NCT00876122

Start Date:

March 2008

Completion Date:

January 2013

Related Keywords:

  • Non-Hodgkin's Lymphoma, Solid Cancers
  • NHL
  • Metastatic Solid Tumors
  • PI3K Inhibitors
  • PI3K
  • Lymphoma
  • Lymphoma, Non-Hodgkin

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