A Study of GDC-0575 Alone and in Combination With Gemcitabine in Participants With Refractory Solid Tumors or Lymphoma

Status:	Completed
Conditions:	Lymphoma
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	3/2/2019
Start Date:	March 23, 2012
End Date:	January 11, 2018

An Open-label, Phase I, Dose Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0575 Administered Alone and in Combination With Gemcitabine in Patients With Refractory Solid Tumors or Lymphoma

This open-label, multicenter, Phase I, dose-escalation study will evaluate the safety,
tolerability, and pharmacokinetics (PK) of GDC-0575 administered alone or in combination with
gemcitabine in participants with refractory solid tumors or lymphoma. In Stage 1, cohorts of
participants will receive multiple ascending oral doses of GDC-0575 alone or in combination
with intravenous gemcitabine. In Stage 2, participants will receive GDC-0575 orally in
combination with intravenous gemcitabine at or below the maximum tolerated dose determined in
Stage 1. Anticipated time on study treatment is until disease progression or unacceptable
toxicity occurs, up to approximately 5 years.

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- 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

- Life expectancy greater than or equal to (>=) 12 weeks, in the opinion of the
investigator

- Adequate hematologic, liver, and renal function

- For Stage 2: Participants with human epidermal growth factor receptor 2 (HER2)
negative, estrogen-receptor (ER) negative, and progesterone-receptor (PR) negative
breast cancer

- For Stage 2: Participants with non-mucinous, platinum-resistant ovarian cancer with
documented radiographic progression or relapse according to RECIST within 6 months of
receiving platinum-based chemotherapy

- For Stage 2: Participants with histologically or cytologically confirmed diagnosis of
squamous non-small cell lung cancer (NSCLC); mixed histology that is predominantly
squamous is acceptable

Exclusion Criteria:

- History of prior significant toxicity from a same class of agents as GDC-0575 or
gemcitabine requiring discontinuation of treatment

- All acute toxicities related to prior therapy must have 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 the cancer under study

- History of significant cardiac dysfunction

- History of malabsorption or other condition that would interfere with enteral
absorption

- Known human immunodeficiency virus (HIV) infection

- Pregnancy, lactation or breastfeeding

- Known brain metastases that are untreated, symptomatic, or require therapy to control
symptoms

- Current use of alpha-adrenergic receptor blockers

For Combination Arm only:

- Any contraindication to gemcitabine therapy

- 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

- Irradiation to more than 25% of bone marrow-bearing areas

We found this trial at

sites

Institut Bergonie; Oncologie

229 Cours de l'Argonne
Bordeaux, 33076

from

Bordeaux,