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

• Status: Completed
• Trial end date: 2018-01-11
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genentech, Inc.
• Treatments: GDC-0575; Gemcitabine

Criteria

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