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

Genentech

Status and phase: Completed; Phase 1

Conditions: Lymphoma, Solid Tumor

Treatments: Drug: Gemcitabine; Drug: GDC-0575

Study type: Interventional

Funder types: Industry

Identifiers

NCT01564251

GP28153

2011-005602-30 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 104 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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104 participants in 4 patient groups

Stage 1 Arm 1: GDC-0575 Monotherapy

Experimental group

Description:

Participants will receive escalating doses of GDC-0575, administered orally, for 3 consecutive days, starting on Days 1, 8, and 15 of each 21-day cycle.

Treatment:

Drug: GDC-0575

Stage 1 Arm 2a: GDC-0575 + Gemcitabine (750 or 1000 mg/m^2)

Experimental group

Description:

Participants will receive gemcitabine 750 milligrams per meter square (mg/m\^2) or 1000 mg/m\^2, intravenously, on Days 1 and 8 followed by escalating doses of GDC-0575 orally, on Days 2 and 9 of each 21-day cycle.

Treatment:

Drug: GDC-0575

Drug: Gemcitabine

Stage 1 Arm 2b: GDC-0575 plus Gemcitabine (500 mg/m^2)

Experimental group

Description:

Participants will receive gemcitabine 500 mg/m\^2, intravenously, once weekly for approximately 2 consecutive weeks of any 3-week period and escalating doses of GDC-0575 orally approximately 24-hours after each gemcitabine dose.

Treatment:

Drug: GDC-0575

Drug: Gemcitabine

Stage 2: GDC-0575 plus Gemcitabine

Experimental group

Description:

Participants will receive GDC-0575 in combination with gemcitabine intravenously (1000 mg/m\^2 and/or 500 mg/m\^2), at or below the MTDs for the combination treatments that are determined during Stage 1.

Treatment:

Drug: GDC-0575

Drug: Gemcitabine