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

NCT ID: NCT01564251

Last Updated: 2020-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-23
• Study Completion Date: 2018-01-11

Brief 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.

Conditions

Lymphoma, Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stage 1 Arm 1: GDC-0575 Monotherapy

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.

Group Type: EXPERIMENTAL

GDC-0575

Intervention Type: DRUG

Participants will receive GDC-0575 orally at a starting dose of 15 mg.

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

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.

Group Type: EXPERIMENTAL

GDC-0575

Intervention Type: DRUG

Participants will receive GDC-0575 orally at a starting dose of 15 mg.

Gemcitabine

Intervention Type: DRUG

Participants will receive gemcitabine intravenously at a dose of 1000 mg/m\^2 and/or 500 mg/m\^2.

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

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.

Group Type: EXPERIMENTAL

GDC-0575

Intervention Type: DRUG

Participants will receive GDC-0575 orally at a starting dose of 15 mg.

Gemcitabine

Intervention Type: DRUG

Participants will receive gemcitabine intravenously at a dose of 1000 mg/m\^2 and/or 500 mg/m\^2.

Stage 2: GDC-0575 plus Gemcitabine

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.

Group Type: EXPERIMENTAL

GDC-0575

Intervention Type: DRUG

Participants will receive GDC-0575 orally at a starting dose of 15 mg.

Gemcitabine

Intervention Type: DRUG

Participants will receive gemcitabine intravenously at a dose of 1000 mg/m\^2 and/or 500 mg/m\^2.

Interventions

GDC-0575

Participants will receive GDC-0575 orally at a starting dose of 15 mg.

Intervention Type: DRUG

Gemcitabine

Participants will receive gemcitabine intravenously at a dose of 1000 mg/m\^2 and/or 500 mg/m\^2.

Intervention Type: DRUG

Other Intervention Names

RO6845979; Gemzar

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

Yale Cancer Center

New Haven, Connecticut, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

The Sarah Cannon Research Inst

Nashville, Tennessee, United States

Institut Bergonie; Oncologie

Bordeaux, , France

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, , France

Countries

United States; France

References

Italiano A, Infante JR, Shapiro GI, Moore KN, LoRusso PM, Hamilton E, Cousin S, Toulmonde M, Postel-Vinay S, Tolaney S, Blackwood EM, Mahrus S, Peale FV, Lu X, Moein A, Epler J, DuPree K, Tagen M, Murray ER, Schutzman JL, Lauchle JO, Hollebecque A, Soria JC. Phase I study of the checkpoint kinase 1 inhibitor GDC-0575 in combination with gemcitabine in patients with refractory solid tumors. Ann Oncol. 2018 May 1;29(5):1304-1311. doi: 10.1093/annonc/mdy076.

Reference Type: DERIVED

PMID: 29788155 (View on PubMed)

Other Identifiers

2011-005602-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GP28153

Identifier Type: -

Identifier Source: org_study_id