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

Primary Purpose

Lymphoma, Solid Tumor

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GDC-0575
Gemcitabine
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Solid Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Yale Cancer Center
  • Dana Farber Cancer Institute
  • Karmanos Cancer Institute
  • University of Oklahoma Health Sciences Center
  • The Sarah Cannon Research Inst
  • Institut Bergonie; Oncologie
  • Institut Gustave Roussy; Departement Oncologie Medicale

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Stage 1 Arm 1: GDC-0575 Monotherapy

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

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

Stage 2: GDC-0575 plus Gemcitabine

Arm 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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Participants With Adverse Events (AEs)
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Maximum Tolerated Dose (MTD) of GDC-0575
Recommended Phase II Dose of GDC-0575
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of GDC-0575
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 hours (h) postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only); predose (0.5h), 2h postdose on Day 9
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Maximum Observed Plasma Concentration (Cmax) GDC-0575
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Minimum Observed Plasma Trough Concentration (Cmin) of GDC-0575
Time to Reach Maximum Observed Plasma Concentration (Tmax) of GDC-0575
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Apparent Terminal Half-Life (t1/2) of GDC-0575
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Apparent Oral Clearance (CL/F) of GDC-0575
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Accumulation Ratio (Rac) of GDC-0575
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
PK-dose Proportionality as Assessed With Cmax of GDC-0575
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
PK-dose Proportionality as Assessed With AUC of GDC-0575
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Phospho-Cyclin-Dependent Kinase 2 (pCdk2) Levels in Fresh Tumor
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3 and 10 of Cycle 2. Stage 1 Arm 2b: Screening (Day -21 to -1), Day 3 of Weeks 4 and 5. Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 1 and 2
Phospho-Cyclin-Dependent Kinase 2 (pCdk2) Levels in Skin Tissue
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3 and 10 of Cycle 2. Stage 1 Arm 2b: Screening (Day -21 to -1), Day 3 of Weeks 4 and 5. Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 1 and 2
Gamma-H2Ax (γ-H2Ax) Levels in Fresh Tumor
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3 and 10 of Cycle 2. Stage 1 Arm 2b: Screening (Day -21 to -1), Day 3 of Weeks 4 and 5. Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 1 and 2
Gamma-H2Ax (γ-H2Ax) Levels in Skin Tissue
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3 and 10 of Cycle 2. Stage 1 Arm 2b: Screening (Day -21 to -1), Day 3 of Weeks 4 and 5. Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 1 and 2

Secondary Outcome Measures

Percentage of Participants With Objective Response as Determined Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Progression-Free Survival (PFS) as Determined Using RECIST v1.1
Duration of Objective Response as Determined Using RECIST v1.1

Full Information

First Posted
March 23, 2012
Last Updated
February 22, 2020
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01564251
Brief Title
A Study of GDC-0575 Alone and in Combination With Gemcitabine in Participants With Refractory Solid Tumors or Lymphoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
March 23, 2012 (Actual)
Primary Completion Date
January 11, 2018 (Actual)
Study Completion Date
January 11, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Solid Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
104 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stage 1 Arm 1: GDC-0575 Monotherapy
Arm Type
Experimental
Arm 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.
Arm Title
Stage 1 Arm 2a: GDC-0575 + Gemcitabine (750 or 1000 mg/m^2)
Arm Type
Experimental
Arm 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.
Arm Title
Stage 1 Arm 2b: GDC-0575 plus Gemcitabine (500 mg/m^2)
Arm Type
Experimental
Arm 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.
Arm Title
Stage 2: GDC-0575 plus Gemcitabine
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
GDC-0575
Other Intervention Name(s)
RO6845979
Intervention Description
Participants will receive GDC-0575 orally at a starting dose of 15 mg.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
Participants will receive gemcitabine intravenously at a dose of 1000 mg/m^2 and/or 500 mg/m^2.
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs)
Time Frame
Baseline up to approximately 5 years
Title
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time Frame
Stage 1 Arm 1: Day 1 up to Day 21. Stage 1 Arm 2: Day 1 up to Day 22 or 29
Title
Maximum Tolerated Dose (MTD) of GDC-0575
Time Frame
Stage 1 Arm 1: Day 1 up to Day 21. Stage 1 Arm 2: Day 1 up to Day 22 or 29
Title
Recommended Phase II Dose of GDC-0575
Time Frame
Stage 1 Arm 1: Day 1 up to Day 21. Stage 1 Arm 2: Day 1 up to Day 22 or 29
Title
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) of GDC-0575
Description
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 hours (h) postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only); predose (0.5h), 2h postdose on Day 9
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose on Days 1, 2, 3, 8, 15; postdose on Days 1, 2, 3, 4, 5, 8, 15. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose and postdose on Days 2, 9 (detailed timeframe is provided in outcome measure description)
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
Description
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose on Days 1, 2, 3, 8, 15; postdose on Days 1, 2, 3, 4, 5, 8, 15. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose and postdose on Days 2, 9 (detailed timeframe is provided in outcome measure description)
Title
Maximum Observed Plasma Concentration (Cmax) GDC-0575
Description
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose on Days 1, 2, 3, 8, 15; postdose on Days 1, 2, 3, 4, 5, 8, 15. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose and postdose on Days 2, 9 (detailed timeframe is provided in outcome measure description)
Title
Minimum Observed Plasma Trough Concentration (Cmin) of GDC-0575
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes) on Day 2; predose (0.5h) on Day 9
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of GDC-0575
Description
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose on Days 1, 2, 3, 8, 15; postdose on Days 1, 2, 3, 4, 5, 8, 15. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose and postdose on Days 2, 9 (detailed timeframe is provided in outcome measure description)
Title
Apparent Terminal Half-Life (t1/2) of GDC-0575
Description
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose on Days 1, 2, 3, 8, 15; postdose on Days 1, 2, 3, 4, 5, 8, 15. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose and postdose on Days 2, 9 (detailed timeframe is provided in outcome measure description)
Title
Apparent Oral Clearance (CL/F) of GDC-0575
Description
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose on Days 1, 2, 3, 8, 15; postdose on Days 1, 2, 3, 4, 5, 8, 15. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose and postdose on Days 2, 9 (detailed timeframe is provided in outcome measure description)
Title
Accumulation Ratio (Rac) of GDC-0575
Description
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose on Days 1, 2, 3, 8, 15; postdose on Days 1, 2, 3, 4, 5, 8, 15. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose and postdose on Days 2, 9 (detailed timeframe is provided in outcome measure description)
Title
PK-dose Proportionality as Assessed With Cmax of GDC-0575
Description
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose on Days 1, 2, 3, 8, 15; postdose on Days 1, 2, 3, 4, 5, 8, 15. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose and postdose on Days 2, 9 (detailed timeframe is provided in outcome measure description)
Title
PK-dose Proportionality as Assessed With AUC of GDC-0575
Description
Stage 1 Arm 1, Cycle 1 of 21 days: predose (5 to 30 minutes) on Days 1, 2, 3, 8, 15; 0.5, 1, 1.5, 2, 4, 6, 8 h postdose on Days 1, 3; 2, 4h postdose on Days 2, 15; 2h postdose on Day 8; on Days 4, 5. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose (5 minutes), 0.5, 1, 1.5, 2, 4, 6h postdose on Day 2 (additionally at 8h postdose on Day 2 for Arm 2a only) ; predose (0.5h), 2h postdose on Day 9
Time Frame
Stage 1 Arm 1, Cycle 1 of 21 days: predose on Days 1, 2, 3, 8, 15; postdose on Days 1, 2, 3, 4, 5, 8, 15. Stage 1 Arm 2 and Stage 2, Cycle 1 of 21 days: predose and postdose on Days 2, 9 (detailed timeframe is provided in outcome measure description)
Title
Phospho-Cyclin-Dependent Kinase 2 (pCdk2) Levels in Fresh Tumor
Description
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3 and 10 of Cycle 2. Stage 1 Arm 2b: Screening (Day -21 to -1), Day 3 of Weeks 4 and 5. Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 1 and 2
Time Frame
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3, 10 of Cycle 2. Stage1 Arm2b, Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 4, 5 (Stage1 Arm2b), Weeks 1, 2 (Stage 2)
Title
Phospho-Cyclin-Dependent Kinase 2 (pCdk2) Levels in Skin Tissue
Description
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3 and 10 of Cycle 2. Stage 1 Arm 2b: Screening (Day -21 to -1), Day 3 of Weeks 4 and 5. Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 1 and 2
Time Frame
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3, 10 of Cycle 2. Stage1 Arm2b, Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 4, 5 (Stage1 Arm2b), Weeks 1, 2 (Stage 2)
Title
Gamma-H2Ax (γ-H2Ax) Levels in Fresh Tumor
Description
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3 and 10 of Cycle 2. Stage 1 Arm 2b: Screening (Day -21 to -1), Day 3 of Weeks 4 and 5. Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 1 and 2
Time Frame
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3, 10 of Cycle 2. Stage1 Arm2b, Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 4, 5 (Stage1 Arm2b), Weeks 1, 2 (Stage 2)
Title
Gamma-H2Ax (γ-H2Ax) Levels in Skin Tissue
Description
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3 and 10 of Cycle 2. Stage 1 Arm 2b: Screening (Day -21 to -1), Day 3 of Weeks 4 and 5. Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 1 and 2
Time Frame
Stage 1 Arm 1: Screening (Day -21 to -1), Cycle 1 Day 4 (Cycle length=21 days). Stage 1 Arm 2a: Screening (Day -21 to -1), Days 3, 10 of Cycle 2. Stage1 Arm2b, Stage 2: Screening (Day -21 to -1), Day 3 of Weeks 4, 5 (Stage1 Arm2b), Weeks 1, 2 (Stage 2)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Objective Response as Determined Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame
Baseline until disease progression or death (up to approximately 5 years)
Title
Progression-Free Survival (PFS) as Determined Using RECIST v1.1
Time Frame
Baseline until disease progression or death (up to approximately 5 years)
Title
Duration of Objective Response as Determined Using RECIST v1.1
Time Frame
Baseline until disease progression or death (up to approximately 5 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
The Sarah Cannon Research Inst
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Institut Bergonie; Oncologie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Institut Gustave Roussy; Departement Oncologie Medicale
City
Villejuif
ZIP/Postal Code
94805
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
29788155
Citation
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.
Results Reference
derived

Learn more about this trial

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

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