A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0973 in Combination With GDC-0068 When Administered in Patients With Locally Advanced or Metastatic Solid Tumors

This study is currently recruiting participants.
Verified April 2014 by Genentech
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01562275
First received: March 21, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

This open-label, multicenter, Phase Ib dose-escalation study will evaluate the safety, tolerability and pharmacokinetics of oral dosing of GDC-0973 and GDC-0068 administered in combination in patients with locally advanced or metastatic solid tumors. Cohorts of patients will receive multiple ascending doses of GDC-0973 and GDC-0068. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.


Condition Intervention Phase
Neoplasms
Drug: GDC-0973
Drug: GDC-0068
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of GDC-0973 and GDC-0068 in Patients With Locally Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Incidence of dose-limiting toxicities [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Nature of dose-limiting toxicities [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Estimation of the maximum tolerated dose [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Nature of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Incidence of serious adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Nature of serious adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Severity of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Severity of serious adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters of GDC-0973 and GDC-0068: total exposure [ Time Frame: Days 1, 8, and 15 pre-dose and up to 24 h post-dose for Cycle 1 and Day 1 on Cycles 2 and 3 ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of GDC-0973 and GDC-0068: maximum plasma concentration [ Time Frame: Days 1, 8, and 15 pre-dose and up to 24 h post-dose for Cycle 1 and Day 1 on Cycles 2 and 3 ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of GDC-0973 and GDC-0068: minimum concentration [ Time Frame: Days 1, 8, and 15 pre-dose and up to 24 h post-dose for Cycle 1 and Day 1 on Cycles 2 and 3 ] [ Designated as safety issue: No ]
  • Objective response for patients with measurable disease according to RECIST criteria [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Duration of objective response for patients with measurable disease according to RECIST criteria [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]
  • Progression-free survival for patients with measurable disease according to RECIST criteria [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 108
Study Start Date: April 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: GDC-0973
multiple doses
Drug: GDC-0068
multiple doses
Experimental: B Drug: GDC-0973
multiple doses
Drug: GDC-0068
multiple doses

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically documented locally advanced or metastatic solid tumors for which standard therapies either do not exist or have proven ineffective or intolerable
  • Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST)
  • Life expectancy >/= 12 weeks
  • Adequate hematologic and end organ function

Exclusion Criteria:

  • History of prior significant toxicity from another MEK pathway inhibitor requiring discontinuation of treatment
  • History of prior significant toxicity from another PI3K or Akt pathway or mTOR inhibitor requiring discontinuation of treatment
  • Anti-cancer therapy within 28 days prior to first dose of study drug, except as stated in protocol
  • History of type I or type II diabetes mellitus requiring insulin
  • Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease)
  • Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, hepatitis B or hepatitis C virus
  • Active autoimmune disease
  • Pregnant or lactating women
  • Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
  • History of glaucoma
  • History of retinal vein occlusion
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01562275

Contacts
Contact: Reference Study ID Number: GE28079 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Recruiting
Detroit, Michigan, United States, 48201
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
Spain
Recruiting
Barcelona, Spain, 08035
Recruiting
Valencia, Spain, 46010
Sponsors and Collaborators
Genentech
Investigators
Study Director: Clinical Trials Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01562275     History of Changes
Other Study ID Numbers: GE28079
Study First Received: March 21, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech:
GDC0973
MEK
MEK inhibitor
GDC0068
Akt
Akt inhibitor

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014