A Study Evaluating the Safety and Tolerability of GDC-0068 in Patients With Refractory Solid Tumors

An Open-Label, Phase I, Dose-Escalation Study Evaluating the Safety and Tolerability of GDC-0068 in Patients With Refractory Solid Tumors

This is an open-label, multicenter, Phase I study to evaluate the safety, tolerability, and pharmacokinetics of escalating oral doses of GDC-0068 administered to patients with incurable, locally advanced or metastatic solid malignancy that has progressed or failed to respond to at least one prior regimen or for which there is no standard therapy. This study is expected to enroll approximately 39 to 57 patients at approximately two sites in Spain.

Study Overview

• Status: Completed
• Conditions: Solid Cancers
• Intervention / Treatment: Drug: GDC-0068

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
  • Valencia, Spain, 46010

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically documented, incurable, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable.
• Evaluable or measurable disease
• Life expectancy >= 12 weeks
• Adequate hematologic and organ function within 14 days before initiation of GDC-0068
• Documented willingness to use an effective means of contraception (e.g., abstinence, hormonal or double barrier method, surgically sterilized partner) for both men and women while participating in the study

Exclusion Criteria:

• History of Type 1 or 2 diabetes mellitus requiring regular medication
• Grade > 2 hypercholesterolemia or hypertriglyceridemia
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Leptomeningeal disease as the only manifestation of the current malignancy
• Known untreated malignancies of the brain or spinal cord, or treated brain metastases that are not radiographically stable for >= 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: GDC-0068; Oral repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of adverse events by NCI CTCAE grade and associated dose of GDC-0068	Through study completion or early study discontinuation
Occurrence of dose-limiting toxicities (DLTs) by NCI CTCAE grade and associated dose of GDC-0068	Through study completion or early study discontinuation
Occurrence of Grade 3 or 4 abnormalities in safety-related laboratory parameters and associated dose of GDC-0068	Through study completion or early study discontinuation
PK parameters after single and multiple doses of GDC-0068	Through study completion or early study discontinuation

Secondary Outcome Measures

Outcome Measure	Time Frame
Best overall response, duration of objective response, and progression-free survival (PFS) for patients with measurable disease according to RECIST	Through study completion or early study discontinuation

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Premal Patel, M.D., Ph.D., Genentech, Inc.

Publications and helpful links

General Publications

• Malhi V, Budha N, Sane R, Huang J, Liederer B, Meng R, Patel P, Deng Y, Cervantes A, Tabernero J, Musib L. Single- and multiple-dose pharmacokinetics, potential for CYP3A inhibition, and food effect in patients with cancer and healthy subjects receiving ipatasertib. Cancer Chemother Pharmacol. 2021 Dec;88(6):921-930. doi: 10.1007/s00280-021-04344-9. Epub 2021 Sep 1.
• Saura C, Roda D, Rosello S, Oliveira M, Macarulla T, Perez-Fidalgo JA, Morales-Barrera R, Sanchis-Garcia JM, Musib L, Budha N, Zhu J, Nannini M, Chan WY, Sanabria Bohorquez SM, Meng RD, Lin K, Yan Y, Patel P, Baselga J, Tabernero J, Cervantes A. A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors. Cancer Discov. 2017 Jan;7(1):102-113. doi: 10.1158/2159-8290.CD-16-0512. Epub 2016 Nov 21. Erratum In: Cancer Discov. 2018 Nov;8(11):1490.
• De Mattos-Arruda L, Weigelt B, Cortes J, Won HH, Ng CKY, Nuciforo P, Bidard FC, Aura C, Saura C, Peg V, Piscuoglio S, Oliveira M, Smolders Y, Patel P, Norton L, Tabernero J, Berger MF, Seoane J, Reis-Filho JS. Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle. Ann Oncol. 2014 Sep;25(9):1729-1735. doi: 10.1093/annonc/mdu239. Epub 2014 Jul 9. Erratum In: Ann Oncol. 2018 Nov 1;29(11):2268.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: March 19, 2010
• First Submitted That Met QC Criteria: March 22, 2010
• First Posted (Estimate): March 23, 2010

Study Record Updates

• Last Update Posted (Estimate): July 4, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: PAM4743g; GO01335 (Other Identifier: Hoffmann-La Roche); 2009-015060-34 (EudraCT Number)