Clinical trial NCT01562275: A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0973 in Combination With GDC-0068 When Administered in Participants With Locally Advanced or Metastatic Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: GDC0973
MEK
MEK inhibitor
GDC0068
Akt
Akt inhibitor
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-03-23
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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 phosphoinositide 3-kinase (PI3K) or Akt pathway or mammalian target of rapamycin (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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (28 Days)
measure: Number of DLTs Categorized as Per the Nature
timeFrame: Cycle 1 (28 Days)
measure: Maximum Tolerated Doses (MTDs) in Combination of Cobimetinib and Ipatasertib During Dose-Escalation Stage 1
timeFrame: Cycle 1 (28 Days)
measure: Number of Participants With At Least One AE Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version (V) 4.0
timeFrame: From Baseline up to 30 days after the last dose of study treatment or until initiation of another anticancer treatment whichever occurred first (Up to 33 months)
Secondary outcomes:
measure: Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15
timeFrame: Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1
measure: Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15
timeFrame: Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1
measure: Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15
timeFrame: Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1
measure: Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15
timeFrame: Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1
measure: Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: Screening, Days 21-28 of Cycle 2, Day 25 (± 3 days) of Cycle 4 and every 8 weeks thereafter till study completion (Up to 33 months)
measure: Duration of Objective Response for Participants With Measurable Disease According to RECIST v1.1
timeFrame: Screening, Days 21-28 of Cycle 2, Day 25 (± 3 days) of Cycle 4 and every 8 weeks thereafter till study completion (Up to 33 months)
measure: Progression-Free Survival (PFS) Time for Participants With Measurable Disease According to RECIST v1.1
timeFrame: Screening, Days 21-28 of Cycle 2, Day 25 (± 3 days) of Cycle 4 and every 8 weeks thereafter till study completion (Up to 33 months)
Other outcomes:
Locations:
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Nashville
country: United States
state: Tennessee
city: Barcelona
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Shapiro GI, LoRusso P, Cho DC, Musib L, Yan Y, Wongchenko M, Chang I, Patel P, Chan IT, Sanabria-Bohorquez S, Meng RD, Bendell JC. A phase Ib open-label dose escalation study of the safety, pharmacokinetics, and pharmacodynamics of cobimetinib (GDC-0973) and ipatasertib (GDC-0068) in patients with locally advanced or metastatic solid tumors. Invest New Drugs. 2021 Feb;39(1):163-174. doi: 10.1007/s10637-020-00975-6. Epub 2020 Jul 31.