Phase 1
Completed N=48
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
Neoplasms
Source: ClinicalTrials.gov NCT01562275 ↗
Enrolled (actual)
48
Serious AEs
40.9%
Results posted
Mar 2016
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities (DLTs) — 0; 0; 0; 0 participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of DLTs Categorized as Per the Nature |
— | — |
| PRIMARY Maximum Tolerated Doses (MTDs) in Combination of Cobimetinib and Ipatasertib During Dose-Escalation Stage 1 |
60; 200; 150; 300 | — |
| PRIMARY 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 |
4; 15; 36; 1; 10 | — |
| SECONDARY 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 |
688; 538; 1760; 2170; 255; 956 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 |
137; 97.1; 300; 336; 42.9; 156 | — |
| SECONDARY Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 |
1.03; 1.02; 1.00; 1.04; 1.00; 3.04 | — |
| SECONDARY Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 |
6.18; 6.07; 23.7; 25.1; 4.32; 13.4 | — |
| SECONDARY 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) |
0; 0; 0; 1; 1; 0 | — |
| SECONDARY Duration of Objective Response for Participants With Measurable Disease According to RECIST v1.1 |
— | — |
| SECONDARY Progression-Free Survival (PFS) Time for Participants With Measurable Disease According to RECIST v1.1 |
— | — |
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
Data sourced from ClinicalTrials.gov (NCT01562275). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.