Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (28424962)
Authors Aspeslagh S, Shailubhai K, Bahleda R, Gazzah A, Varga A, Hollebecque A, Massard C, Spreafico A, Reni M, Soria JC
Title Phase I dose-escalation study of milciclib in combination with gemcitabine in patients with refractory solid tumors.
Journal Cancer chemotherapy and pharmacology
Vol 79
Issue 6
Date 2017 Jun
URL
Abstract Text This phase I trial evaluated the safety and tolerability of milciclib, an inhibitor of multiple cyclin-dependent kinases and tropomycin receptor kinase A, in combination with gemcitabine in patients with refractory solid tumors.Sixteen patients were enrolled and treated with milciclib at three dose levels (45 mg/m2/day, n = 3; 60 mg/m2/day, n = 3; and 80 mg/m2/day, n = 10) with a fixed dose of gemcitabine (1000 mg/m2/day). Milciclib was administered orally once daily for 7 days on/7 days off in a 4-week cycle, and gemcitabine was administered intravenously on days 1, 8 and 15 in a 4-week cycle.All 16 enrolled patients were evaluable for safety and toxicity. Dose-limiting toxicities, which occurred in only one out of nine patients treated at the maximum dose tested (milciclib 80 mg/m2/day and gemcitabine 1000 mg/m2/day), consisted of Grade 4 thrombocytopenia, Grade 3 ataxia and Grade 2 tremors in the same patient. Most frequent treatment-related AEs were neutropenia and thrombocytopenia. Among 14 evaluable patients, one NSCLC patient showed partial response and 4 patients (one each with thyroid, prostatic, pancreatic carcinoma and peritoneal mesothelioma) showed long-term disease stabilization (>6-14 months). Pharmacokinetics of the orally administered milciclib (~t1/2 33 h) was not altered by concomitant treatment with gemcitabine.The combination treatment was well tolerated with manageable toxicities. The recommended phase II dose was 80 mg/m2/day for milciclib and 1000 mg/m2/day for gemcitabine. This combination treatment regimen showed encouraging clinical benefit in ~36% patients, including gemcitabine refractory patients. These results support further development of combination therapies with milciclib in advanced cancer patients.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Milciclib PHA-848125AC|PHA-848125|PHA 848125 CDK1 Inhibitor 13 CDK2 Inhibitor 19 CDK4 Inhibitor 12 CDK5 Inhibitor 7 CDK7 Inhibitor 13 TrkA Receptor Inhibitor 8 Milciclib (PHA-848125AC) is a TRKA inhibitor with additional activity against CDK1, CDK2, CDK4, CDK5, and CDK7, potentially resulting in decreased tumor cell growth (PMID: 22160853, PMID: 28424962).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown lung non-small cell carcinoma not applicable Gemcitabine + Milciclib Phase I Actionable In a Phase I trial, the combination therapy of Gemzar (gemcitabine) and Milciclib (PHA-848125AC) resulted in a clinical benefit in 36% (5/14) of patients with an advanced solid tumor, including long-term stable disease (6-14 months) in four patients and a partial response in a patient with non-small cell lung carcinoma (PMID: 28424962). 28424962
Unknown unknown Advanced Solid Tumor not applicable Gemcitabine + Milciclib Phase I Actionable In a Phase I trial, the combination therapy of Gemzar (gemcitabine) and Milciclib (PHA-848125AC) resulted in a clinical benefit in 36% (5/14) of patients with an advanced solid tumor, including long-term stable disease (6-14 months) in four patients and a partial response in a patient with non-small cell lung carcinoma (PMID: 28424962). 28424962