Efficacy and Safety of PD-0332991 in Patients With Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib (CYCLIGIST)

Efficacy and Safety of PD-0332991 in Patients With Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib (CYCLIGIST)

Gastrointestinal Stromal Tumor

Ongoing, but not recruiting

2

Start Date 08/01/2013

Age of Trial (yrs) 11.3

Gleevec-resistant

Cdk4 & Cdk6 inhibitor

Block related tumor signal paths

Specifically GIST and only GIST

CYCLIGIST IB 2013-01 CSET 2090

Institut Bergonié NCI France funding

Oral

See ClinicalTrials.gov Links (NCT#) for full site info.

This is a multicentre single-arm Phase II study evaluating the efficacy and safety of orally PD-0332991, 125 mg/day, 21 days on/7 days off, in patients with documented disease progression while on therapy with 2nd line sunitinib for unresectable and/or metastatic GIST. Indeed, the usual treatment for advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib is best supportive care for which outcome data are already available (Demetri et al., 2012; Italiano et al., 2012). Sixty three patients will be included in 10 centres of the French Sarcoma Group over a period of 18 months of enrolment.

Patients will be evaluated at scheduled visits in up to three study periods:

Pre-treatment (PRE TT): from signature of informed consent to the first treatment by PD-0332991.
Treatment (TT): from the first treatment by PD-0332991 to the first 28 days following the last PD-0332991 administration.
Follow-up (FUP): after treatment discontinuation, all patients must be followed up for 28 days after the last dose of the study drug for safety assessment (AEs and/or SAEs).

Inclusion Criteria (partial):

Male or female patients ≥ 18 years of age
Histologically confirmed GIST of any anatomical location and confirmed by the RRePS Network ; positive immunohistochemical staining for c-KIT (CD117); or negative staining for KIT, but with either positive staining for DOG1 or an identified mutation of KIT or PDGFRA gene
CDKN2A gene deletion assessed by array-comparative genomic hybridization (array-CGH)
Unresectable and/or metastatic disease with documented progression according to modified RECIST criteria (see section 7.2.1.5 of protocol) after 1st line imatinib and 2nd line sunitinib. Progression on the last line of treatment should be confirmed by central review with two radiological assessments identical (CT scans or MRI) obtained at less from 4 months interval within the 24 months before inclusion.
At least one measurable GIST lesion according to RECIST (v1.1 Appendix 3). A previously irradiated lesion is eligible to be considered as a measurable lesion provided that there is objective evidence of progression of the lesion prior to starting PD-0332991.

Patients affiliated to the French Social Security

Exclusion Criteria (partial): Patienst with prior complete gastrectomy. RB1 gene deletion assessed by array-comparative genomic hybridization (array-CGH)