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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01907607
• Date of registration: 22/07/2013
• Prospective Registration: Yes
• Primary sponsor: Institut Bergonié
• Public title: Efficacy and Safety of PD-0332991 in Patients With Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib CYCLIGIST
• Scientific title: Efficacy and Safety of PD-0332991 in Patients With Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib: A Phase 2 Study
• Date of first enrolment: February 2014
• Target sample size: 29
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01907607
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female patients = 18 years of age

2. 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

3. CDKN2A gene deletion assessed by array-comparative genomic hybridization (array-CGH)

4. 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.

5. 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.

6. A performance status of 0, 1 or 2 according to the Eastern Cooperative Oncology Group
(ECOG) scale(Appendix 1)

7. Recovery from Grade 2 to 4 toxicity related to prior line of treatment assessed
according to NCICTCAE v.4.0 (Appendix 2)

8. Adequate bone marrow function as shown by:

Blood absolute neutrophil count (ANC) = 1.5 x 109/L

1. Blood platelets = 100 x 109/L

2. Blood hemoglobin (Hgb) > 9 g/dL

9. Adequate liver function as shown by:

c. Serum or plasma ALT and AST = 3.0 x ULN (regardless of the presence or absence of
metastases) d. Serum or plasma total bilirubin: = 1.5 x ULN (excepted for patients
with Gilbert's syndrome)

10. Adequate renal function as shown by serum creatinine = 2 x ULN

11. Patients who give a written informed consent obtained according to French and European
regulations.

12. Patients affiliated to the French Social Security

Exclusion Criteria:

1. RB1 gene deletion assessed by array-comparative genomic hybridization (array-CGH)

2. Patients who received anti-cancer drugs = 5 days prior to starting PD-0332991

3. Patients who are treated or planned to be treated concomitantly with other cytotoxic
or antineoplastic treatments, such as chemotherapy, immunotherapy, biological response
modifiers, or radiotherapy

4. Patients with another primary malignancy within 2 years prior to starting the study
drug, with the exception of adequately treated in-situ carcinoma of the uterine
cervix, or completely excised (R0 resection) basal or squamous cell carcinoma of the
skin

5. Patients with a corrected QT interval using Bazett's formula (QTcB) > 470 msec.

6. Current use or anticipated need for food or drugs that are known strong cytochrome
P450 (CYP)3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole,
itraconazole, posaconazole, erythromycin, clarithromycin, tilithromycin, indinavir,
saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir,
nefazodone, diltiazem, and delaviridine)

7. Patients with impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of PD-0332991 (e.g. severe ulcerative diseases,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or extensive (>1m)
small bowel resection, inability to swallow oral medications). Prior partial
gastrectomy is not an exclusion criterion.

8. Patients with prior complete gastrectomy

9. Any of the following in the previous 6 months: myocardial infarction, severe/unstable
angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.

10. Patients with any clinically significant medical or surgical condition which,
according to investigators' discretion, should preclude participation

1. i.e. active or uncontrolled infection, uncontrolled diabetes, active or chronic
liver disease (cirrhosis, chronic active hepatitis or chronic persistent
hepatitis)

2. hepatitis B or C virus carriers with normal liver function tests, can be included

11. Known diagnosis of human immunodeficiency virus (HIV) infection. HIV testing is not
mandatory

12. Patients who are currently receiving anticoagulation treatment with therapeutic doses
:

1. of warfarin or equivalent anticoagulant (e.g. high dose aspirin or clopidogrel or
other)

2. or have an INR >1.5. Treatment with acetylsalicyclic acid 100 mg daily or low
molecular weight heparin (LMWH) is allowed

13. Pregnant or breast-feeding women

14. Women of child-bearing potential not employing two effective methods of birth control.
Effective contraception must be used throughout the trial and 24 weeks after the end
of PD-0332991 (e.g. condom with spermicidal jelly, foam suppository or film; diaphragm
with spermicide; male condom and diaphragm with spermicide, oral, implantable, or
injectable contraceptives). Women of child-bearing potential defined as sexually
mature women who have not undergone a hysterectomy or who have not been naturally
postmenopausal for at least 12 consecutive months (i.e. who has had menses any time in
the preceding 12 consecutive months), must have a negative serum pregnancy test = 21
days prior to starting study drug.

15. Fertile males not willing to use contraception as stated above

16. Patients unwilling or unable to comply with the protocol.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Advanced Gastrointestinal Stromal Tumors

Intervention(s)

Drug: PD-0332991 will be administrated orally, formulated as gelatin capsules of 100 mg and 25 mg respectively.

Primary Outcome(s)

Efficacy assessment of PD-0332991 [Time Frame: 16 weeks]

Secondary Outcome(s)

Progression-free survival [Time Frame: 16 weeks]

Overall survival [Time Frame: 16 weeks]

Progression [Time Frame: 16 weeks]

Safety of PD-0332991 [Time Frame: 16 weeks]

Objective response [Time Frame: 16 weeks]

Secondary ID(s)

IB 2013-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors