Study of Sunitinib in Young Patients with a rare type of cancer of the stomach and bowel.

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2015/03/005609
• Date of registration: 05-03-2015
• Prospective Registration: Yes
• Primary sponsor: Pfizer Limited
• Public title: Study of Sunitinib in Young Patients with a rare type of cancer of the stomach and bowel.
• Scientific title: A Phase I/II Study of Sunitinib In Young Patients with Advanced Gastrointestinal Stromal Tumor
• Date of first enrolment: 12-11-2015
• Target sample size: 30
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=11194
• Study type: Interventional
• Study design: Single Arm Trial; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Open Label
• Phase: Phase 1/ Phase 2

Countries of recruitment

Argentina, Austria, Canada, Chile, Czech Republic, Egypt, France, Germany, Hungary, India, Italy, Mexico, Norway, Poland, Portugal, Singapore, Slovakia, Spain, Turkey, United Kingdom, United States of America

Contacts

• Name: Swapnali Raut
• Affiliation: Pfizer Limited

• Name: Swapnali Raut
• Affiliation: Pfizer Limited

Key inclusion & exclusion criteria

Inclusion criteria: Patients must meet all of the following inclusion criteria to be eligible for to commence study drug treatment into the study.

1. Histological diagnosis of GIST

2. Tumor tissue must be available to assess KIT, PDGFRA, and BRAF genotypes (for any of these genes where genotyping was not previously performed) and to assess succinate dehydrogenase (SDH) protein expression by immunohistochemistry.

3. Patients must have demonstrated disease progression or intolerance to imatinib mesylate; have GIST with non-mutant KIT (tumor genotyping may be performed prior to or during screening; patients with an indeterminate KIT genotype are eligible if genotyping performed during screening); or cannot obtain imatinib in their country.

4. Age 6 to <21 years;

5. Advanced, unresectable GIST for which there are no available options for treatment with curative intent as assessed by the investigator

6. Measurable (per Response Evaluation Criteria in Solid Tumors; RECIST version 1.1; or evaluable disease

7. Resolution of all acute toxic effects of prior cancer treatment, radiotherapy or surgical procedure to NCI CTCAE v4.0 grade <=1;

8. ECOG Performance Status 0 -2 (for patients >=11 years of age) or Lansky >=50% (for patients <11 years);

9. Adequate organ function determined within 14 days prior to enrollment, defined by:

• Peripheral absolute neutrophil count (ANC) >=1500/μL;

• Platelet count >= 100,000/μL;

• Hemoglobin >= 10 g/dL;

• Total bilirubin <=1.5 x upper limit of normal (ULN) for age;

• ALT (SGPT) or AST (SGOT) <= 3 x ULN for age;

• Serum albumin >= 2.0 g/dL;

• Serum amylase and lipase <1.5 x ULN;

• Serum creatinine based on age/gender as follows:

Age Maximum Serum Creatinine (mh/dL)

Male Female

6 to <10 years 1 1

10 to <13 years 1.2 1.2

13 to <16 years 1.5 1.4

>=16 years 1.7 1.4



The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.

• Blood Pressure (BP) < the 95th percentile for age, height and gender

• Cardiac shortening fraction or ejection fraction greater than the lower limit of normal (LLN).

10. Evidence of a personally signed and dated informed consent (and where applicable, assent) document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study;

11. Patients (including legal guardian for minors where applicable) who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures, including anticipated ability to swallow capsules;

12. Male and female patients of childbearing potential who are sexually active must agree to use a highly effective method of contraception throughout the study and for 30 days after the last sunitinib treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.


Exclusion criteria: 1. Current treatment with another investigational agent and/or systemic anti-cancer therapy within 4 weeks before starting sunitinib treatment.

2. Prior sunitinib treatment;

3. Prior therapy with known risk for cardiovascular complications, eg, high intensity anthracycline therapy (ie, total equivalent cumulative dose 100 mg/m2 of doxorubicin) or prior radiation therapy that included the heart (cardiac silhouette) and/or craniospinal radiation;

4. Concomitant treatment with any drug having proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide);

5. Prior diagnosis of cardiac disease, including, but not limited to:

• Ongoing cardiac dysrhythmias of NCI CTCAE v4.0 >= grade 2, atrial fibrillation of any grade;

• QTc interval 450 msec for males or 470 msec for females;

• Hypertension that cannot be controlled by medications;

• Any of the following within the 12 months prior to starting study treatment: congestive heart failure, cerebrovascular accident including transient ischemic attack or pulmonary embolism.

6. Grade >=3 hemorrhage within 4 weeks prior to first dose of study drug

7. Current treatment with therapeutic doses of coumarin-derivative anticoagulants such as warfarin or anti-vitamin K agents;

8. Concurrent administration of strong cytochrome P450-3A (CYP3A4) inhibitor(s) and/or inducer(s) within 7 and 12 days prior to first dose of study drug, respectively;

9. Prior radiation to 25% of the bone marrow.

10. Patients with history of allergic reaction attributed to any component of sunitinib capsules;

11. Pregnant females; breastfeeding females; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for 30 days after last dose of investigational product; in the UK, males and females of childbearing potential not using two (2) methods of highly effective contraception or not agreeing to continue two (2) methods of highly effective contraception for 30 days after last dose of investigational product;

12. Active infection with HIV, or receiving antiretroviral therapy for HIV disease;

13. Patients who are investigational site staff members or relatives of those site staff members or patients who are Pfizer employees directly involved in the conduct of the trial;

14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Advanced Gastrointestinal Stromal Tumor

Intervention(s)

Intervention1: Sutent (Sunitinib malate; sponsor code SU011248).: The sunitinib intended starting dose will be 15 mg/m2/day (not to exceed 50 mg/day. Intra-patient dose escalation of sunitinib will be allowed after completion of Cycle 1. Dose escalation will be in increments of 7.5 mg/m2, up to a maximum dose of 30 mg/m2 (not to exceed 50 mg/day). A cycle of therapy is considered to be 42 days, with the reporting period for each cycle being Day 1 to Day 42. For all patients, sunitinib will be dosed intermittently [4 weeks on study drug followed by 2 weeks off therapy. In the absence of progressive disease, patients may receive up to 18 cycles of sunitinib therapy for up to 24 months, so maximum duration of treatment according to the protocol is 2 years.
Control Intervention1: Nil: Nil

Primary Outcome(s)

Pharmacokinetic parameters of sunitinib and its main active metabolite (SU012662) including total plasma exposure (AUC24) and oral clearance (CL/F).Timepoint: Descriptive statistics for observed and dose-corrected (where appropriate) PK data will be reported for all patients with at least one PK observation by presenting the population size, arithmetic mean, standard deviation, percent coefficient of variation (CV%), median, minimum, maximum values at the end of the study.

Secondary Outcome(s)

Objective response rate, duration of response, PFS and OS at 2 years after study enrollmentTimepoint: At the end of study

Type, incidence, severity (graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0 [v4.0]), timing, seriousness, and relatedness of adverse events and laboratory abnormalities;Timepoint: At the end of study

Pharmacokinetic-pharmacodynamic relationships with respect to safety and efficacy in pediatric GISTTimepoint: At the end of study

Secondary ID(s)

A6181196 Amendment 1 dated 11 June 2012

Source(s) of Monetary Support

Pfizer Limited, Pfizer Centre, Patel Estate, Off S. V. Road, Jogeshwari West, Mumbai 400 102, India

Secondary Sponsor(s)

Pfizer Limited

Ethics review

Status: Approved
Approval date: 14/01/2015
Contact:

Institutional Review Board, Rajiv Gandhi Cancer Institute & Research Center, Sec -V, Rohini, Delhi-110085, India

Status: Not Approved
Approval date:
Contact:

Ethics Committee on Clinical Trials, lndraprastha Apollo Hospitals, Sarita Vihar, Delhi - Mathura Road, New Delhi - 110076, India

Status: Not Approved
Approval date:
Contact:

Institutional Review Board I & II, Main Building 3rd Floor, Tata Memorial Hospital, Dr. Ernest Borges Road, Parel. Mumbai-400012, Maharashtra. India

Results

• Date Completed: 30/06/2016