A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours

NCT ID: NCT01396408

Last Updated: 2025-03-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 137 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-09
• Study Completion Date: 2025-12-31

Brief Summary

This research is being done because there is no treatment that will cure this type of cancer. Although some types of chemotherapy can cause this cancer to shrink for a time, better options are needed.

Detailed Description

The purpose of this study is to find out what effects the study drugs - sunitinib or temsirolimus - will have on this type of cancer. The study will begin by finding out if sunitinib can shrink the cancer. If sunitinib does not work, temsirolimus will be tested next.

Conditions

Advanced Rare Tumours

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sunitinib

Group Type: ACTIVE_COMPARATOR

Sunitinib

Intervention Type: DRUG

50 mg PO daily for 28 days, q 6 weeks (1 cycle=6 weeks or 42 days)

Temsirolimus

Group Type: ACTIVE_COMPARATOR

Temsirolimus

Intervention Type: DRUG

25 mg IV weekly (Days 1, 8, 15, 22, 29, 36), q 6 weeks (1 cycle=6 weeks or 42 days)

Interventions

Sunitinib

50 mg PO daily for 28 days, q 6 weeks (1 cycle=6 weeks or 42 days)

Intervention Type: DRUG

Temsirolimus

25 mg IV weekly (Days 1, 8, 15, 22, 29, 36), q 6 weeks (1 cycle=6 weeks or 42 days)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Radiation: Patients may have had prior radiation therapy. A minimum of 28 days (4 weeks) since the last dose of radiation must have elapsed prior to registration (exceptions may be made for low dose, palliative radiotherapy. Patients must have recovered from any acute toxic effects from radiation prior to registration.

Previous surgery: is permitted provided that wound healing has occurred and at least 28 days have elapsed prior to registration if surgery was major.

Laboratory Requirements:

(must be done within 7 days prior to registration) Hematology Absolute granulocytes: ≥ 1.5 x 10^9/L Platelets: ≥ 100 x 10^9/L

Chemistry:

ALL Patients Bilirubin ≤ 1.5 x UNL (upper normal limit) AST and ALT ≤ 2.5 x UNL Serum Creatinine ≤UNL or: Creatinine clearance ≥ 60ml/min

Chemistry:

TEMSIROLIMUS Arm Only Fasting cholesterol ≤ 9.0 mmol/L Fasting triglycerides ≤ 4.56 mmol/L

• Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by Cockcroft Formula: Females: GFR = 1.04 x (140-age) x weight in kg serum creatinine in μmol/L Males: GFR = 1.23 x (140-age) x weight in kg serum creatinine in μmol/L
• Patient or guardian consent must be obtained on all patients according to local Institutional and/or University Human Experimentation Committee requirements. Children > 8 years old whose parent or guardian has signed consent on their behalf may also sign assent if desired. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the NCIC CTG Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. Because of differing requirements, a standard consent form for the trial will not be provided but a sample form is provided. A copy of the initial full board REB approval and approved consent form must be sent to the central office. The patient or their parent/legal guardian must sign the consent form prior to registration. Please note that the consent form for this study must contain a statement which gives permission for the NCIC CTG and monitoring agencies to review patient records.
• Patients must be accessible for treatment, response assessment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. (Call the NCIC CTG office at 613-533-6430 if questions arise regarding the interpretation of this criterion.) Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.

In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working days of patient registration.

Ineligibility Criteria - ALL Patients

Patients who fulfill any of the following criteria are not eligible for admission to either the sunitinib treatment arm (Arm A) or temsirolimus arm (Arm B) of this study:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer or other solid tumours curatively treated with no evidence of disease for ≥ 3 years.
• Patients who have had prior treatment with relevant mTOR or VEGFR, KIT, RET, PDGFR inhibitors. Patients who have had prior treatment with mTOR inhibitors are ineligible for temsirolimus; patients who have had prior treatment with VEGFR, KIT, RET or PDGFR inhibitors are ineligible for sunitinib.
• Pregnant or lactating women. Women of childbearing potential must have a urine pregnancy test proven negative within 7 days prior to registration. Men and women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Patients with known symptomatic brain metastases (a brain CT is not necessary to rule out brain metastases, unless there is clinical suspicion of CNS involvement). Patients with treated and radiologic or clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to entry).
• Patients with known hypersensitivity to the relevant study drug or its components, or compounds of similar chemical or biologic composition.
• Patients receiving concurrent treatment with other anti-cancer therapy or other investigational agents.
• Patients with serious illness or medical condition which would not permit the patient to be managed according to the protocol including, but not limited to:

1. History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements

2. Active uncontrolled infection

3. Any other medical conditions that might be aggravated by treatment

4. Serious or non-healing wound, ulcer, or bone fracture.

5. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment. Patients believed to be at high risk for fistula formation because of the location and extent of their disease should not be enrolled.

Ineligibility Criteria - SUNITINIB Arm Only

Patients who fulfill any of the following criteria are not eligible for admission to the sunitinib treatment arm (Arm A) of this study:

• Patients with pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction as follows:

1. QTc prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant abnormalities on screening ECG (required within 14 days prior to registration).

2. Current or history of Class III or IV heart failure as defined by the NYHA functional classification system.

3. Patients with prior anthracycline exposure, previous central thoracic radiation that included heart in radiation port, or a history of NYHA Class II cardiac function UNLESS they are currently asymptomatic with respect to cardiac function AND left ventricular ejection fraction (LVEF) > lower limit of normal (LLN) of institution as assessed by screening MUGA or ECHO (required within 14 days prior to registration).

4. Poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg.

5. Myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry

6. History of pulmonary embolism within the past 12 months; patients with incidental pulmonary emboli found on routine scanning > 6 months prior to registration may be eligible.

7. History of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry.

• Patients who require use of therapeutic doses of coumadin-derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis. Use of low molecular weight heparin is permitted provided the patient's INR is ≤ 1.5. INR on screening coagulation (required within 7 days prior to registration).
• Patients with bowel obstruction or GI tract disease resulting in an inability to absorb oral medication , such as uncontrolled inflammatory GI disease (e.g. Crohn's disease, ulcerative colitis) or post surgical malabsorption characterized by uncontrolled diarrhea that results in weight loss and vitamin deficiency or requires IV hyperalimentation; or any condition that would preclude compliance with oral medication.
• Patients with pre-existing hypothyroidism are ineligible, unless they are euthyroid on medication.
• Inability to discontinue drugs known to be potent inhibitors or inducers of cytochrome P450 (CYP3A4). Patients must be off these medications 7-12 days prior to the first dose of sunitinib.

Inhibitors- prohibited 7 days before dosing and during study. azole antifungals (ketoconazole, itraconazole, miconazole, fluconazole) HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir) clarithromycin verapamil erythromycin delavirdine diltiazem nefazodone telithromycin

Inducers- prohibited 12 days before dosing and during study. rifampin phenytoin rifabutin St. John's wort carbamazepine efavirenz phenobarbital tipranavir

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hal Hirte

Role: STUDY_CHAIR

Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON Canada

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Izaak Walton Killam (IWK) Health Centre

Halifax, Nova Scotia, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

McGill University - Dept. Oncology

Montreal, Quebec, Canada

CHU Sainte-Justine

Montreal, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Countries

Canada

Other Identifiers

I206

Identifier Type: -

Identifier Source: org_study_id