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

Phase 2
16 Years
Open (Enrolling)
Advanced Rare Tumours

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Trial Information

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

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

Inclusion Criteria

Eligibility Criteria - ALL Patients

Patients must have histologically or cytologically confirmed diagnosis of a rare tumour as

1. Vascular sarcomas: Angiosarcoma, hemangiosarcoma, hemangiopericytoma,

2. Clear cell carcinomas of the ovary, endometrium;

3. Medullary thyroid carcinoma;

4. Tumours of neuroendocrine origin not arising from the pancreas: paragangliomas,
pheochromocytoma (excludes carcinoid, atypical carcinoid, merkel cell, pancreatic
islet tumours and other small cell carcinomas as activity in carcinoids, small cell
lung and islet tumours already evaluated in disease specific phase 2 trials);

5. Adrenocorticocarcinoma;

6. Thymic carcinoma;

7. Fibrolamellar hepatocellular carcinoma;

8. Exploratory genetic cohort 1: other rare invasive cancers arising from identified
somatic mutations in VEGFR, PDGFR, KIT, RET;

9. Exploratory genetic cohort 2: invasive and incurable malignancies arising in patients
with known or suspected germline mutations in PTEN, TS1/2, LKB1, neurofibromatosis 1
or 2;

10. Unspecified cohort for exploratory evaluation. The unspecified histologies must also
be rare tumours for which there are no traditional phase II clinical trials and for
which there are clinical activity or laboratory data to support the likely
sensitivity to the agents. Please call NCIC CTG for consultation prior to

- Patients must have unresectable, locally advanced or metastatic disease for
which there are no known life prolonging standard therapies.

- Patients must have tumour tissue from their primary tumour available.

- Presence of clinically and/or radiologically documented disease. Chest x-ray -
≥20 mm Ct scan (with slice thickness of ≤ 5 mm) - ≥ 10 mm Longest diameter
Physical exam (using calipers) ≥ 10 mm Lymph nodes by ct scan ≥ 15 mm Measured
in short axis

- All radiology studies must be performed within 21 days prior to registration
(within 28 days if negative).

- ≥ 16 years.

- Patients must have a life expectancy of at least 12 weeks.

- ECOG performance status 0, 1 or 2.

- Previous Therapy


Patients may have received prior chemotherapy (no limit on number of prior regimens),
however no prior treatment with relevant mTOR or VEGFR, KIT, RET, PDGFR inhibitors is
permitted (i.e. to be eligible for sunitinib: no prior treatment with VEGFR, KIT, RET
or PDGFR inhibitors permitted; to be eligible for temsirolimus: no prior treatment
with mTOR inhibitors permitted). A minimum of 28 days (4 weeks) must have elapsed
since the last dose of chemotherapy prior to registration. Patients must have
recovered from any treatment related toxicities prior to registration.


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

Previous Surgery:

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 109/L Platelets: ≥ 100 x 109/L


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


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

* 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

- Patient consent must be obtained according to local Institutional and/or
University Human Experimentation Committee requirements. 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 although a sample form will be provided. A copy of the
initial full board REB approval and approved consent form must be sent to the
central office. The patient 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

- 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. 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 fulfil 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

Ineligibility Criteria - SUNITINIB Arm Only

Patients who fulfil 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 (see Appendix VI).

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

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective Response

Outcome Description:

Objective response as assessed by RECIST version 1.1 criteria as a 30% decrease in the sum of the longest diameters of the target lesions (partial response) maintained for at least 4 weeks, or complete disappearance of disease and cancer related symptoms (complete response), also maintained for at least 4 weeks. Early progression is defined as progressive disease at or prior to the first assessment. The 95% confidence interval for response rate will be calculated. The median and range of the duration of response will be assessed

Outcome Time Frame:

Every 4 weeks

Safety Issue:



Canada: Health Canada

Study ID:




Start Date:

July 2011

Completion Date:

July 2015

Related Keywords:

  • Advanced Rare Tumours