Sunitinib or Cediranib for Alveolar Soft Part Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01391962
First received: July 9, 2011
Last updated: June 5, 2014
Last verified: December 2013

July 9, 2011
June 5, 2014
June 2011
June 2015   (final data collection date for primary outcome measure)
  • Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Determine the ORR of cediranib in patients who progress on thesunitinib arm, and determine the ORR of sunitinib in patients whoprogress on the cediranib arm [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01391962 on ClinicalTrials.gov Archive Site
  • Determine the progression-free survival (PFS) at 24 weeks in Part I and in Part II of the study for single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. [ Time Frame: 4 and 6 months ] [ Designated as safety issue: No ]
  • Perform pharmacokinetic analysis for cediranib [ Time Frame: At the time of progression ] [ Designated as safety issue: No ]
Determine the progression-free survival (PFS) at 6 months in Part I and in Part II of the study for single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Sunitinib or Cediranib for Alveolar Soft Part Sarcoma
A Phase II Trial In Which Patients With Metastatic Alveolar Soft Part Sarcoma Are Randomized to Either Sunitinib or Cediranib Monotherapy, With Cross-Over at Disease Progression

Background:

- Alveolar soft part sarcoma is a rare type of tumor that has a lot of blood vessel growth. Cediranib and sunitinib are two cancer treatment drugs that work by blocking the growth of new blood vessels. This may help to stop tumor growth. Some patients with alveolar soft part sarcoma treated with cediranib or sunitinib had tumors that either decreased in size or remained stable without growth for a long time. More research is needed to see whether these drugs can be approved as a standard treatment for alveolar soft part sarcoma.

Objectives:

  • To test the safety and effectiveness of cediranib and sunitinib to treat alveolar soft part sarcoma.
  • To determine the objective response rate of cediranib and sunitinib in patients with alveolar soft part sarcoma.

Eligibility:

  • Individuals at least 16 years of age who have alveolar soft part sarcoma.
  • Individuals who have not received prior cediranib or sunitinib.

Design:

  • All participants will be screened with a physical exam and medical history. They will also have blood and urine tests, tumor imaging studies, and biopsies.
  • Participants will be divided into two groups: one group will start with cediranib and the other will start with sunitinib.
  • During Part I of the study, participants will take cediranib or sunitinib by mouth once a day. They will continue this routine every day for 28 days (one cycle of treatment). They will stop taking the drug if the side effects become too severe or the tumor starts growing again.
  • Participants will not have any cancer treatment for 2 weeks before starting Part II.
  • During Part II, participants will receive the other study drug (cediranib or sunitinib). However, if one of the drugs is not effective or its side effects are too severe, participants will not receive the drug and will stop being in the study.
  • Participants will be monitored with frequent blood and urine tests. They will also have tumor imaging studies and other tests.

Background:

  • Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets.
  • Cediranib (AZD2171) and sunitinib (SU011248), oral small molecule inhibitors of VEGF receptor tyrosine kinases, are showing preliminary evidence of activity in patients with ASPS.

Objectives:

  • Part I: Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS.
  • Part II: Determine the ORR of cediranib in patients who progress on the sunitinib arm, and determine the ORR of sunitinib in patients who progress on the cediranib arm.
  • Determine the progression-free survival (PFS) at 24 weeks for single-agent cediranib and

single-agent sunitinib malate in patients with advanced ASPS.

Eligibility:

  • Patients age greater than or equal to 16 years with histologically or cytologically confirmed metastatic ASPS.
  • Patients must show evidence of objective disease progression per RECIST 1 on scans within the 3-month period immediately preceding enrollment. Both scans used to determine disease progression should have been obtained within this 6-month period.
  • Patients must not have received treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed.

Design:

  • Part I: Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles.
  • Part II: At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period.
  • Appropriate anatomic imaging studies will be performed at baseline and every 2 cycles for restaging.
  • The study will be conducted using an optimal two-stage design to rule out an unacceptably low 15% clinical response rate (PR+CR) in favor of a modestly high response rate of 40%.

The study will initially enroll 10 evaluable patients in each arm. If 0 or 1 of the 10 patients has a clinical response, then no further patients will be accrued. If 2 or more the first 10 patients have a response, then accrual continues to a total of 22 patients in each arm.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Sarcoma, Alveolar Soft Part
  • Drug: Cediranib
    30 mg orally, once daily, in 28 day cycles
  • Drug: Sunitinib
    37.5 mg orally, once a day, in 28-day cycles
  • Experimental: Part I
    Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles
    Interventions:
    • Drug: Cediranib
    • Drug: Sunitinib
  • Experimental: Part II
    At the time of disease progression patients will cross over to the other treatment arm after a 2-week wash-out period.
    Interventions:
    • Drug: Cediranib
    • Drug: Sunitinib

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
47
April 2016
June 2015   (final data collection date for primary outcome measure)
  • INCLUSION CRITERIA:

Status Update: Patients enrolled after Amendment G (version dated 08/16/2013), will be evaluated and compared to the first 13 patients by the study statistician and the Principal Investigator.

  • Patients must have histologically confirmed metastatic alveolar soft part sarcoma that is not curable by surgery. Diagnosis of malignancy must be confirmed by the department of pathology at the institution where the patient is enrolled prior to patient enrollment.
  • Patients must show evidence of objective disease progression per RECIST 1 on scans at least 6 weeks apart within the 3-month period immediately preceding enrollment.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT scan.
  • Any prior therapy must have been completed greater than or equal to 4 weeks prior to enrollment on protocol and the participant must have recovered to eligibility levels from prior toxicity. Patients should be at least 6 weeks out from nitrosoureas and mitomycin C. Prior radiation should have been completed greater than or equal to 4 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels. Patients who have had prior monoclonal antibody therapy must have completed that therapy at least 3 half-lives of the antibody or 6 weeks ago. Patients who have received more than a cumulative dose of 350 mg/m(2) of doxorubicin may be enrolled at the discretion of the Coordinating Center PI after consultation with a cardiologist and if screening echocardiogram is normal.
  • Patients must be greater than or equal to 2 weeks since any investigational agent administered as part of a Phase 0 study (also referred to as an early Phase I study or pre-Phase I study where a sub-therapeutic dose of drug is administered) at the Coordinating Center PI s discretion, and should have recovered to eligibility levels from any toxicities.
  • Patients with no prior therapy are eligible, provided they have metastatic disease that is not curable by surgery.
  • Age greater than or equal to 16 years. Patients age 16-17 years are eligible only if they have a BSA greater than or equal to 1.7 m(2) or weigh greater than or equal to 60 kg.
  • ECOG performance status less than or equal to 2.
  • Life expectancy of greater than 3 months.
  • Patients must have normal organ and marrow function as defined below:

    • leukocytes greater than or equal to 3,000/mcL
    • absolute neutrophil count greater than or equal to 1,500/mcL
    • platelets greater than or equal to 100,000/mcL
    • hemoglobin greater than or equal to 9 g/dL
    • total serum bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
    • creatinine within normal institutional limits

OR

  • creatinine clearance greater than or equal to 60 mL/min for patients with creatinine levels above institutional normal

    • QTc < 480 msec (with Bazett s correction) in screening electrocardiogram.
    • The following groups of patients are eligible after consultation with a cardiologist and at the Coordinating Center PI s discretion, provided they have New York Heart Association Class II (NYHA) cardiac function on baseline ECHO/MUGA:
  • those with a history of Class II heart failure who are asymptomatic on treatment
  • those with prior anthracycline exposure greater than a cumulative dose of 350 mg/m(2)
  • those who have received central thoracic radiation that included the heart in the radiotherapy port.

    • Patients must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility. Initiation or adjustment of BP medication is permitted prior to study entry provided that the BP reading prior to enrollment is no greater than 140/90 mmHg.
    • Left ventricular ejection fraction (LVEF) greater than or equal to institutional lower limit of normal.
    • Because sunitinib is metabolized primarily by the CYP3A4 liver enzyme, strong CYP3A4 inhibitors are not permitted within 7 days before and during the study, and strong CYP3A4 inducers are not permitted within 12 days before and during the study. Every effort should be made to switch patients taking such agents or substances to other medications 1 week prior to starting therapy, particularly patients with brain metastases who are taking enzyme-inducing anticonvulsant agents. Patients who require potent CYP3A4 inducers or inhibitors and cannot switch medications must have their case reviewed by the Coordinating Center PI and may be enrolled only after discussion with, and agreement from the Coordinating Center PI. Current clinical studies with cediranib have not found clinically significant effects on cediranib PK with coadministration of CYP3A4 inducers or inhibitors. Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics (PK) of cediranib will be determined following review of their case by the Coordinating Center PI.
    • Both study agents have been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling. For this reason, women of childbearing potential must have a negative pregnancy test prior to study entry. Women of child-bearing potential and men must agree to use two reliable forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 2 months following study drug discontinuation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
    • Patients who are nursing infants: because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated with the study agents.
    • Ability to understand and the willingness to sign a written informed consent document.
    • Patients must be able to swallow whole tablets and capsules.

EXCLUSION CRITERIA:

  • Patients must not have received prior treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed.
  • Patients may not be receiving any other investigational agents.
  • Major surgery within 4 weeks prior to entry into the study, or a surgical incision that is not fully healed.
  • History of familial long QT syndrome, or use of medications that may cause QTc interval prolongation.
  • Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible.
  • Warfarin and its derivatives are not allowed. Patient can be receiving low molecular weight heparin if clinically indicated.
  • Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow, retain, and/or absorb the drug are excluded.
  • Patients with any of the following conditions are excluded: serious or non-healing wound, ulcer; history of abdominal fistula, gastrointestinal perforation, or intra -abdominal abscess within 28 days of treatment; coronary/peripheral artery bypass graft or stenting within the past 12 months; or cerebrovascular accident (CVA) or transient ischemic attack within the past 12 months.
  • Greater than 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart or 24-hour urine protein of > 1 g. Patients with < 2+ proteinuria are eligible following initial determination by urinalysis within 1 week prior to enrollment and do not need the urinalysis repeated.
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions with cediranib or sunitinib. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Both
16 Years and older
No
Contact: Deborah E Allen, R.N. (301) 402-5640 allendeb@mail.nih.gov
Contact: Shivaani Kummar, M.D. (301) 435-0517 kummars@mail.nih.gov
United States,   Canada
 
NCT01391962
110200, 11-C-0200
Not Provided
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Shivaani Kummar, M.D. National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP