Trial of Single Agent Sunitinib for Patients With Chemo-refractory Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01216657
Recruitment Status : Terminated (slow recruitment)
First Posted : October 7, 2010
Last Update Posted : June 4, 2013
Information provided by (Responsible Party):
Krankenhaus Nordwest

Brief Summary:
Sunitinib is a novel small molecule receptor tyrosine kinase inhibitor with direct antitumor effects as well as antiangiogenetic activity. Preclinical and clinical data for Sunitinib and data about angiogenesis and growth regulation in melanoma suggest the activity of Sunitinib in melanoma. This study will investigate the efficacy, safety and tolerability of Sunitinib as palliative treatment in chemo-refractory metastatic melanoma.

Condition or disease Intervention/treatment Phase
Chemo-refractory Melanoma Drug: Sunitinib Phase 2

Detailed Description:

This is a single agent 2-step phase 2 study with a one-year follow-up to evaluate the antitumor activity of Sunitinib administered in treatment cycles of 6 weeks duration (4 weeks treatment and 2 weeks rest) in patients with chemo-refractory melanoma. If the first step shows sufficient efficacy and tolerability the study will continue to step 2. Treatment will continue for 9 months or until disease progression or until intolerable adverse events occur. Subsequently the patients will be followed up for 1 year. Tumor assessment will be performed at baseline, at the end of cycle 1,2,3 and subsequently at the end of every uneven cycle (5,7,9,…).

A total of 40 patients will be enrolled in this trial.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Uncontrolled Phase II Trial of Single Agent Sunitinib (SU 11248) for Patients With Chemo-refractory Metastatic Melanoma
Study Start Date : March 2009
Actual Primary Completion Date : May 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
U.S. FDA Resources

Arm Intervention/treatment
Experimental: sunitinib
50 mg Sunitinib daily for 4 weeks, then 2 weeks without treatment
Drug: Sunitinib
50 mg oral, daily, for 4 weeks, then 2 weeks without treatment, repeat at d43

Primary Outcome Measures :
  1. clinical benefit rate cycle 1-3 [ Time Frame: tumor assessment every 6 weeks ]
    clinical benefit rate defined as a CR + PR + SD > 4 months duration

  2. clinical benefit rate cycle 4 and more [ Time Frame: tumor assessment every 12 weeks ]
    clinical benefit rate defined as a CR + PR + SD > 4 months duration

Secondary Outcome Measures :
  1. response rate cycle 1-3 [ Time Frame: tumor assessment every 6 weeks ]
    response rate defined as CR+PR

  2. progression free survival [ Time Frame: follow-up one year ]
  3. overall survival [ Time Frame: follow-up for one year ]
  4. response rate cycle 4 and more [ Time Frame: every 12 weeks ]
    response rate defined as CR+PR

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male and female patients aged 18 years and older.
  • Diagnosis of unresectable (Stage III) or metastatic (Stage IV), histologically or cytologically proven, melanoma without clinically meaningful surgical or radiotherapeutical options except for mucosal or ocular origin of the primary tumor.
  • Subjects must have completed a first or second line chemotherapy or be progressed under chemotherapeutic treatment. The previous treatment must have included DTIC alone or in combination
  • Performance status of 0 to 2 on the ECOG scale
  • Life expectancy > 12 weeks.
  • Patients must be able to swallow Sunitinib capsules.
  • Evidence of measurable disease according to the RECIST criteria
  • Prior radiation therapy allowed if completed at least 2 weeks and any major surgery allowed if completed at least 4 weeks prior to first dose of Sunitinib.
  • Resolution of all acute toxic side effects of prior therapy or surgical procedures to grade < 1 NCI-CTC (except for laboratory values).
  • Adequate organ function including the following:

    • platelets > 100 x 109/L
    • hemoglobin > 8 g/dl
    • absolute neutrophils count (AGC) > 1.5 x 109/L.
  • Hepatic:

    • bilirubin <=1.5 times upper limit of normal (ULN)
    • aspartate transaminase (AST) and alanine transaminase (ALT) <=2.5 times normal (AST and ALT <=5.0 times normal is acceptable if liver function abnormalities are due to underlying malignancy).
  • INR < 1.5 or a PTT within normal limits.
  • Subjects must not have any evidence of a bleeding diathesis.
  • Renal:

    • Serum creatinine < 1.5 x ULN
    • serum calcium < 1.2 mg/dl.
  • Pancreatic:
  • Serum lipase and amylase within normal range.
  • Signed and dated informed consent

Exclusion Criteria:

  • Prior treatment with ras-raf-MEK-ERK signaling pathway inhibitors (including trastuzumab, sorafenib, farnesyl transferase inhibitors or MEK inhibitors), or treatment with drugs which target VEGF (such as bevacizumab).
  • Radiotherapy, except palliative radiotherapy during study participation as described.
  • Known active infection (i.e. HIV, chronic hepatitis B or C, at the discretion of the investigator)
  • History of organ allograft or stem cell transplantation.
  • Coexisting second malignancy (excluding basal or squamous cell carcinoma of the skin, superficial bladder cancer and in situ carcinoma of the cervix with no evidence of recurrence) or history of prior malignancy
  • Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (> hemicolectomie or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis.
  • Current history of chronic diarrhea defined as persisting diarrhea for more than 3 weeks at study entry due to any reason.
  • Any of the following events prior to starting the trial treatment: *clinically evident congestive heart failure, as defined by New York Health Association (NYHA) > class II

    • Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
    • Atrial fibrillation of any grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females.
  • Subjects on beta-blockers and digoxin must be monitored closely
  • QT-interval > 450 msec
  • Risk factors for torsade-de-pointes-tachycardia (i.e.. Hypokalaemia, congenital Long-QT-syndrome)
  • Active coronary artery disease or ischemia (myocardial infarction within the last 6 months prior to study entry)
  • Coronary/peripheral artery bypass graft
  • Cerebrovascular accident or transient ischemic attack
  • Active disseminated intravascular coagulation, or history of clinically significant bleeding within the past 6 months, including gross hemoptysis or haematuria, or underlying coagulopathy
  • Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).
  • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with trial participation or trial drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.
  • Participation in any other clinical trial within the last 3 weeks.
  • Pregnant or lactating women.
  • Known allergic/hypersensitivity reaction to any of the components of the treatment, or known drug abuse/alcohol abuse.
  • Active CNS metastatic or meningeal tumors.
  • Patients with seizure disorders requiring medication (such as antiepileptics, the use of carbamazepine, phenytion an phenobarbital is prohibited).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01216657

Krankenhaus Nordwest
Frankfurt/Main, Germany, 60488
Sponsors and Collaborators
Krankenhaus Nordwest
Principal Investigator: Elke Jäger, Prof. Dr. Krankenhaus Nordwest

Responsible Party: Krankenhaus Nordwest Identifier: NCT01216657     History of Changes
Other Study ID Numbers: S379 SUMA
First Posted: October 7, 2010    Key Record Dates
Last Update Posted: June 4, 2013
Last Verified: June 2013

Keywords provided by Krankenhaus Nordwest:

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors