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

An Open-label, Uncontrolled Phase II Trial of Single Agent Sunitinib (SU 11248) for Patients With Chemo-refractory Metastatic Melanoma

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.

Study Overview

• Status: Terminated
• Conditions: Chemo-refractory Melanoma
• Intervention / Treatment: Drug: Sunitinib

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
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Frankfurt/Main, Germany, 60488
    • Krankenhaus Nordwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical benefit rate cycle 1-3	clinical benefit rate defined as a CR + PR + SD > 4 months duration	tumor assessment every 6 weeks
clinical benefit rate cycle 4 and more	clinical benefit rate defined as a CR + PR + SD > 4 months duration	tumor assessment every 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
response rate cycle 1-3	response rate defined as CR+PR	tumor assessment every 6 weeks
progression free survival		follow-up one year
overall survival		follow-up for one year
response rate cycle 4 and more	response rate defined as CR+PR	every 12 weeks

Collaborators and Investigators

• Sponsor: Krankenhaus Nordwest
• Investigators: Principal Investigator: Elke Jäger, Prof. Dr., Krankenhaus Nordwest

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: April 12, 2010
• First Submitted That Met QC Criteria: October 6, 2010
• First Posted (Estimate): October 7, 2010

Study Record Updates

• Last Update Posted (Estimate): June 4, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: sunitinib; melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: S379 SUMA