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

This study has been terminated.
(slow recruitment)
Sponsor:
Information provided by (Responsible Party):
Krankenhaus Nordwest
ClinicalTrials.gov Identifier:
NCT01216657
First received: April 12, 2010
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Chemo-refractory Melanoma
Drug: Sunitinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Krankenhaus Nordwest:

Primary Outcome Measures:
  • clinical benefit rate cycle 1-3 [ Time Frame: tumor assessment every 6 weeks ] [ Designated as safety issue: No ]
    clinical benefit rate defined as a CR + PR + SD > 4 months duration

  • clinical benefit rate cycle 4 and more [ Time Frame: tumor assessment every 12 weeks ] [ Designated as safety issue: No ]
    clinical benefit rate defined as a CR + PR + SD > 4 months duration


Secondary Outcome Measures:
  • response rate cycle 1-3 [ Time Frame: tumor assessment every 6 weeks ] [ Designated as safety issue: No ]
    response rate defined as CR+PR

  • progression free survival [ Time Frame: follow-up one year ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: follow-up for one year ] [ Designated as safety issue: No ]
  • response rate cycle 4 and more [ Time Frame: every 12 weeks ] [ Designated as safety issue: No ]
    response rate defined as CR+PR


Enrollment: 7
Study Start Date: March 2009
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01216657

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

No publications provided

Responsible Party: Krankenhaus Nordwest
ClinicalTrials.gov Identifier: NCT01216657     History of Changes
Other Study ID Numbers: S379 SUMA
Study First Received: April 12, 2010
Last Updated: June 3, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Krankenhaus Nordwest:
melanoma
sunitinib

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

ClinicalTrials.gov processed this record on August 28, 2014