Sunitinib and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors That Have Not Responded to Chemotherapy

Sunitinib and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors That Have Not Responded to Chemotherapy
This study is currently recruiting participants.
Verified June 2012 by University of Medicine and Dentistry New Jersey

First Received on December 20, 2008.  
Last Updated on June 12, 2012  
History of Changes
Sponsor: University of Medicine and Dentistry New Jersey
Collaborator: National Cancer Institute (NCI)
Information provided by (Responsible Party): University of Medicine and Dentistry New Jersey
ClinicalTrials.gov Identifier: NCT00813423
  Purpose

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib together with hydroxychloroquine may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of sunitinib when given together with hydroxychloroquine in treating patients with advanced solid tumors that have not responded to chemotherapy.

Condition Intervention Phase
Cancer Drug: hydroxychloroquine
Drug: sunitinib malate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Autophagic Modulation With Anti-Angiogenic Therapy in Patients With Advanced Malignancies: A Phase I Trial of Sunitinib and Hydroxychloroquine

Resource links provided by NLM:

Further study details as provided by University of Medicine and Dentistry New Jersey:

Primary Outcome Measures:

  • Maximum tolerated dose of sunitinib malate [ Time Frame: 18 months for accrual ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: 18 months for accrual ] [ Designated as safety issue: Yes ]
  • Response [ Time Frame: 18 months for accrual, response measured after every 3 cycles ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: 18 months for accrual, survival from the time of treatment start date ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: October 2010
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:

    Drug: hydroxychloroquine

    Drug will be taken according to the assigned dose for that cohort either 200 mg qd, 200 mg bid or 400 mg qam with 200 mg qpm.

    Drug: sunitinib malate

    Sunitinib will be started at a dose of 50 mg qd with escalating doses of hydroxychloroquine taken at the dose assigned to the individual cohort.

Detailed Description:

OBJECTIVES:

  • To determine the maximum tolerated dose of sunitinib malate, an oral tyrosine kinase inhibitor with antiangiogenic activity, that inhibits VEGFR2, c-kit, and PDGFR, in combination with hydroxychloroquine, an inhibitor of autophagy, in patients with advanced solid tumors that are refractory to standard chemotherapy.

OUTLINE: This is a dose-escalation study of sunitinib malate.

Patients receive oral sunitinib malate once daily and oral hydroxychloroquine twice daily on days 1-28. Treatment repeats every 42 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 1 year.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed cancer
  • Must have undergone treatment with ≥ 1 regimen of standard therapy (i.e., cytotoxic chemotherapy, an oral targeted agent, or immunotherapy)

    • Prior therapy with sunitinib malate allowed
    • Concurrent hormonal therapy for prostate cancer allowed
  • Measurable disease according to RECIST criteria
  • No diagnosis or history of CNS disease (i.e., primary brain tumor, malignant seizures, untreated CNS metastases, or carcinomatous meningitis)

    • Patients with brain metastases that have been treated and stable for > 4 weeks are allowed

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute granulocyte count > 1,500/mm³
  • Platelet count > 100,000/mm³
  • Serum creatinine < 2.0 times upper limit of normal (ULN) OR creatinine clearance > 30 mL/min
  • Total bilirubin < 1.5 times ULN
  • SGOT and SGPT < 2.5 times ULN
  • LVEF > 50% by MUGA scan
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of any condition (social or medical) that, in the opinion of the investigator, might interfere with the patient’s ability to comply with the protocol or pose additional or unacceptable risk to the patient
  • No serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient’s ability to complete the study, at the discretion of the investigator
  • No second primary malignancy, except most in situ carcinoma (e.g., adequately treated nonmelanoma carcinoma of the skin) or other malignancy treated at least 5 years previously with no evidence of recurrence
  • No active clinically significant infection requiring antibiotics
  • No hypertension that cannot be controlled by medications (diastolic BP > 100 mm Hg despite optimal medical therapy)
  • No pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be maintained in the normal range with medication
  • No ongoing grade 2 (NCI CTCAE v3.0) ventricular cardiac dysrhythmias

    • No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation > 3 beats in a row)
    • No ongoing atrial fibrillation
  • QTc interval ≤ 500 msec on baseline EKG
  • None of the following conditions within the past 6 months:

    • Myocardial infarction
    • Symptomatic coronary artery disease (severe or unstable angina)
    • Artery bypass graft
    • Uncontrolled arrhythmias
    • Symptomatic congestive heart failure
    • Cerebrovascular accident or transient ischemic attack
    • Pulmonary embolus
  • No known HIV positivity
  • No psoriasis or porphyria
  • No known prior hypersensitivity to sunitinib or hydroxychloroquine or any of their components
  • No known hypersensitivity to 4-aminoquinoline compound
  • No retinal or visual field changes from prior 4-aminoquinoline compound use
  • No known G-6P deficiency
  • No known gastrointestinal pathology that would interfere with drug bioavailability
  • No clinically significant bleeding or clotting disorder

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • More than 2 weeks since prior and no concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), St. John’s wort, ketoconazole, dexamethasone, the dysrhythmic drugs (e.g., terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice

    • Topical or inhaled steroids allowed
  • At least 4 weeks since prior treatment with cytotoxic or biologic agents (6 weeks for mitomycin C or nitrosoureas)
  • At least 4 weeks since prior surgery, radiation, hormonal therapy, or other drug therapy
  • No concurrent hydroxychloroquine for treatment or prophylaxis of malaria
  • No concurrent treatment for rheumatoid arthritis or systemic lupus erythematosus
  • No concurrent disease-modifying anti-rheumatic drug (DMARD)
  • No other concurrent investigational or commercial agents or therapies with the intent to treat the patient’s malignancy
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00813423

Locations
United States, New Jersey
The Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Office of Human Research Services     732-235-8675        
Sponsors and Collaborators
University of Medicine and Dentistry New Jersey
Investigators
Principal Investigator: Janice M. Mehnert, MD Cancer Institute of New Jersey
  More Information

Additional Information:

No publications provided

Responsible Party: University of Medicine and Dentistry New Jersey
ClinicalTrials.gov Identifier: NCT00813423    
History of Changes
Other Study ID Numbers: 050909, U01CA132194, CDR0000630334, 0220090238, CTEP #8342
Study First Received: December 20, 2008
Last Updated: June 12, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Medicine and Dentistry New Jersey:

unspecified adult solid tumor, protocol specific
recurrent breast cancer
recurrent adrenocortical carcinoma
recurrent neuroendocrine carcinoma of the skin
recurrent pheochromocytoma
recurrent parathyroid cancer
recurrent pituitary tumor
recurrent thyroid cancer
recurrent intraocular melanoma
recurrent retinoblastoma
recurrent cervical cancer
recurrent gestational trophoblastic tumor
recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor
recurrent endometrial carcinoma
recurrent vaginal cancer
recurrent vulvar cancer
recurrent anal cancer
recurrent colon cancer
recurrent rectal cancer
recurrent esophageal cancer
recurrent extrahepatic bile duct cancer
recurrent gallbladder cancer
recurrent gastric cancer
recurrent gastrointestinal carcinoid tumor
recurrent adult primary liver cancer
recurrent pancreatic cancer
recurrent small intestine cancer
recurrent extragonadal germ cell tumor
recurrent extragonadal seminoma

Additional relevant MeSH terms:

Hydroxychloroquine
Sunitinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 21, 2012

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