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

NCT00813423 | Completed Phase 1

• 6 other identifiers: NCI-2012-03112CTEP #83420509098342P30CA072720U01CA132194
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of sunitinib malate when given together with hydroxychloroquine in treating patients with advanced solid tumors that have not responded to chemotherapy. Sunitinib malate 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. Hydroxychloroquine may help sunitinib malate work better in treating solid tumors. Giving sunitinib malate together with hydroxychloroquine may kill more tumor cells.

Conditions

Adult Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• MTD of sunitinib malate, as assessed by the NCI CTCAE version 4.0 (v4.0)

  28 days

• Response rate using the international criteria RECIST

  Reported with 95% confidence interval.

  Up to 2 years

Secondary Outcomes (6)

• Survival

  Up to 2 years

• Percent changes of the marker expressions, beclin1, LC3, p62 and GRp170, as indicators of autophagy potential in tissue

  Up to 96 hours post-dose (course 2)

• Mean number of autophagic vesicles per cell (mAV/cell) by electron microscopy (EM) as indication of flux through the autophagy pathway for non-apoptotic cells

  Up to 96 hours post-dose (course 2)

• Steady-state plasma concentration of hydroxychloroquine (HCQ)

  Up to 96 hours post-dose (course 2)

• Autophagy inhibition and PK interaction

  Up to 96 hours post-dose (course 2)

Study Arms (1)

Treatment (sunitinib malate, hydroxychloroquine)

EXPERIMENTAL

Patients receive sunitinib malate PO QD on days 1-28 and hydroxychloroquine PO QD or BID on days 1-42 (beginning day 4 of course 1). Treatment repeats every 42 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Hydroxychloroquine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sunitinib Malate

Interventions

Hydroxychloroquine DRUG

Given PO

Treatment (sunitinib malate, hydroxychloroquine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (sunitinib malate, hydroxychloroquine)

Pharmacological Study OTHER

Correlative studies

Treatment (sunitinib malate, hydroxychloroquine)

Sunitinib Malate DRUG

Given PO

Also known as: SU011248, SU11248, sunitinib, Sutent

Treatment (sunitinib malate, hydroxychloroquine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically proven advanced cancer
• Patients must have undergone treatment with at least one regimen of standard therapy, either cytotoxic chemotherapy, an oral targeted agent or immunotherapy, or have a form of cancer for which no standard therapy exists, or are not eligible for or decline standard therapy; patients who have received prior therapy with sunitinib will be allowed; patients with prostate cancer may continue on hormonal therapy if they are currently receiving it
• Patients must have measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Life expectancy \> 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL
• Serum calcium =\< 12.0 mg/dL
• Total serum bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/ananine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal, unless the patient has liver metastases, in which case both AST and ALT must be =\<5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Thyroid-stimulating hormone (TSH) within normal institutional limits is required for eligibility; free T3 and free T4 values will also be obtained for baseline values should repeat parameters be required later in the course of treatment, however these values will not be used to determine eligibility
• Creatine phosphokinase (CPK) within normal institutional limits

You may not qualify if:

• Patients must be able to understand and sign informed consent
• Patients who have had chemotherapy or radiotherapy or biologic agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; at least 4 weeks must have elapsed since any major surgery
• Patients on treatment for rheumatoid arthritis or systemic lupus erythematosus
• Patients receiving any disease-modifying anti-rheumatic drug (DMARD)
• Active clinically significant infection requiring antibiotics, antivirals or antifungals; these medications may be allowed for instances of prophylaxis or treatment felt to not be clinically significant at the discretion of the principal investigator
• Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) are ineligible
• Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible
• Diagnosis or history of central nervous system (CNS) disease (i.e. primary brain tumor, malignant seizures, untreated CNS metastases or carcinomatous meningitis or CNS metastases)
• Patient must not have ongoing ventricular cardiac dysrhythmias of grade = 2 as described by the Cancer Therapy Evaluation Program (CTEP) Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE); patients with a history of serious ventricular arrhythmia (ventricular tachycardia \[VT\] or ventricular fibrillation \[VF\] \> 3 beats in a row) are also excluded; additionally, patients with ongoing atrial fibrillation are not eligible
• Corrected QT (QTc) interval \>= 500 msec on baseline electrocardiogram (EKG)
• Any of the following within 6 months prior to first dose of treatment: 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, or pulmonary embolus
• Patients with known human immunodeficiency virus (HIV) are excluded due to possibility of unknown side effects on the immune system by these agents; the potential impact of pharmacokinetic interactions of retroviral therapy with sunitinib is unknown; appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future
• Because sunitinib is metabolized primarily by the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) liver enzyme, the eligibility of patients taking medications that are potent inducers or inhibitors of that enzyme will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications
• Must not have psoriasis or porphyria
• Must not have known hypersensitivity to 4-aminoquinoline compound

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Interventions

Hydroxychloroquine; Sunitinib

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Indoles

Study Officials

• Janice M Mehnert

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2008
• First Posted: December 23, 2008
• Study Start: February 19, 2010
• Primary Completion: July 18, 2023
• Study Completion: July 18, 2023
• Last Updated: August 2, 2023

Record last verified: 2023-07

Locations

US (2)