Hydroxychloroquine and Temozolomide in Treating Patients With Metastatic or Unresectable Solid Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00714181
• Date of registration: 11/07/2008
• Primary sponsor: University of Pennsylvania
• Public title: Hydroxychloroquine and Temozolomide in Treating Patients With Metastatic or Unresectable Solid Tumors
• Scientific title: A Phase I Study of Hydroxychloroquine in Combination With Temozolomide in Patients With Advanced Solid Tumors
• Date of first enrolment: June 2008
• Target sample size: 40
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT00714181
• Study type: Interventional
• Study design: Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Clinical Trials Office - Abramson Cancer Center of the Univers

• Name: Ravi Amaravadi, MD
• Affiliation: Abramson Cancer Center of the University of Pennsylvania

Key inclusion & exclusion criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed solid tumor

- Metastatic or unresectable disease

- Refractory to standard therapy or no standard therapy exists

- Measurable disease by RECIST criteria

- Brain metastases allowed provided patient completed radiotherapy (if radiotherapy was
clinically indicated at the time of diagnosis) AND discontinued steroids prior to
study enrollment

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- WBC = 3,000/mm³

- Absolute granulocyte count = 1,500/mm³

- Platelet count = 100,000/mm³

- Serum creatinine = 2.0 times upper limit of normal (ULN)

- Total bilirubin = 1.5 times ULN (< 3.0 times ULN in the presence of Gilbert's
disease)

- AST and ALT = 2.5 times ULN (= 5.0 times ULN in the presence of liver metastases)

- aPTT normal

- INR = 1.5 (if on anticoagulation, INR must be < 1.5 prior to starting
anticoagulation)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No porphyria

- No psoriasis, unless the disease is well controlled and patient is under the care of
a specialist who agrees to monitor the patient for exacerbations

- No previously documented macular degeneration or diabetic retinopathy

- No concurrent serious illness including, but not limited to, any of the following:

- Ongoing or active infection requiring parenteral antibiotics

- Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
myocardial infarction, or unstable angina)

- New York Heart Association class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Peripheral vascular disease = grade 2 within the past year

- Psychiatric illness/social situation that would limit compliance with study
requirements

- No other concurrent malignancies, other than basal cell skin cancer, squamous cell
skin cancer, carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ
of the breast

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from all prior therapy

- The following prior therapy is allowed in the adjuvant or metastatic disease setting:

- Immunotherapy (interferon, aldesleukin, or sargramostim [GM-CSF])

- Chemotherapy, either as a single-agent or as combination therapy

- Vaccine therapy

- Targeted or biological therapy

- Chloroquine derivatives

- At least 4 weeks since prior active immunotherapy (aldesleukin, interferon, or
ipilimumab)

- At least 4 weeks since prior chemotherapy

- At least 2 weeks since prior oral targeted therapies

- More than 4 weeks since prior and no other concurrent investigational anticancer
therapy (except for vaccines)

- No prior temozolomide

- Prior radiotherapy allowed

- If radiotherapy has been administered to a lesion, there must be radiographic
evidence of progression of that lesion in order for that lesion to constitute
measurable disease or to be included in the measured target lesions

- No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin,
carbamazepine, phenobarbital, primidone, or oxcarbazepine), rifampin, or Hypericum
perforatum (St. John's wort)

- No other concurrent anticancer therapy



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Unspecified Adult Solid Tumor, Protocol Specific

Intervention(s)

Drug: hydroxychloroquine

Drug: temozolomide

Genetic: TdT-mediated dUTP nick end labeling assay

Genetic: western blotting

Other: electron microscopy

Other: high performance liquid chromatography

Other: immunoenzyme technique

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Other: mass spectrometry

Other: pharmacological study

Primary Outcome(s)

Maximum tolerated dose of hydroxychloroquine [Time Frame: Yes]

Secondary Outcome(s)

Pharmacodynamic and pharmacokinetic correlative endpoints [Time Frame: No]

Toxicity rates [Time Frame: Yes]

Secondary ID(s)

CDR0000600329

UPCC-12907

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)