Phase I, Dosage-finding and PK Study of IV Topotecan and Erlotinib With Refractory Solid Tumors
Condition: Metastatic Solid Tumor
MeSH terms: Neoplasms
Intervention: Topotecan; Erlotinib
Intervention description: All subjects receive treatment with intravenous topotecan and oral erlotinib.; All subjects receive treatment with intravenous topotecan and oral erlotinib.
Intervention MeSH terms: Erlotinib Hydrochloride; Topotecan
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this research study is to determine the best dose of the combination of two
      approved drugs, intravenous topotecan and oral erlotinib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histologically confirmed malignancy that is metastatic or
             unresectable and for which standard curative or palliative measures do not exist or
             are no longer effective.

          -  Prior chemotherapy must have been completed at least 3 weeks prior to enrollment (6
             weeks for nitrosureas and mitomycin) and the patient must have recovered from all
             associated toxicities (except alopecia and neuropathy grade 1 according to the
             NCI-CTC, version 3.0 classification). Radiation must have been completed 8 weeks prior
             to enrollment. Major surgery must have been completed 4 weeks prior to enrollment.
             Hormonal therapy must have been completed at least 2 weeks prior.

          -  Age >18 years.

          -  ECOG performance status <1 (Karnofsky >70%)

          -  Life expectancy of greater than 12 weeks.

          -  Patients must have normal organ and marrow function as defined below: White blood cell
             count >2,500/mm3, Absolute neutrophil count (ANC) >1,500/ mm3, Platelet count
             >100,000/ mm3, Hemoglobin > 10 g/dL, Albumin >2.5 g/dL, Total bilirubin <1.5 X
             institutional upper limit of normal (ULN), AST/ALT <1.5 X institutional ULN, Serum
             creatinine <2.0 g/dL, Creatinine clearance >40 mL/min

          -  Patients must be able to swallow and retain oral medication

          -  Female patients must be nonpregnant and nonlactating. All patients of childbearing
             potential must implement an effective method of contraception during the study. All
             female patients (except those who are postmenopausal or surgically sterilized) must
             have a negative pre-study serum or urine pregnancy test obtained within 7 days of
             study enrollment.

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines.

        Exclusion Criteria:

          -  Patients may not be receiving any other investigational agents. Participation in other
             clinical trials with any investigational drugs must have been completed ≥ 28 days
             prior to enrollment on this trial (or longer based on the halflife of the
             investigational agent).

          -  Patients must have no more than 3 prior lines of therapy. The patient may have only
             received carboplatin and/or gemcitabine in one of the prior lines of therapy.

          -  Patients must not be receiving concurrent cancer therapy (chemotherapy, radiation
             therapy, immunotherapy, biologic therapy, hormonal therapy for cancer). Low dose
             maintenance steroids are acceptable if the patient will remain on a stable dose during
             cycles 1, 2 and 3 (to ensure continuity for topotecan pharmacokinetic studies).

          -  Patient may not have a history of serious allergic reactions attributed to compounds
             of similar chemical composition to topotecan (camptothecins) and/or erlotinib
             (tyrosine kinase inhibitors).

          -  Patients must not have malabsorption syndrome, any disease significantly altering
             gastrointestinal function, or resection of the stomach or small bowel.

          -  Patients must not be taking warfarin (including low dose anticoagulants).

          -  Patients must not be taking concurrent treatment with potent inhibitors of cytochrome
             P450 3A4. For patients who were receiving treatment with such agents, a one-week
             washout period is required prior to beginning the protocol.

          -  Patients must not be taking concurrent treatment with potent inducers of cytochrome
             P450 3A4, such as phenytoin, carbamazepine, rifampin, barbiturates, or St. John's
             Wort. For patients who were receiving treatment with such agents, a one week washout
             period is required prior to beginning the protocol.

          -  Patients must have no active serious infection, fever > 38.2 degrees Celsius, or other
             serious underlying medical condition that would otherwise impair their ability to
             receive protocol treatment (i.e., documented HIV infection, uncontrolled hypertension,
             uncontrolled CNS metastases, unstable angina, congestive heart failure, poorly
             controlled diabetes, coronary angioplasty within 6 months, myocardial infarction
             within 6 months, uncontrolled atrial or ventricular arrhythmias).

          -  Patients should not have psychological, familial, sociological geographical conditions
             that do not permit medical follow-up and compliance with the study protocol.