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. All scans to assess evaluable and/or measurable disease must have been performed within 28 days of enrollment.
• 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, ANC >1,500/ mm3, Platelet count >100,000/ mm3, HGB > 10 g/dL, Albumin >2.5 g/dL, Total bilirubin <1.5 X institutional 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.