• Tumor responses to EC145 therapy. [ Time Frame: Duration of EC145 therapy will vary according to individual patient response. ] [ Designated as safety issue: No ]
• Progression-free survival, response duration, and overall survival time observed after EC145 therapy. [ Time Frame: 2 years after completing therapy with EC145 and the 30-day follow-up period. ] [ Designated as safety issue: No ]

• Tumor responses to EC145 therapy. [ Time Frame: Duration of EC145 therapy will vary according to individual patient response. ]
• Time-to-progression, response duration, and overall survival time observed after EC145 therapy. [ Time Frame: 2 years after completing therapy with EC145 and the 30-day follow-up period. ]

This is a Phase II clinical trial evaluating the benefit from therapy with EC145 in patients with progressive adenocarcinoma of the lung.

This is a Phase II clinical trial of EC145 administered to patients with progressive adenocarcinoma of the lung.

EC145 is a drug that is specifically designed to enter cancer cells via the folate vitamin receptor (FR). Experimental evidence shows that this target receptor is expressed on a significant portion of non-small cell lung cancers. Early clinical evidence in a small number of Phase I patients suggests that EC145 is generally well-tolerated, without many of the side-effects observed in more-standard therapeutic agents. This evidence suggests that EC145 may be useful as a chemotherapy against progressive adenocarcinomas of the lung. The primary objective of this study is to collect data on clinical benefit produced by therapy with EC145.

All patients will undergo imaging with the FR targeting investigational imaging agent EC20 (FolateScan) during the screening period to confirm eligibility for the treatment portion of the clinical trial. Clinical evidence suggests that EC20 may be used to identify patients with cancers that express the target receptor.

Information about the safety and tolerability of both EC145 and EC20 will be assessed.

Induction phase of treatment: Two 4-week cycles; if stable disease or better at (week 8) CT, patient may proceed into maintenance phase.

Maintenance phase of treatment: 4-week cycles with CT every 8 weeks. Patients continue on study until they experience disease progression, unacceptable toxicity, or attain protocol-defined maximum benefit.

Inclusion Criteria:

• Advanced, progressive, adenocarcinoma of the lung.
• Previously received at least 2 cytotoxic containing chemotherapeutic regimens (can include an EGFR inhibitor). There is no upper limit to the number of prior chemotherapeutic regimens.
• ECOG performance status of 0-2.
• At least 4 weeks from prior therapy and recovered from associated acute toxicities.
• Radiographic evidence of measurable disease and EC20 "positive" tumor.
• Adequate bone marrow reserve, hepatic, and renal function.
• Negative serum pregnancy test for women of childbearing potential and willingness to practice contraceptive methods.

Exclusion Criteria:

• Serious comorbidities (as determined by the Principal Investigator).
• History of carcinomatous peritonitis.
• History of severe bowel obstruction (as determined by the Principal Investigator).
• Women who are pregnant or lactating.
• Prior radiation therapy to assessable disease, unless disease progression is confirmed at that site.
• Patients requiring palliative radiotherapy at time of study entry.

Note: Patients with CNS metastasis are eligible if a) they have been treated for the CNS metastasis and have been clinically stable (with regard to their CNS disease) for >4 weeks and b) they do not require steroids or antiseizure medications (i.e., for seizure control), or if the CNS metastasis has been untreated to date, it is not associated with a midline shift or significant edema and there is no clinically-evident requirement for steroids or antiseizure medication. In either situation, patients must be off steroids and/or antiseizure medications for at least 14 days.