A Phase I Study of Indenoisoquinolines LMP400 and LMP776 in Adults With Relapsed Solid Tumors and Lymphomas

Inclusion Criteria

• •Patients must have histologically documented (confirmed at the Laboratory of Pathology, NCI), relapsed solid tumor malignancy or Hodgkin s disease/non-Hodgkin lymphoma that is metastatic or unresectable for which standard curative measures do not exist, or are associated with minimal patient survival benefit.
• •Patients must have measurable or evaluable disease.
• •Patients must have recovered to at least eligibility levels due to adverse events (AEs) and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy or biologic therapy within 4 weeks (6 weeks for nitrosoureas and mitomycin C, or 2 months for UCN-01), or therapy with tyrosine kinase inhibitors within 5 times the half-life of the inhibitors prior to entering the study. Patients must be (Bullet)2 weeks since any investigational agent administered as part of a Phase 0 study (also referred to as an early Phase I study or pre-Phase I study where a sub-therapeutic dose of drug is administered) at the PI s discretion, and should have recovered to eligibility levels from any toxicities.
• •Patients must have recovered to at least a Grade less than or equal to toxicity eligibility levels due to adverse events (AEs) and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy or biologic therapy within 4 weeks (6 weeks for nitrosoureas and mitomycin C, or 2 months for UCN-01), or therapy with tyrosine kinase inhibitors within 5 times the half-life of the inhibitors prior to entering the study. Patients must be greater than or equal to 2 weeks since any prior administration of study drug in an exploratory IND/Phase 0 study. Patients must be greater than or equal to 1 month since completion of any prior radiation (greater than or equal to 2 weeks for palliative radiation therapy). However, patients receiving bisphosphonates for any cancer or undergoing androgen deprivation therapy for prostate cancer are eligible for this therapy. Prior therapy with topoisomerase I inhibitors is allowed.
• •Age greater than or equal to 18 years.
• •The Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
• •Life expectancy greater than 3 months.
• •Patients must have normal or adequate organ and marrow function as defined below:
• •* Absolute neutrophil count greater than or equal to 1,500/microL
• •* Platelets greater than or equal to 100,000/microL
• •* Total bilirubin\* within less than or equal to 1.5 normal institutional limits
• •* AST (SGOT)/ALT (SGPT) less than or equal to 2.5 times institutional upper limit of normal
• •* Creatinine less than 1.5 times upper limit of normal
• •OR
• •Creatinine clearance greater than or equal to 60 mL/minute for patients with (measured) creatinine levels greater than or equal to 1.5 times upper limit of normal
• •\*we will allow patients with Gilbert s syndrome with total bilirubin up to 2.5 mg/dL
• •* The effects of indenoisoquinolines on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry, for the duration of study participation, and for 2 months after discontinuation from the study. Women of child bearing potential must have a negative pregnancy test in order to be eligible. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk to nursing infants secondary to treatment of the mother with indenoisoquinolines, breastfeeding should be discontinued if the mother is treated with indenoisoquinolines.
• •* Willingness to undergo skin biopsies.
• •* At the point when tumor biopsies become mandatory rather than optional, disease amenable to biopsy and willingness to undergo biopsies or patient will be undergoing a procedure due to medical necessity during which the tissue may be collected, or tumor biopsy tissue from a previous research study or medical care is available for submission at registration. Criteria for the submission of tissue are:
• •Tissue must have been collected within 3 months prior to registration
• •Patient has not received any intervening therapy for their cancer since the collection of the tumor sample
• •Tumor tissue must meet the minimum requirements outlined in Section 9.1.
• •* Ability to understand and the willingness to sign a written informed consent document.