A Phase 1 Study in Patients With Solid Tumors

• Number of participants with clinically significant effects [ Time Frame: Baseline to study completion ] [ Designated as safety issue: Yes ]
• Number of participants with a tumor response [ Time Frame: Baseline to study completion ] [ Designated as safety issue: No ]
• Pharmacokinetics, concentration maximum (Cmax) [ Time Frame: Cycle 1, Cycle 2 ] [ Designated as safety issue: No ]
• Pharmacokinetics, Area under the curve (AUC) [ Time Frame: Cycle 1, Cycle 2 ] [ Designated as safety issue: No ]

The primary objective of this study is to determine the MTD regimen for the combination therapy of LY573636 and pemetrexed that may be safely administered to patients with a solid tumor that is not amenable to curative therapy.

• Drug: LY573636

  Individualized dose is dependent on patients height, weight, gender and is adjusted to target a specific exposure range corrected for a patient's laboratory parameters. Intravenous dosing is completed once in a 28 day cycle.

  Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion are met.

  Other Name: Tasisulam
• Drug: Pemetrexed

  375-500 mg/m2, intravenous dosing is completed once each 28 day cycle.

  Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion are met.

  Other Names:

  • LY231514
  • Alimta

• Experimental: Pemetrexed followed by LY573636
  Pemetrexed on Day 1 followed by LY573636 on Day 4
  Interventions:

  • Drug: LY573636
  • Drug: Pemetrexed
• Experimental: LY573636 followed by Pemetrexed
  LY573636 on Day 1, Pemetrexed on Day 4
  Interventions:

  • Drug: LY573636
  • Drug: Pemetrexed

Inclusion Criteria:

• You must have a diagnosis of a solid tumor malignancy that is not amenable to curative therapy
• You must have a serum albumin level greater than or equal to 3.0 g/dL (30 g/L)
• You must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• You must be reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures
• Patients with reproductive potential should use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drugs
• Your test results assessing the function of your blood, kidneys, liver, and heart are satisfactory
• You must be willing to take folic acid, vitamin B12 or prophylactic steroids
• You must able to interrupt the use of aspirin (other than an aspirin dose less than or equal to 1.3 grams per day) and/or other nonsteroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents, such as piroxicam).
• You must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, hormone therapy, or other investigational therapy for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy (except alopecia). Patients who have received whole-brain radiation must wait 90 days before starting study therapy.
• You must sign an informed consent

Exclusion Criteria:

• You cannot have received other investigational drugs within the last 30 days
• You cannot have other on-going serious illnesses including active bacterial, fugal, or viral infections
• You cannot require regular, periodic paracentesis or thoracentesis
• You cannot have active brain metastasis
• You cannot currently be receiving warfarin (Coumadin®) therapy
• You cannot be pregnant or lactating
• You cannot have received prior Pemetrexed or LY573636
• You cannot have a second primary malignancy that could affect interpretation of the study results