Evaluating the Safety and Efficacy of Chemotherapy in Patients With Relapsed Small Cell Lung Cancer in Combination With Allopurinol and MycoPhenolate (CLAMP Trial)
Overview
- Phase
- Phase 1
- Intervention
- Mycophenolate Mofetil
- Conditions
- Small-cell Lung Cancer
- Sponsor
- Washington University School of Medicine
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Number of study treatment related adverse events as measured by NCI-CTCAE v 5.0 (Phase I only)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
The hypothesis is that the addition of mycophenolate mofetil (MMF) and allopurinol to chemotherapy in patients with relapsed small cell lung cancer (SCLC) will be safely tolerated and improve outcomes, as measured by response rate and progression-free survival in patients compared to other single agent chemotherapy drugs used in historical controls.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed small cell lung cancer that has progressed on platinum-based chemotherapy and anti-PD-L1 (unless contraindicated).
- •Presence of measurable disease per RECIST 1.1 criteria
- •At least 18 years of age.
- •ECOG performance status ≤ 2
- •Normal bone marrow and organ function as defined below:
- •Absolute neutrophil count ≥ 1.5 K/cumm
- •Platelets ≥ 100 K/cumm
- •Hemoglobin ≥ 9.0 g/dL
- •Total bilirubin ≤ 1.5 x IULN
- •AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (≤ 5 x IULN for patients with liver metastases)
Exclusion Criteria
- •History of other malignancies with the exception of: (a) malignancies for which the patient has no evidence of disease at time of screening, and (b) the diagnosis is unlikely to pose a competing mortality risk in the opinion of the treating provider, and (c) for which the patient does not actively require therapy.
- •Previous intolerance to irinotecan. Treatment with prior irinotecan is allowed if the treatment was not discontinued for treatment related adverse events.
- •Unable to swallow pills or take study medications orally in accordance with administration schedule outlined
- •Currently receiving any other investigational agents. A washout period of 21 days from last dose of most recent systemic therapy to C1D1 is necessary.
- •Patients with symptomatic brain metastases are excluded. Patients with clinically evident CNS hemorrhage are excluded. Patients with brain metastases treated with whole brain radiation therapy, radiosurgery, or surgery are eligible with a washout duration from completion of radiation is 14 days. Patients treated with brain metastases that have responded to systemic therapy alone are eligible if the baseline brain MRI shows no evidence of progression. Patients with asymptomatic untreated brain metastases measuring less than 10 mm are also eligible.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to MMF, allopurinol or other agents used in the study.
- •Diarrheal illnesses such as inflammatory bowel disease that require the use of disease modifying medical therapy or steroids (patients with chronic diarrhea controlled with medications such as loperamide or diphenoxylate/atropine) are eligible if their symptoms are at baseline per discretion of treating physician and PI.
- •History of active autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis for which the patient requires active immunosuppressive therapy.
- •Pneumonitis, including organizing pneumonias related to previous treatment requiring active treatment or supplemental oxygen support.
- •Presence of active infections or patients who are not candidates for immunosuppression with MMF.
Arms & Interventions
Phase I Dose Level 1a: MMF + Irinotecan + Allopurinol
-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at 90 mg/m\^2 on Days 1 and 8. Cycles are 21 days.
Intervention: Mycophenolate Mofetil
Phase I Dose Level 1a: MMF + Irinotecan + Allopurinol
-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at 90 mg/m\^2 on Days 1 and 8. Cycles are 21 days.
Intervention: Allopurinol
Phase I Dose Level 1a: MMF + Irinotecan + Allopurinol
-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at 90 mg/m\^2 on Days 1 and 8. Cycles are 21 days.
Intervention: Irinotecan
Phase I Dose Level 1: MMF + Irinotecan + Allopurinol
-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at 100 mg/m\^2 on Days 1 and 8. Cycles are 21 days.
Intervention: Mycophenolate Mofetil
Phase I Dose Level 1: MMF + Irinotecan + Allopurinol
-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at 100 mg/m\^2 on Days 1 and 8. Cycles are 21 days.
Intervention: Allopurinol
Phase I Dose Level 1: MMF + Irinotecan + Allopurinol
-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at 100 mg/m\^2 on Days 1 and 8. Cycles are 21 days.
Intervention: Irinotecan
Phase II: MMF + Irinotecan + Allopurinol
-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at the assigned dose level on Days 1 and 8. Cycles are 21 days.
Intervention: Mycophenolate Mofetil
Phase II: MMF + Irinotecan + Allopurinol
-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at the assigned dose level on Days 1 and 8. Cycles are 21 days.
Intervention: Allopurinol
Phase II: MMF + Irinotecan + Allopurinol
-Mycophenolate mofetil (MMF) will be administered at a dose of 1 g TID (3 g/day) on a daily basis (Days 1 through 21). Allopurinol will be administered at dose of 300 mg/day on a daily basis (Days 1 through 21). Irinotecan will be given at the assigned dose level on Days 1 and 8. Cycles are 21 days.
Intervention: Irinotecan
Outcomes
Primary Outcomes
Number of study treatment related adverse events as measured by NCI-CTCAE v 5.0 (Phase I only)
Time Frame: Through 30 days after completion of treatment (estimated to be 5 months)
Overall response rate (ORR) (Phase II and phase I patients who receive the MTD)
Time Frame: Through completion of treatment (estimated to be 4 months)
* ORR is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) according to RECIST 1.1 * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Number of discontinuations due to treatment related adverse events (Phase I only)
Time Frame: Through completion of treatment (estimated to be 4 months)
Number of DLTs in Phase I patients
Time Frame: Completion of cycle 1 (each cycle is 21 days) of all enrolled Phase I participants (estimated to be 10 months)
Recommended phase II dose (RP2D) (Phase I only)
Time Frame: Completion of cycle 1 (each cycle is 21 days) of all enrolled Phase I participants (estimated to be 10 months)
-The recommended phase II dose (RP2D) is defined as the dose level at which fewer than 2 patients of a cohort of 6 patients experience dose-limiting toxicity during the first cycle.
Secondary Outcomes
- Overall survival (OS) (Phase II and phase I patients who receive the MTD)(Through 6 months after completion of treatment (estimated to be 10 months))
- Progression-free survival (PFS) (Phase II and phase I patients who receive the MTD)(Through 6 months after completion of treatment (estimated to be 10 months))