Chemotherapy in Patients With Relapsed Small Cell Lung Cancer in Combination With Allopurinol and MycoPhenolate (CLAMP Trial)

• Status: Not yet recruiting
• Trial end date: 2024-01-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Treatments: Allopurinol; Irinotecan; Mycophenolic Acid

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed small cell lung cancer that has progressed on prior systemic therapy

• 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 ≥ 1,500 K/mm3

• Platelets ≥ 100,000 K/mm3

• 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)

• Creatinine ≤ 1.5 x IULN OR measured or calculated creatinine clearance > 50 mL/min for patients with creatinine levels > 1.5 x IULN

• Use of MMF during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations (especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system). For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 6 weeks after stopping study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 90 days after last dose of study treatment. Women must not be breastfeeding.

• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• A history of other malignancy 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 as along as 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.

• Patients with untreated 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. Patients with asymptomatic brain metastases (measuring less than 10 mm) are allowed.

• A 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 requires medical therapy.

• 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, for which patients require active treatment or supplemental oxygen support.

• Active infections or those patients who are not candidates for immunosuppression with MMF.

• Undergone major surgery within 28 days prior to Cycle 1 Day 1, or minor surgery/subcutaneous venous access device placement within 7 days prior to Cycle 1 Day 1, or has elective or planned major surgery to be performed during the course of the clinical trial.

• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis at a level of Child-Pugh B or worse, cirrhosis (any degree) with a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis (defined as ascites from cirrhosis requiring diuretics or paracentesis), fatty liver, and inherited liver disease.

• Active tuberculosis.

• Severe infections within 2 weeks prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.

• Unresolved grade 2 or higher toxicities from previous treatment with the exception of fatigue, endocrine AEs that are being managed with hormone replacement, or alopecia.

• Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1 Day 1

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to C1D1.

• Active hepatitis B (chronic or acute) defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Note: Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test are eligible.

• Patients known to be HIV positive are ineligible.

• SN-38 is metabolized by CYP3A4 enzymes, and therefore patients enrolling to this study should be prohibited from use of medications known to be strong inducers or inhibitors of CYP3A4. Strong CYP3A4 inducers should be discontinued for at least 2 weeks before starting irinotecan therapy. Strong CYP3A4 inhibitors should be discontinued at least 1 week before starting irinotecan therapy.