Details

Details

Title A Phase 1 Study of [14C]-MLN9708 to Assess Mass Balance, Pharmacokinetics, and Metabolism in Patients with Advanced Solid Tumors or Lymphoma

IRB MLNM1Y12

CC 13-1017

Hospital Main Campus

Phase Phase 1

Disease Lymphoma, Lymphoma - Hodgkin, Lymphoma - Non - Hodgkin, Solid Tumors

Description

Description

Primary Objectives
  • To assess the mass balance (ie, cumulative excretion of total radioactivity in urine and feces) of MLN9708 following a single dose of 4.0-mg [14C]-MLN9708 oral solution containing approximately 500 nCi of total radioactivity in patients with advanced solid tumors or lymphoma in Part A
  • To characterize the pharmacokinetics of MLN9708 in plasma and urine, and of total radioactivity in plasma and whole blood following a single dose of 4.0-mg [14C]-MLN9708 in Part A
Secondary Objectives
  • To collect samples for characterization of the metabolic profile of MLN9708 in plasma, urine, and feces following a single dose of 4.0-mg [14C]-MLN9708 in Part A
  • To assess the safety and tolerability of multiple-dose MLN9708 administration in patients with advanced solid tumors or lymphoma
Inclusion Criteria

Inclusion Criteria

  1. Male or female patients 18 years or older.
  2. Patients must have a histologic or cytologic diagnosis of advanced or metastatic solid tumor or lymphoma for which no standard, curative, or life-prolonging therapies exist or are effective.
  3. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  4. Female patients who:
    • Are postmenopausal for at least 1 year before the screening visit, OR
    • Are surgically sterile, OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 90 days after the last dose of study drug, or
    • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  5. Male patients, even if surgically sterilized (ie, status postvasectomy), who:
    • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, or
    • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  6. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  7. Suitable venous access for the conduct of PK blood sampling for MLN9708.
  8. Clinical laboratory values during the Screening periods as specified below:
    • Absolute neutrophil count (ANC) ≥ 2.5 x 109/L and platelet count > 100 x 109/mL. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days prior to study drug administration.
    • Total bilirubin must be < 1.5 x the upper limit of normal (ULN).
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be < 2.5 x the upper limit of the normal (ULN) range. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of metastatic disease in liver.
    • Calculated creatinine clearance > 30 mL/minute (refer to Section 15.5).
  9. Recovered (ie, ≤ Grade 1 toxicity or patient's baseline status) from the reversible effects of prior anticancer therapy.
Exclusion Criteria

Exclusion Criteria

  1. Female patients who are lactating or breastfeeding or have a positive serum pregnancy test during the Screening period.
  2. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  3. Treatment with any investigational products within 21 days before the first dose of study drug.
  4. Peripheral neuropathy > Grade 2 on clinical examination.
  5. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), moderate inhibitors of CYP1A2 (mexiletine, propafenone, and zileuton), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole), moderate CYP3A inhibitors (amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit-containing products including grapefruit juice, and verapamil), or clinically significant CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, oxcarbazepine, primidone, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before study drug administration in the study.
  6. Patient has symptomatic brain metastasis. Patients with brain metastases:
    • Must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks after completion of the definitive therapy; and
    • Must be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
  7. Ongoing treatment with corticosteroids.
  8. Radiotherapy within 21 days before the first dose of study drug.
  9. Major surgery within 14 days before the first dose of study drug.
  10. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
  11. Life-threatening illness unrelated to cancer.
  12. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection or human immunodeficiency virus (HIV) positive.
  13. Diagnosed or treated for another malignancy within 2 years before the first dose, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  14. Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within the past 6 months.
  15. QTc > 500 milliseconds (msec) on a 12-lead ECG obtained during the Screening period.
  16. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing capsules; diarrhea > Grade 1 despite supportive therapy.
  17. History of urinary or fecal incontinence.
  18. Inability to comply with study procedures or visit schedule including the requirement for inpatient confinement.