A Phase I/Randomized Phase II Study of Cediranib (NSC#732208) Versus Placebo in Combination With Cisplatin and Pemetrexed in Chemonaive Patients With Malignant Pleural Mesothelioma

This randomized phase I/II trial is studying the side effects and best dose of cediranib maleate when given together with pemetrexed disodium and cisplatin and to see how well it works in treating patients with malignant pleural mesothelioma. Drugs used in chemotherapy, pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving pemetrexed disodium and cisplatin together with cediranib maleate may kill more tumor cells.
Cancer (Oncology) - Lung, Cancer (Oncology)
Gary Goodman, M.D.
Swedish Cancer Institute
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed malignant pleural mesothelioma

    • Not planning to undergo surgical resection
  • Patients must have measurable or non-measurable disease by both RECIST and modified RECIST criteria for pleural tumors as documented by CT scan; examinations for assessment of measurable disease must have been completed within 28 days prior to registration; examinations for assessment of non-measurable disease must have been performed within 42 days prior to registration; all disease must be assessed and documented on the RECIST 1.1 and Modified RECIST Baseline Tumor Assessment Form
  • Zubrod performance status 0-2
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL (transfusion allowed)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT or SGPT ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases are present)
  • Serum creatinine ≤ 1.5 times ULN
  • Creatinine clearance ≥ 60 mL/min
  • Proteinuria ≤ +1 on 2 consecutive dipsticks taken ≥ 7 days apart

    • Repeat urinalysis not required provided first urinalysis shows no protein
  • Not pregnant or nursing
  • Fertile patients must agree to use effective contraception
  • Must be able to swallow oral medications
  • No mean QTc > 500 msec (with Bazett correction) by ECG or other significant ECG abnormality
  • No NYHA class III-IV congestive heart failure
  • No clinically significant hemoptysis, defined as > 1 tablespoon of bright red blood, within the past year
  • No known HIV infection
  • No other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I or II cancer from which the patient is currently in complete remission.
  • No other concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer
  • No prior systemic therapy (chemotherapy or other biological therapy) for unresectable malignant pleural mesothelioma

    • Prior systemicchemotherapy or biologic therapy as neoadjuvant or adjuvant therapy allowed provided disease has recurred and systemic therapy was completed > 6 months before study entry
  • No prior therapy with any of the study drugs
  • At least 28 days since prior surgery (e.g., pleurectomy, pleurodeses, thoracic or other major surgeries) and recovered
  • At least 28 days since prior radiotherapy and recovered
  • No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
  • No concurrent drugs or biologics with proarrhythmic potential
  • No concurrent major surgery
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