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Clinical Trial 19953

Cancer Type: Thoracic
Interventions:Celecoxib (); Gemzar (gemcitabine); gemcitabine (); rAd-IFN ()

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Tawee Tanvetyanon

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase 3, Open-Label, Randomized, Parallel Group Study to Evaluate the Efficacy and Safety of Intrapleural Administration of Adenovirus-Delivered Interferon Alpha-2b (rAd-IFN) in Combination with Celecoxib and Gemcitabine in Patients with Malignant Pleural Mesothelioma

Summary

The primary objective of this study is to compare the overall survival (OS) associated with rAd-IFN, when administered with celecoxib and gemcitabine, versus that associated with celecoxib and gemcitabine alone for the treatment of patients with MPM who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen.

Objective

The primary objective of this study is to compare the overall survival (OS) associated with rAd-IFN, when administered with celecoxib and gemcitabine, versus that associated with celecoxib and gemcitabine alone for the treatment of patients with MPM who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen. The secondary objectives are To compare between rAd-IFN, when administered with celecoxib and gemcitabine, versus that associated with celecoxib and gemcitabine alone for the treatment of patients with MPM who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen, with respect to: Survival rate at 12 months and every 6 months thereafter; Progression-free survival (PFS); Best response (complete response, partial response, or stable disease); and Safety of rAd-IFN; and To evaluate rAd-IFN, when administered with celecoxib and gemcitabine, in a sub-set of patients with MPM who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen, with respect to viral shedding and biodistribution. The exploratory objectives of this study are: To compare between rAd-IFN, when administered with celecoxib and gemcitabine, versus that associated with celecoxib and gemcitabine alone for the treatment of patients with MPM who have failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, 1 of which must have been an anti-folate and platinum combination regimen, with respect to: Health-related Quality-of-Life, The relationship between immunological status and response to treatment, and Biocorrelates of response to treatment.

Inclusion Criteria

  • Has a confirmed histological diagnosis of MPM with histological type epithelioid or biphasic (if biphasic, histology must be predominantly [>50%] epithelioid). Histological diagnosis of MPM will be confirmed centrally using specimens or slides from tumor specimens obtained at the time of initial presentation or a subsequent procedure. Central confirmation of diagnosis with immunohistochemistry will be performed, and independent central confirmation will be required for study entry;
  • Measurable disease, per modified Response Evaluation Criteria in Solid Tumor [RECIST] for pleural mesothelioma;
  • Has failed a minimum of 1 treatment regimen and a maximum of 2 treatment regimens, which may have been chemotherapeutic and/or immunotherapeutic treatment regimens for MPM which included at least 1 anti-folate and platinum combination regimen. Adjuvant or neoadjuvant therapy represent 1 line of therapy each. Participants who have undergone primary surgical resection and/or radiation therapy to the pulmonary site are eligible to participate. For clarity, surgical resection and/or radiation therapy to the pulmonary site are not exclusionary and are not considered a line of therapy;
  • Has a pleural space accessible for IPC or similar device. Participants with a previously inserted IPC or similar device may be enrolled, and the pre-existing IPC or similar device can be used for vector administration as long as it is functional and has no evidence of local infection;
  • Life expectancy >12 weeks in the judgement of the Investigator;
  • Eastern Cooperative Oncology Group (ECOG) status of 1 or 0;
  • Female and male participants:
  • Female participants of childbearing potential must have a negative pregnancy test upon entry into this study and agree to use a highly effective method of contraception from Screening until 1 month after the last dose of gemcitabine;
  • Highly effective methods of contraception that result in a low failure rate (i.e., >True abstinence, when in line with the preferred and usual lifestyle of the participant, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of study participation and for 1 month after the last dose of gemcitabine. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, and post-ovulation method) and withdrawal are not acceptable methods of contraception; and
  • Female participants of non-childbearing potential must be either postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile upon entry into the study;
  • Male participants must be either surgically sterile or agree to use a double-barrier contraception method from Screening until 6 months after the last dose of gemcitabine. Where available and in accordance with local practices, male patients must be advised to seek further advice regarding cryoconservation of sperm prior to gemcitabine treatment due to the possibility of infertility after therapy with gemcitabine; and
  • Adequate laboratory values at Screening per protocol

  • Exclusion Criteria

  • Is "treatment-naïve" (i.e., has not received at least 1 anti-folate and platinum combination regimen);
  • Has previously received 3 or more lines of systemic chemotherapeutic or immunotherapeutic treatment;
  • Has previously received treatment with gemcitabine;
  • Has stage IV extrathoracic metastatic disease;
  • Inadequate pulmonary function of clinical significance as per Investigator review;
  • Clinically significant pericardial effusion (i.e., as judged by the Investigator and/or requiring drainage) detected by computed tomography (CT) scan at Screening;
  • Prior therapy(ies), if applicable, must be completed according to the criteria below prior to vector administration:
  • Cytotoxic chemotherapy, at least 21 days from last dose;
  • Non-cytotoxic chemotherapy (e.g., small molecule inhibitor), at least 14 days from last dose;
  • Monoclonal antibody, at least 30 days from last dose;
  • Non-antibody immunotherapy (e.g., tumor vaccine), at least 42 days from last dose;
  • Radiotherapy, at least 14 days from last local site radiotherapy;
  • Hematopoietic growth factor, at least 14 days from last dose; or
  • Study drug, 30 days or 5 half-lives, whichever is longer, from last dose;
  • Participant previously treated with IFNs (e.g., for chronic active hepatitis);
  • Suspected/known hypersensitivity to IFN-α2b;or rAd-IFN (including any of its excipients);
  • Known hypersensitivity to celecoxib (including any of its excipients) or sulfonamides;
  • Known hypersensitivity to gemcitabine (including any of its excipients);
  • Impaired cardiac function or clinically significant cardiac disease including the following:
  • New York Heart Association class III or IV congestive heart failure;
  • Myocardial infarction within the last 12 months; and
  • Participants known to have impaired left ventricular ejection fraction per institutional standards and of clinical significance as per Investigator review;
  • Women who are pregnant or breastfeeding;
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, depression, or psychiatric illness/social situations within the last 12 months;
  • Participants with active, known, or suspected auto-immune disease or a syndrome that requires systemic or immunosuppressive agents (oral prednisolone or equivalent at a dose of >History of asthma, acute rhinitis, nasal polyps, angioneurotic edema urticaria, or other allergic-type reactions after taking acetylsalicylic acid or NSAIDs including COX-2 inhibitors;
  • History of ulcer disease or gastrointestinal bleeding;
  • Uncontrolled or poorly controlled hypertension (i.e; blood presure >160/100 mmHg) requiring 3 or more anti-hypertensive drugs;
  • Heart rate corrected QT interval using Fridericia's fomula >470 ms on resting 12-lead electrocardiogram (ECG);
  • Participants receiving lithium;
  • Any significant disease which, in the opinion of the Investigator, would place the participant at increased risk of harm if he/she participated in the study;
  • History of prior malignancy for which treatment was complet4ed >Has a congenital or acquired immunodeficiency, including participants with known history of infection with human immunodeficiency virus.
  • Other exclusions apply