Abstract
Targeted radiopharmaceuticals for therapeutic use deliver radionuclides directly to tumor anywhere in the body, and therefore, have renewed interest for clinical development in women with disseminated chemorefractory ovarian cancers. About two in every five women with advanced stage ovarian cancer outlive their disease after the first treatment phase, with the rest rendered incurable due to the chemorefractory nature of their disease. The National Cancer Institute (NCI) Cancer Therapy Evaluation Program conducted 67 phase I or phase Ib trials among women with relapsed or refractory ovarian cancer between 1989 and 2017 in an effort to uncover tolerable and effective drug combinations intended to increase survival rates. None of these early clinical development phase trials involved radiopharmaceuticals. Here, the NCI provides its perspective on targeted radiopharmaceutical conjugates alone or in combination with its experimental therapeutics portfolio for women with relapsed or refractory ovarian cancer. An infrastructure build for Federal radiopharmaceutical medical monitoring and adverse event reporting has begun.
Highlights
In 2018, ovarian cancers collectively represent the tenth (2.5%) most common any-type cancer in American women [1]
Pneumonitis or eye corneal/limbic keratitis represent two transient, reversible, or persistent Category B CTCAE subacute toxicity effects attributable in a 3-month window following radiopharmaceutical exposure. These are of particular interest to the National Cancer Institute (NCI) in its clinical development plans
The current NCI position used prior experience from radiopharmaceutical clinical use in ovarian cancer to sharpen its thinking on conjugated radiopharmaceuticals that might be considered for chemorefractory ovarian cancer patient treatment in the near-term
Summary
In 2018, ovarian cancers collectively represent the tenth (2.5%) most common any-type cancer in American women [1]. As NCI leads clinical development of radiopharmaceuticals in the US, it becomes increasingly important to collect and to report radiopharmaceutical-related adverse events in early phase clinical trials for treatment of patients with ovarian cancer or other targeted diseases. NCI has reviewed its prior sponsored experience with radiopharmaceuticals in women with advanced stage ovarian cancer [5,6,7,8], and considers the toxicity profile of such experimental therapeutic radiopharmaceuticals of acceptable risk for early phase clinical trial study. Pneumonitis or eye corneal/limbic keratitis represent two transient, reversible, or persistent Category B CTCAE subacute toxicity effects attributable in a 3-month window following radiopharmaceutical exposure These are of particular interest to the NCI in its clinical development plans. Employed during the study, how the plan addresses important risks and ensures validity of timing, frequency, logs, and extent of planned monitoring activities as well as definitions of events triggering changes or deviations in planned monitoring activities; (B) communication of monitoring results inclusive of format, content, timing, and archiving requirements for reports and other documentation of monitoring activities from study management and other stakeholders (like site staff, IRB, NCI, FDA), as necessary; (C) processes for addressing unresolved or significant non-compliance with the investigational plan, inclusive of root cause analyses and appropriate corrective and preventive actions for quality management practices applicable to a clinical investigation; (D) description of specific training required for personnel carrying out monitoring activities, including personnel conducting internal data monitoring, statistical monitoring, or other centralized review activities or planned audits of monitoring; and (E) accounting of monitoring plan amendments
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