a study of nox66 and external beam radiotherapy in patients with metastatic castration-resistant prostate cancer and other solid tumors

Conditions: Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

Summary: this is a phase 1b/phase 2a, open-label, multicenter study to determine the safety, tolerability, recommended phase 2 dose (rp2d), efficacy, pharmacokinetics (pk) and pharmacodynamic (pd) properties of idronoxil when rectally administered as a suppository (nox66) to patients with any solid tumor (part 1) and patients with metastatic castration-resistant prostate cancer (mcrpc), breast cancer (bc) and non-small-cell lung cancer (nsclc) (part 2) who are eligible for low-dose external beam radiotherapy (ebrt) for at least one symptomatic or minimally symptomatic lesion (for the prevention of symptoms).

the study is divided into 2 parts: part 1 (dose escalation) and part 2 (dose expansion). the study design allows an exploration of different doses of nox66 (800 mg, 1200 mg, 1600 mg and 2400 mg) with safety monitoring to ensure the safety of the patients. in cycle 1, nox66 will be administered for 14 days followed by a 7-day rest period on a 21-day cycle. from cycle 2 onwards, nox66 will be administered for 7 days followed by a 7-day rest period on a 14-day cycle. patients will continue to receive nox66 on a cyclical basis until disease progression, unacceptable toxicity, withdrawal of consent, start of a new anticancer therapy, withdrawal of the patient by the investigator or the end of study is reached.

Eligibility criteria:
inclusion criteria: * patient has a minimum life expectancy of 6 months * histological or cytological confirmation of prostate cancer, bc, nsclc and any other solid tumors * confirmed metastatic disease by imaging * documented disease progression following first or later lines of anticancer systemic treatment * patient is eligible for low-dose ebrt for at least one lesion * patients with prior rt are eligible, only if there is no potential for field overlap between the prior rt and the planned rt * for patients with bc or nsclc: patient must have at least one measurable lesion as per recist v1.1 (in part 2 only) * patient has ecog performance status of 0 to 2 * adequate bone marrow, renal, and liver function * metastatic castration-resistant prostate cancer: baseline testosterone levels ≤ 14.4 ng/dl and ongoing medical castration must be maintained throughout the duration of the study; patient has evidence of symptomatic and/or progressive disease * breast cancer patients: known hormone receptor status (estrogen receptors/progesterone receptors or estrogen receptors alone). breast cancer patients are allowed to be on background hormonal treatment. exclusion criteria: * patient has tumor involvement of the central nervous system * impaired cardiac functioning or clinically significant cardiac disease * uncontrolled hypertension despite two concomitant antihypertensive therapies * patients who have had a colectomy (total or left hemicolectomy) with re-anastomosis * patients for whom administration of the suppositories are likely to cause pain or difficulties in absorption * patients with fecal impaction or uncontrolled irritable bowel disease * patients with inflammatory bowel disease * any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent * patients with oligometastatic disease (fewer than 5 metastatic lesions) amenable to standard therapy will be excluded * patients who have had rt to the region of the rectum or will require rt to the region of the rectum during the trial * uncontrolled active infection requiring intravenous antibiotic, antiviral or anti-fungal medications within 14 days before the first dose administration * receiving or having received anticancer treatment * patient has received corticosteroids at a dose of \> 10 mg prednisone/day or equivalent for any reason within 4 weeks prior to receiving the first dose administration * patient is not willing to use suppositories * patient has a positive reverse transcription polymerase chain reaction (rt-pcr) test for severe acute respiratory coronavirus 2 (sars-cov-2) prior to screening or enrollment, or has clinical signs and symptoms consistent with sars-cov-2 infection; e.g., fever, dry cough, dyspnea, sore throat, fatigue or positive sars-cov-2 test result within 2 weeks prior to screening.

Keywords: dose escalation dose expansion prostate-specific antigen maximum tolerated dose recommended phase 2 dose