A Phase II Trial of Cancer Response Using Axelopran in Patients With Advanced Cancers on Opioids (AxeCan)
The primary objective of this single arm, open label, phase II trial is to determine if axelopran use impacts cancer control in patients with advanced cancers of the lung, breast, pancreas, and prostate. The primary study period for assessing the primary aim is through day 43 (6 weeks). The main questions it aims to answer are: * Does axelopran show a signal for efficacy in slowing tumor progression? * Is axelopran safe and tolerable for long-term use in this patient population? * Does axelopran show a signal for efficacy in improving bowel function and quality of life? * Does axelopran show a signal for efficacy in reducing systemic inflammation, cachexia, and prognostic serum biomarkers of inflammation? Patients will take axelopran as monotherapy after relapse or progression on or after standard systemic therapy. Clinician and patient must be willing to attempt a delay in next line of systemic cancer therapy (if available) until day 43 to assess change in cancer status on repeat imaging. Clinician can move to the next line of therapy whenever deemed clinically necessary. Participants will: * take oral axelopran capsules daily for up to 1 year, or longer if deriving benefit * attend 10 in-person study visits, each lasting approximately 1-2 hours * complete study procedures including but not limited to imaging exams, blood draws, electronic health surveys, and physical assessments
• Adults (aged 18 or more at enrollment).
• Histologically or cytologically proven cancer of the prostate (carcinoma), breast (carcinoma), pancreas (carcinoma), and lung (non-small cell lung carcinoma (NSCLC)) that has relapsed or progressed on or after a standard systemic treatment that has included cytotoxic chemotherapy.
• Advanced stage (locally advanced or metastatic) with no definitive plans for curative-intent therapy.
• A minimum life expectancy of at least 2 months at the time of the screening visit.
• Current use of an opioid medication with an average of 5mg OME/day over the past 3 days.
• At least one measurable lesion meeting RECIST v1.1 criteria.
• At least 2 weeks since last cancer-directed therapy:
∙ NSCLC and pancreatic cancer must have received at least one line of systemic cytotoxic chemotherapy (+/- immune checkpoint inhibitor) in the locally advanced/metastatic setting.
‣ Breast cancer must be considered refractory to hormone therapy (i.e., progressed on standard estrogen blocking therapy) or hormone negative (i.e., estrogen and progesterone-receptor negative) and have received at least one line of systemic cytotoxic chemotherapy in the locally advanced/metastatic setting.
‣ Prostate cancer must be considered metastatic castrate-resistant prostate cancer (mCRPC) and have progressed on at least one androgen receptor pathway inhibitor (ARPI) and docetaxel. Docetaxel could be given in the metastatic castrate-sensitive setting, and/or later in the mCRPC setting. Baseline testosterone level must be \<50 ng/dL and surgical or ongoing medical castration must be maintained throughout the duration of the study.
• Patients must a) have relapsed or progressed on or after all standard therapy, b) be intolerant to standard therapy, c) not have standard therapy available that confers a significant clinical benefit, d) decline other standard therapy or agree with treating oncologist that a period of active surveillance off therapy is reasonable.
• Clinician and patient are willing to attempt a delay in next line of systemic cancer therapy (if available) until day 43 to assess change in cancer status on repeat imaging. Clinician can move to next line of therapy at any time if a patient's clinical course changes and urgent new treatment is required. Patients will be allowed to remain on axelopran if that occurs.
• a) Planned palliative radiation therapy should be completed prior to study enrollment. Palliative radiation done during the primary study period would be considered next line of cancer therapy.
⁃ Must be willing to report baseline and required patient-reported outcomes and report daily bowel movement frequency for monitoring stool changes.
⁃ For a female subject of childbearing potential, must have documentation of a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1. All women are considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 2 years) or documented to be surgically sterile (bilateral tubal ligation or hysterectomy).
⁃ Sexually active subjects must use a highly effective method of contraception during the study and for at least 90 days after completion of study drug dosing.
• A highly effective method of birth control is defined as one that results in a low failure rate (i.e., \< 1% per year) when used consistently and correctly, such as condom + diaphragm, condom + spermicide, diaphragm + spermicide, or intrauterine device (IUD) with documented failure rate of \< 1% per year, or oral/injectable/implanted hormonal contraceptives used in combination with an additional barrier method.
∙ Males should refrain from donating sperm during the study and for 90 days after completion of study drug.