Axelopran for adults with advanced breast, lung, pancreas, or prostate cancer who take opioids

A Phase II Trial of Cancer Response Using Axelopran in Patients With Advanced Cancers on Opioids (AxeCan)

This trial will test whether taking axelopran can slow tumor progression, help bowel problems, and reduce inflammation in adults with advanced breast, lung, pancreas, or prostate cancer who are using opioid pain medicines.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: HealthPartners Institute (Academic / other)
• Drugs / interventions: bevacizumab, chemotherapy, radiation
• Locations: 2 sites (Saint Louis Park, Minnesota and 1 other locations)
• Trial ID: NCT07354919 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase 2 trial giving axelopran as monotherapy to adults with advanced breast, lung (NSCLC), pancreas, or prostate cancer after relapse or progression on standard systemic therapy. The main treatment period for the primary cancer-control assessment is 43 days, and clinicians and patients are asked to delay next-line systemic therapy until that repeat assessment when possible. Key outcomes include signals of slowed tumor progression by RECIST v1.1, safety and tolerability with longer-term use, and effects on bowel function, quality of life, systemic inflammation, cachexia, and serum biomarkers. Eligible participants must be on opioid medication (≥5 mg OME/day) and have at least one measurable lesion.

Who should consider this trial

Good fit: Adults (≥18 years) with advanced or metastatic breast, NSCLC, pancreatic, or prostate cancer who have progressed after standard systemic therapy, are taking opioid medication (average ≥5 mg OME/day), have at least one RECIST-measurable lesion, and are willing to delay next-line systemic therapy until day 43 make ideal candidates.

Not a fit: Patients who are not taking opioids, who have a life expectancy under about two months, who have curative-intent plans, or who cannot delay next-line systemic therapy are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, axelopran could slow tumor growth and improve bowel function, reduce systemic inflammation and cachexia, and potentially delay the need for the next systemic cancer treatment.

How similar studies have performed: Peripheral opioid-receptor antagonists have shown benefit for opioid-related bowel dysfunction, but using axelopran specifically to slow cancer progression and alter inflammation/cachexia is novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

1. Adults (aged 18 or more at enrollment).
2. 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.
3. Advanced stage (locally advanced or metastatic) with no definitive plans for curative-intent therapy.
4. A minimum life expectancy of at least 2 months at the time of the screening visit.
5. Current use of an opioid medication with an average of 5mg OME/day over the past 3 days.
6. At least one measurable lesion meeting RECIST v1.1 criteria.
7. At least 2 weeks since last cancer-directed therapy:

   1. NSCLC and pancreatic cancer must have received at least one line of systemic cytotoxic chemotherapy (+/- immune checkpoint inhibitor) in the locally advanced/metastatic setting.
   2. 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.
   3. 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.
8. 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.
9. 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.
10. Must be willing to report baseline and required patient-reported outcomes and report daily bowel movement frequency for monitoring stool changes.
11. 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).
12. 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.

    1. 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.
    2. Males should refrain from donating sperm during the study and for 90 days after completion of study drug.

Exclusion Criteria:

1. Any previous gastrointestinal surgery, except uncomplicated appendectomy or cholecystectomy.
2. Any of the included cancer cohorts where active malignancy causes direct extension/invasion of the GI tract from local spread or distant metastasis.
3. Current, active, untreated brain metastases.
4. History of fecal incontinence/impaction; irritable bowel syndrome; inflammatory bowel disease; intestinal obstruction; GI or pelvic disorders known to affect bowel transit, produce GI obstruction, or contribute to bowel dysfunction; fecal impaction requiring medical intervention within 1 month of enrollment.
5. Subject is unable to eat, drink, take, or hold down oral medications.
6. Use of buprenorphine, alvimopan, naltrexone, methylnaltrexone, naloxone, lubiprostone, linaclotide, or tapentadol therapy within 14 days before enrollment and inability or unwillingness to discontinue use until the end of the study.
7. Receipt of strong inhibitors of CYP3A4 (e.g., antifungal azoles, grapefruit juice) or strong inducers of CYP3A4 (e.g., rifampin or carbamazepine), including any herbal medications such as St. John's Wort, within the last 14 days or 5 half-lives, whichever is longer, prior to study drug administration.
8. Receipt of inhibitors of p-glycoprotein (P-gp) within the last 14 days prior to study drug administration.
9. Receipt of anti-VEGF therapies (i.e. bevacizumab) within the last 30 days prior to study drug administration.
10. Subjects with clinically significant abnormal ECG at screening or before randomization in the opinion of the Investigator, or a QTc \> 470 msec (per Fridericia's correction).
11. Presence of unstable diseases, in the opinion of the Investigator, such as cardiovascular (e.g., acute myocardial infarction or acute coronary syndrome \< 3 month history), respiratory (e.g., requires oxygen), gastrointestinal (e.g., symptomatic diverticulitis, irritable bowel syndrome \[IBS\], etc.), endocrine (e.g., uncontrolled diabetes or A1c \> 10%), hematologic, neurologic, psychiatric (e.g., schizophrenia, unstable anxiety disorder, acute psychosis, depression with suicidal ideation, etc.), or any other significant conditions that may affect subject assessment.
12. Any other condition which, in the opinion of the investigator, could confound or interfere with evaluation of safety, efficacy, or tolerability of the investigational drug, or prevent compliance with the study protocol.
13. Women who are pregnant, breastfeeding, or of childbearing potential without the use of birth control.

Where this trial is running

Saint Louis Park, Minnesota and 1 other locations

• HealthPartners Frauenshuh Cancer Research Center — Saint Louis Park, Minnesota, United States (Recruiting)
• HealthPartners Cancer Center at Regions Hospital — Saint Paul, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Dylan Zylla, MD, MS — HealthPartners Institute Cancer Research Center
• Study coordinator: Jordan Cowger, MPH

Conditions Breast Cancer; Lung Cancer; Pancreas Cancer; Prostate Cancer; cancer; axelopran; opioids