Clinical trial NCT05265052: 3D1002 in Combination With Oxycodone Hydrochloride Sustained-release Tablets in Patients With Moderate to Severe Cancer Pain
Official title: A Multicenter, Randomized, Phase IIa/IIb Clinical Trial of 3D1002 Combined With Oxycodone Hydrochloride Sustained-release Tablets in the Treatment of Patients With Moderate to Severe Cancer Pain
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Cancer Pain
Keywords: Cancer pain
Lead sponsor: 3D Medicines
Sponsor class: INDUSTRY
First posted: 2022-03-03
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Both phase IIa and IIb are randomized, parallel controlled studies.
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the safety and efficacy of 3D1002 alone or in combination with oxycodone hydrochloride sustained-release tablets (OxyContin) for the management of moderate or severe cancer pain.

Detailed description: The investigational product in this study, 3D1002, is a selective antagonist of prostaglandin E2 receptor subtype 4 (EP4). The study is composed of two stages. Phase IIa stage is to assess the safety and efficacy of 3D1002 administered at doses of 50, 100 or 150 mg every 12 hour (q12h) for patients with moderate to severe cancer pain, and to determine the optimal recommended dose for further studies. Phase IIb stage is to evaluate the difference in the efficacy and safety of 3D1002 combined with OxyContin and OxyContin alone in treatment of patients with moderate to severe cancer pain.

Eligibility criteria: Inclusion Criteria:

1. Subject must sign the informed consent in person prior to beginning any screening procedure.
2. Age ≥18, both male and female.
3. Subjects with a malignant tumor confirmed by histopathology or cytology.
4. Weight ≥40 kg at screening period.
5. Subjects have relatively stable cancer pain and require continuous analgesic medications (estimated treatment duration ≥2 weeks), as assessed by the investigator.
6. Estimated life expectancy ≥3 months.
7. Subjects are willing to not use any analgesic other than those specified in the study during the study treatment period.
8. ECOG PS score is 0-3.
9. Have adequate organ and bone marrow function.
10. The mean NRS scores per day during the washout period are ≥4.

Exclusion Criteria:

1. Known allergy to any of the active ingredients or excipients of the study drug, or have a history of allergy to other opioids or non-steroidal anti-inflammatory drugs (NSAIDs) and their related ingredients.
2. Have a persistent pain resulted from other medical conditions or unknown causes.
3. Subjects presenting with emergency symptoms such as intestinal obstruction/perforation, spinal cord compression, epidural metastasis, or fracture.
4. Subjects with known active/symptomatic central nervous system metastasis and/or cancerous meningitis.
5. Subjects plan to be treated with \>10 mg/ day of prednisone or equivalent systemic corticosteroid during the study period.
6. Have a history of gastrointestinal bleeding or perforation.
7. Have a positive result of fecal occult blood test during screening period.
8. Have a history of serious cardiovascular diseases.
9. Have a history of an acute ischemic or hemorrhagic stroke within 6 months prior to screening.
10. Have a history of significant psychiatric disorders, such as schizophrenia and depression.
11. Subjects plan to receive radiotherapy, surgery, or a new regimen of systemic antitumor agents during the study treatment period (D1-D15).
12. Subjects have a history of alcohol abuse or drug abuse including opioids.
13. Subjects have significant opioid contraindications.
14. Pregnant or lactating women.
15. Subjects with other diseases that affect the oral administration or absorption of drugs.
16. Subjects are currently participating in another clinical study.
17. Other conditions deemed by the investigator to be inappropriate for participation in this study, such as poor compliance.

Primary outcomes:
measure: Sum of pain intensity difference in the Numeric Rating Scale (NRS) within 14 days after the first study drug treatment (SPID14)
timeFrame: 1 to 14 days after receiving study treatment
Secondary outcomes:
measure: Proportion of subjects who achieve effective pain control
timeFrame: 1 to 14 days after receiving study treatment
measure: Time to achieve effective pain control
timeFrame: 1 to 14 days after receiving study treatment
measure: Time-specific pain intensity difference（PID）
timeFrame: 1 to 14 days after receiving study treatment
measure: Sum of pain intensity difference (SPID) in the NRS within 3,5 and 7 days post-treatment
timeFrame: from day 1 to 3, 5 and 7 after receiving study treatment, respectively
measure: Time-specific subject self-rated pain relief based on Brief Pain Inventory Short Form (BPI-SF) Questionnaire Item 8
timeFrame: 1 to 14 days after receiving study treatment
measure: Sum of subject self-rated pain relief based on BPI-SF Questionnaire Item 8 within 3,5,7 and 14 days post-treatment
timeFrame: from day 1 to 3, 5, 7 and 14 after receiving study treatment, respectively
measure: Proportion of subjects with pain response over 7 and 14 days after treatment
timeFrame: 1 to 14 days after receiving study treatment
measure: Time to pain response
timeFrame: 1 to 14 days after receiving study treatment
measure: The number of breakthrough pain episodes and rescue dose of immediate-release oxycodone over 7 and 14 days after treatment;
timeFrame: 1 to 14 days after receiving study treatment
measure: Time-specific oxycodone dose, including immediate-release oxycodone capsules and sustained-release oxycodone tablets (the latter is only applicable for phaseⅡb)
timeFrame: 1 to 14 days after receiving study treatment
measure: Total dose of oxycodone over 3, 7, and 14 days post-treatment
timeFrame: 1 to 14 days after receiving study treatment
measure: Evaluation of the subjects' quality of life over 7 and 14 days after treatment by using of European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 V3.0) (for phase Ⅱb only)
timeFrame: 1 to 14 days after receiving study treatment
measure: Patient's global impression of change (PGI-C) over 7 and 14 days after treatment (for phase IIb only)
timeFrame: 1 to 14 days after receiving study treatment
measure: Frequency and severity of adverse events during treatment
timeFrame: 1 to 14 days after receiving study treatment
Other outcomes:
Locations:
Study officials:
affiliation: Henan Cancer Hospital
name: Suxia Luo
role: PRINCIPAL_INVESTIGATOR
References: