A Study of AL2846 Capsule Combined With Standard Chemotherapy Regimen in Subjects With Advanced Colorectal Cancer

CTTQ

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Advanced Colorectal Cancer

Treatments: Drug: 5-FU; Drug: Oxaliplatin; Drug: AL2846; Drug: Irinotecan; Drug: Calcium folate

Study type: Interventional

Funder types: Industry

Identifiers

NCT04337879

AL2846-I-0004

Details and patient eligibility

About

This is a study to explore the safety, tolerance and efficacy of AL2846 capsules combined with mFOLFOLX6 or FOLFIRI standard chemotherapy regimen in subjects with advanced metastatic colorectal cancer.

Enrollment: 56 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

-1. Histologically confirmed advanced metastatic colorectal cancer. 2. Has received only first-line standard chemotherapy regimen for metastatic disease, and which was failed.

3. At least one measurable lesion. 4. Has received systemic chemotherapy, palliative radiotherapy or other anti-tumor therapy before first dose at least 4 weeks.

5.18 and 75 years old; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months.

6. Adequate laboratory indicators. 7. No pregnant or breastfeeding women, and a negative pregnancy test. 8. Understood and signed an informed consent form.

Exclusion criteria

• 1. Diagnosed and/or treated additional malignancy within 5 years with the exception of basal cell carcinoma of the skin and carcinoma in situ of the cervix.

  2. Has received radiotherapy, chemotherapy and surgery before and less than 4 weeks from the first administration and less than 5 half-lives of oral targeted drugs after the completion of treatment.

  3. Has multiple factors that affect oral medications. 4. Has gastroduodenal ulcer, ulcerative colitis, intestinal obstruction and other gastrointestinal diseases or other conditions judged by the investigator that may cause gastrointestinal bleeding or perforation.

  4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.

  5. Has arterial or deep vein thrombosis events in 6 months. 7. Hypersensitivity to AL2846 or its excipient. 8. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear.

  6. Has symptomatic brain metastases, spinal cord compression, and cancerous meningitis within 8 weeks,or brain or pia mater disease confirmed by CT or MRI examination before the first dose.

  10.Has adverse events caused by previous therapy that did not recover to ≤ grade 1, with the exception of alopecia or ≥ grade 2 neurotoxicity caused by Oxaliplatin.

  11. Subjects plan to receive FOLFIRI chemotherapy regimen with uridine diphosphate glucuronyltransferase homozygous variant or double hybrid variant.

  12. Has drug abuse history that unable to abstain from or mental disorders. 13. Has any serious and/or uncontrolled disease. 14. Has received allogeneic organ transplants, hematopoietic stem cell transplants or bone marrow transplants.

  13. Has participated in other clinical trials within 4 weeks before the first dose.

  14. According to the investigators' judgment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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56 participants in 2 patient groups

AL2846 + mFOLFOX6

Experimental group

Description:

AL2846 capsule administered orally,once daily in 28-day cycle; oxaliplatin 85mg/ ㎡ administered intravenously (IV) on day 1, day 15 in 28-day cycle；calcium folate 400mg/ ㎡ IV on day 1, day 15 in 28-day cycle；5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 in 28-day cycle.

Treatment:

Drug: Oxaliplatin

Drug: AL2846

Drug: Calcium folate

Drug: 5-FU

AL2846 + FOLFIRI

Experimental group

Description:

AL2846 capsule administered orally,once daily in 28-day cycle; irinotecan 180mg/㎡ administered intravenously (IV) on day 1,15 in 28-day cycle; calcium folate 400mg/ ㎡ IV on day 1,15 in 28-day cycle; 5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 days in 28-day cycle.

Treatment:

Drug: AL2846

Drug: Calcium folate

Drug: Irinotecan

Drug: 5-FU