Oral Paclitaxel Plus Fruquintinib Verus Investigator's Choice in Second-Line Advanced Gastric Cancer (FREEDOM)

Paclitaxel Oral Solution Plus Fruquintinib Versus Investigator's Choice as Second-Line Treatment for Advanced Gastric Cancer: A Multicenter, Open-Label, Randomized Controlled Trial

The goal of this study is to evaluate the efficacy and safety of oral paclitaxel solution plus fruquintinib as second-line therapy in adult subjects with advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer or Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Oral Paclitaxel Solution Plus Fruquintinib; Drug: Investigator Choice (IC) Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yanqiao Zhang; Phone Number: 86-138 4512 0210; Email: yanqiaozhang@ems.hrbmu.edu.cn

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • The Affiliated Hospital of Harbin Medical University
      • Contact: Dan Su
      • Contact: Yanqiao Zhang; Phone Number: 86-138 4512 0210; Email: yanqiaozhang@ems.hrbmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 to 75 years, regardless of sex;
2. Histologically and/or cytologically confirmed advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma that has failed first-line therapy or developed intolerable toxicity to first-line treatment.
3. Presence of at least one measurable lesion per RECIST v1.1 criteria (Note: Previously irradiated lesions cannot be used as target lesions unless unequivocal progression of the lesion after radiotherapy is documented);
4. Body weight ≥40 kg or BMI >18.5 kg/m²;

5. No severe hematologic, hepatic, or renal abnormalities:

   1. Hematology: Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Platelet count (PLT) ≥100×10⁹/L; Hemoglobin (Hb) ≥90 g/L;
   2. Chemistry: Total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN); ALT and AST ≤2.5×ULN in the absence of liver metastases, or ≤5×ULN if liver metastases are present; Serum creatinine (Cr) ≤1.5×ULN;
   3. Urinalysis: Urine protein ≤1+; If urine protein is ≥2+, a 24-hour urine protein test must be performed, and enrollment is permitted only if the 24-hour urine protein is <1.0 g;
6. ECOG Performance Status (PS) 0-1;
7. Life expectancy ≥12 weeks;
8. Signed informed consent.

Exclusion Criteria:

1. Known HER2-positive status without prior anti-HER2 therapy (patients who progressed after anti-HER2 therapy are eligible);
2. History of another primary malignancy within 3 years prior to the first study drug administration, except for adequately treated basal cell or squamous cell carcinoma of the skin, or in situ carcinomas of the cervix, breast, or other sites;
3. Receipt of radiotherapy (except palliative radiotherapy), chemotherapy, or small-molecule targeted anticancer therapy within 4 weeks or within 5 half-lives of the agent (whichever is shorter) prior to the first dose of study drug. Patients who discontinued other investigational agents for more than 5 half-lives are eligible for screening. Additionally, treatment with large-molecule targeted anticancer agents within 4 weeks prior to the first study drug dose is prohibited;
4. Toxicity from prior anticancer therapy not recovered to ≤ Grade 1 or baseline levels (except alopecia; neurotoxicity must have resolved to ≤ Grade 2) within 2 weeks prior to the first study drug administration;
5. Presence of dysphagia, uncontrolled nausea, vomiting, diarrhea, or known malabsorption syndrome that may interfere with oral drug absorption;
6. Active gastrointestinal conditions such as gastric/duodenal ulcer, ulcerative colitis, or bowel obstruction, or any other condition deemed by the investigator to carry a risk of gastrointestinal hemorrhage or perforation; history of gastrointestinal perforation or fistula within the past 6 months; or incomplete recovery from surgery related to gastrointestinal perforation or fistula;
7. Evidence of significant bleeding or history of bleeding (e.g., hematemesis, hemoptysis) within 2 months prior to randomization. Patients with melena and positive fecal occult blood test must undergo gastroenteroscopy to rule out active bleeding or active ulcer before enrollment;
8. Requirement for long-term use of proton pump inhibitors (PPIs) or H2-receptor antagonists during the trial; or use of strong inducers or inhibitors of cytochrome P450 (CYP) 3A4 or CYP2C8 within 2 weeks prior to the first study drug dose;
9. Known active central nervous system (CNS) metastases and/or leptomeningeal carcinomatosis;
10. Active infections or serious infectious diseases, including but not limited to: HIV infection (positive HIV antibody), active hepatitis (active HCV infection defined as positive HCV RNA; HCV antibody-positive but RNA-negative patients are allowed), active HBV infection (HBsAg-positive with HBV DNA >2000 IU/mL), bacteremia, severe pneumonia requiring systemic therapy, or active tuberculosis;
11. Any of the following cardiovascular conditions: myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Class ≥2), or other clinically significant cardiac disease within 6 months prior to the first study drug dose; clinically significant ECG abnormalities (e.g., arrhythmias, QTc interval >450 ms); left ventricular ejection fraction (LVEF) <50% on echocardiography; or uncontrolled hypertension despite treatment with ≥2 antihypertensive agents (systolic BP >140 mmHg or diastolic BP >90 mmHg);
12. Prior systemic therapy targeting VEGF or VEGFR; or prior treatment with paclitaxel, docetaxel, nab-paclitaxel, liposomal paclitaxel, or polymeric micelle paclitaxel;
13. Known hypersensitivity to any component of the investigational product;
14. Pregnant or lactating women;
15. Uncontrolled symptomatic pleural, peritoneal, or pericardial effusion requiring repeated drainage. Asymptomatic patients with minimal effusions detected only on imaging and who have not received drainage or other intervention within 2 weeks prior to enrollment are eligible;
16. Major surgery (e.g., craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to first dosing, or presence of non-healed surgical wounds, ulcers, or fractures. Patients may be enrolled if the investigator determines they are fit to receive study drug ≥2 weeks post-surgery;
17. History of deep vein thrombosis, pulmonary embolism, or other significant thromboembolic events within 3 months prior to study entry; ongoing anticoagulation therapy with warfarin, low-molecular-weight heparin, or similar agents. Prophylactic low-dose anticoagulation is permitted if INR ≤1.5 per inclusion criteria;
18. Chronic use of nonsteroidal anti-inflammatory drugs (e.g., indomethacin, ibuprofen) or antiplatelet agents (e.g., clopidogrel, ticlopidine, dipyridamole). Low-dose aspirin (≤325 mg/day) is allowed;
19. Any other condition deemed by the investigator as unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Paclitaxel Solution Plus Fruquintinib; Oral paclitaxel solution: 200mg/m2, p.o., bid, on days 1, 8, and 15 of each 28-day cycle. Fruquintinib: 4 mg orally once daily, 3 weeks on/1week off	Drug: Oral Paclitaxel Solution Plus Fruquintinib; Patients received oral paclitaxel plus fruquintinib in 4-week cycles until disease progression, death, unacceptable toxicity, withdrawal of consent, iscontinuation by the investigator or study completion or termination.
Active Comparator: Investigator-Selected Chemotherapy; Investigator-selected chemotherapy includes injectable taxanes (paclitaxel injection, albumin-bound paclitaxel, docetaxel, etc.), irinotecan, etc., excluding oral paclitaxel solution. Regimens and doses shall be determined by the investigator in accordance with recommendations from current clinical guidelines.	Drug: Investigator Choice (IC) Chemotherapy; Investigator' choice of chemotherapy is given until disease progression, death, unacceptable toxicity, withdrawal of consent, iscontinuation by the investigator or study completion or termination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival（PFS）	Progression-free survival (PFS) is defined as the time from the date of randomization to disease progression per RECIST 1.1 or death due to any cause, whichever occurs first.	assessed up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate（ORR）	ORR is defined as the percentage of subjects who have a Complete Response (CR) or Partial Response (PR) per RECIST 1.1	assessed up to 1 year
Disease Control Rate（DCR）	DCR is defined as the proportion of subjects whose BOR is rated as CR, PR, or stable disease (SD) per RECIST 1.1	assessed up to 1 year
Overall survival（OS）	OS is defined as the time from the date of randomization to the date of death, regardless of the cause of death.	From randomization until death due to any cause, up to 3 years.
Adverse event	Use NCI-CTCAE version 5.0 for classification and grading.	From first dose to 30 days post the last dose
Qualtiy of life assesd by EORTC QLQ-C30 v3.0	EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures global health status. There are 30 items in total, which can be divided into 15 fields. Five functional scales: physical function, role function, cognitive function, emotional function, social function; Three symptom scales: fatigue, pain, nausea and vomiting; Six individual measures: dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties, and a global quality of life scale. The five functional scales and the global quality of life scale were scored independently. After linear transformation, the scores of all items ranged from 1 to 100, and the higher score, the higher functional level. The symptom scale was also scored independently and linearly transformed into a score from 1 to 100, with higher scores indicating more serious problems or symptoms.	Evaluation from baseline to the 30 days post the last dose

Collaborators and Investigators

• Sponsor: Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 27, 2026

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Therapeutics; Drug Therapy; HMPL-013
• Other Study ID Numbers: OT-2005-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No