A Study to Evaluate Rivoceranib Plus Best Supportive Care Compared to Placebo Plus Best Supportive Care in Participants With Gastric Cancer (ANGEL)

Elevar Therapeutics

Status and phase: Completed; Phase 3

Conditions: Gastric Cancer; Gastric Adenocarcinoma

Treatments: Drug: Rivoceranib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03042611

LSK-AM301

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of rivoceranib plus best supportive care (BSC) compared to placebo plus BSC in participants with advanced or metastatic gastric cancer (GC).

Enrollment: 460 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Documented primary diagnosis of histologic- or cytologic-confirmed adenocarcinoma of the stomach or gastroesophageal junction.

2. Locally advanced unresectable or metastatic disease that has progressed since last treatment.

3. One or more measurable or nonmeasurable evaluable lesions per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).

4. Failure or intolerance to at least 2 prior lines of standard chemotherapies with each containing one or more of the following agents:

   • fluoropyrimidine (intravenous [IV] 5-fluorouracil [5-FU] capecitabine, or S-1),
   • platinum (cisplatin or oxaliplatin),
   • taxanes (paclitaxel or docetaxel) or epirubicin,
   • irinotecan,
   • trastuzumab in case of human epidermal growth factor receptor 2 (HER2)-positive,
   • ramucirumab
   • nivolumab
   • pembrolizumab

5. Disease progression within 6 months after the last treatment.

6. Adequate bone-marrow, renal and liver function.

7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.

8. Expected survival of ≥12 weeks, in the opinion of the investigator.

Exclusion criteria

1. History of another malignancy within 2 years prior to randomization except for the following: Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in situ (CIS); Curatively treated cervical CIS; Thyroid papillary cancer with prior treatment; Carcinoma of the skin without melanomatous features; Prostate cancer which had been surgically or medically treated and not likely to recur within 2 years.
2. Central nervous system (CNS) metastases as shown by radiology records or clinical evidence of symptomatic CNS involvement in the last 3 months prior to randomization.
3. Cytotoxic chemotherapy, surgery, immunotherapy, radiotherapy or other targeted therapies within 3 weeks (4 weeks in cases of ramucirumab, mitomycin C, nitrosourea, lomustine; 1 week in case of biopsy) prior to randomization (Adjuvant radiotherapy given to local area for non-curative symptom relief is allowed until 2 weeks before randomization.).
4. Therapy with clinically significant systemic anticoagulant or antithrombotic agents within 7 days prior to randomization that may prevent blood clotting and, in the investigator's opinion, could place the participant at risk.
5. Participants who had therapeutic paracentesis of ascites (>1 Liter [L]) within the 3 months prior to starting study treatment or who, in the opinion of the investigator, will likely need therapeutic paracentesis of ascites (>1L) within 3 months of starting study treatment.
6. Previous treatment with rivoceranib.
7. Known hypersensitivity to rivoceranib or components of the formulation.
8. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9, and CYP2C19.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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460 participants in 2 patient groups

Rivoceranib Plus BSC

Experimental group

Description:

Participants will receive rivoceranib 700 milligrams (mg) orally once per day during each cycle plus BSC. BSC is defined as palliative, non-cancer therapy. Each cycle duration is 28 days.

Treatment:

Drug: Rivoceranib

Placebo

Experimental group

Description:

Participants will receive matching placebo to rivoceranib orally once per day during each cycle plus BSC. BSC is defined as palliative, non-cancer therapy. Each cycle duration is 28 days.

Treatment:

Drug: Placebo