Ramucirumab + Trifluridine/Tipiracil or Paclitaxel for Gastric Cancer
Recruiting in Palo Alto (17 mi)
+7 other locations
Overseen byMohamad B Sonbol
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Academic and Community Cancer Research United
Must not be taking: Antiplatelets, Antiretrovirals
Disqualifiers: Pregnancy, Severe disease, Recent surgery, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II trial studies the effect of the combination of ramucirumab and trifluridine/tipiracil or paclitaxel in treating patients with previously treated gastric or gastroesophageal junction cancer that has spread to other places in the body (advanced). Ramucirumab may damage tumor cells by targeting new blood vessel formation. Trifluridine/tipiracil is a chemotherapy pill and that may damage tumor cells by damaging their deoxyribonucleic acid (DNA). Paclitaxel may block cell growth by stopping cell division which may kill tumor cells. Giving ramucirumab and trifluridine/tipiracil will not be worse than ramucirumab and paclitaxel in treating gastric or gastroesophageal junction cancer.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but if you are on warfarin, you must switch to low molecular weight heparin before starting the trial. Also, if you are on full-dose anticoagulation, you need to be on a stable dose for at least 14 days before starting the trial.
What data supports the effectiveness of the drug combination of Ramucirumab and Trifluridine/Tipiracil for gastric cancer?
Trifluridine/Tipiracil has been shown to improve overall survival and disease control in patients with metastatic gastric cancer, as demonstrated in the TAGS trial. Additionally, Ramucirumab, alone or with Paclitaxel, has been effective as a second-line therapy for advanced gastric cancer, according to the REGARD and RAINBOW trials.
12345Is the combination of Ramucirumab and Trifluridine/Tipiracil safe for treating gastric cancer?
The combination of Ramucirumab and Trifluridine/Tipiracil for advanced gastric cancer has shown an acceptable safety profile in clinical trials. Common side effects include blood-related issues like neutropenia (low white blood cell count) and gastrointestinal problems such as nausea and diarrhea, which are generally manageable with dosage adjustments and supportive care.
14567What makes the drug combination of Ramucirumab, Trifluridine/Tipiracil, and Paclitaxel unique for treating gastric cancer?
This drug combination is unique because it combines Ramucirumab, which targets blood vessel growth in tumors, with Trifluridine/Tipiracil, a chemotherapy that disrupts cancer cell DNA, and Paclitaxel, another chemotherapy that prevents cancer cells from dividing. This multi-faceted approach aims to enhance effectiveness against advanced gastric cancer compared to using these drugs individually.
35689Eligibility Criteria
Adults with advanced gastric or gastroesophageal junction cancer that has worsened within 6 months after treatment can join. They must have had prior chemotherapy, be in good physical condition, and able to take oral meds. Pregnant women, nursing mothers, those with recent serious health issues like heart attacks or uncontrolled hypertension are excluded.Inclusion Criteria
Hemoglobin >= 9.0 g/dL (obtained =< 7 days prior to registration)
Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3 x ULN ( =< 5.0 x UNL, if with liver metastasis) (obtained =< 7 days prior to registration)
My advanced cancer has worsened within 6 months after my last treatment.
+24 more
Exclusion Criteria
I understand the study drug's effects on unborn babies are unknown.
I have been treated with TAS-102 or ramucirumab before.
I received taxane therapy less than 6 months ago.
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive either TAS-102 and ramucirumab or paclitaxel and ramucirumab. Treatment repeats every 28 days for up to 36 cycles.
Up to 36 cycles (approximately 3 years)
Visits on days 1, 8, and 15 of each 28-day cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment completion
3 years
Follow-up at 30-35 days post-treatment, then every 3 months
Participant Groups
The trial is testing the effectiveness of ramucirumab combined with either trifluridine/tipiracil or paclitaxel in patients who've already been treated for advanced stomach cancers. Ramucirumab targets blood vessel growth in tumors while the other drugs aim to damage tumor DNA or block cell growth.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A (TAS-102, ramucirumab)Experimental Treatment3 Interventions
Patients receive TAS-102 PO BID on days 1-5 and 8-12, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Group II: Arm B (paclitaxel, ramucirumab)Active Control3 Interventions
Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Paclitaxel is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Taxol for:
- Ovarian cancer
- Breast cancer
- Non-small cell lung cancer
- Kaposi's sarcoma
🇪🇺 Approved in European Union as Taxol for:
- Ovarian cancer
- Breast cancer
- Non-small cell lung cancer
- Kaposi's sarcoma
🇨🇦 Approved in Canada as Paclitaxel for:
- Ovarian cancer
- Breast cancer
- Non-small cell lung cancer
- Kaposi's sarcoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Alabama at Birmingham Cancer CenterBirmingham, AL
USC / Norris Comprehensive Cancer CenterLos Angeles, CA
Mayo Clinic in FloridaJacksonville, FL
Cleveland Clinic-WestonWeston, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Academic and Community Cancer Research UnitedLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Trifluridine/Tipiracil: A Review in Metastatic Gastric Cancer. [2020]Trifluridine/tipiracil (Lonsurf®) is a fixed-dose combination tablet comprising trifluridine, an antineoplastic nucleoside analogue, and tipiracil, a thymidine phosphorylase inhibitor. Trifluridine/tipiracil has recently been granted an additional indication in the USA for the treatment of metastatic gastric cancer, including gastroesophageal junction adenocarcinoma, in patients who have been previously treated with at least two systemic treatment regimens, and has received a positive opinion for this indication in the EU. In the large pivotal phase III TAGS trial, trifluridine/tipiracil plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) compared with placebo plus BSC in this patient group. Progression-free survival (PFS) and the disease control rate were also improved with trifluridine/tipiracil relative to placebo. Health-related quality of life was not adversely affected by the addition of trifluridine/tipiracil to BSC and time to deterioration of Eastern Cooperative Oncology Group (ECOG) performance status was significantly delayed. The most common adverse events were mainly haematological (neutropenia, leucopenia and anaemia) and gastrointestinal (nausea, vomiting and diarrhoea), and were generally manageable with dosage modifications and/or supportive care. Adverse events ≥ Grade 3 were most frequently haematological in nature. Thus, trifluridine/tipiracil provides a valuable and much needed treatment option for patients with metastatic gastric or gastroesophageal junction adenocarcinoma that has progressed on at least two prior therapies.
Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study. [2023]Ramucirumab-alone or combined with paclitaxel-represents one of the main options for patients failing first-line treatment for advanced gastric cancer.
[Clinical Experience of Ramucirumab for Treating Advanced Gastric Cancer]. [2023]The REGARD and RAINBOW trials showed that ramucirumab(RAM)alone and RAM plus paclitaxel(PTX) were effective therapies for advanced gastric cancer patients previously treated with chemotherapy. In this retrospective study, we evaluated the safety and efficacy of RAM alone and PTX plus RAM in such patients.
Clinical Evaluation of the Safety and Efficacy of Trifluridine/Tipiracil in the Treatment of Advanced Gastric/Gastroesophageal Junction Adenocarcinoma: Evidence to Date. [2020]Trifluridine/tipiracil or TAS-102 (Taiho Oncology, Lonsurf®, Princeton, NJ, USA) is a combination tablet of trifluridine, a thymidine-based nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor, in a 1:0.5 molar ratio. This drug was first approved for use in metastatic colorectal cancer patients. Recently, the U S Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted approval of trifluridine/tipiracil for treatment of metastatic gastric and gastroesophageal junction adenocarcinoma in patients following at least two lines of chemotherapy including fluoropyrimidine and platinum chemotherapy agents, as well as taxanes or irinotecan. This approval was granted after the findings from first a Phase II trial (EPOC1201) investigating trifluridine/tipiracil, and later a global Phase III trial (TAGS trial) that compared trifluridine/tipiracil vs placebo with best supportive care. Both trials primarily utilized trifluridine/tipiracil at a dose of 35 mg/m2 twice daily. In the EPOC1201 trial, the primary end point of disease control rate was greater than 50% after eight weeks of therapy. The most common grade three or four adverse event was neutropenia; additional toxicities included leukopenia, anemia, and anorexia. In the TAGS trial, overall survival in patients treated with trifluridine/tipiracil (5.7 months) was significantly improved as compared to the placebo-controlled group (3.6 months). Treatment with trifluridine/tipiracil not only did not impair quality of life but also tended to reduce the risk of deterioration of quality of life. The results of these studies along with the subsequent FDA and EMA approval have generated an important breakthrough in regard to treatment options for patients with refractory metastatic gastric or gastroesophageal junction adenocarcinoma.
Efficacy and safety of trifluridine/tipiracil plus ramucirumab in comparison with trifluridine/tipiracil monotherapy for patients with advanced gastric cancer-single institutional experience. [2023]Trifluridine/tipiracil plus VEGF inhibition with ramucirumab (RAM) for advanced gastric cancer (AGC) demonstrated clinical activity with an acceptable toxicity profile in previous phase II trial. However, little is known about its efficacy and safety in clinical practice in comparison with trifluridine/tipiracil monotherapy.
Safety and activity of trifluridine/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial. [2023]Findings of preclinical and clinical trials in colorectal cancer have shown promising antitumour effects of the co-formulation trifluridine/tipiracil and VEGF inhibition. We aimed to investigate the safety and activity of trifluridine/tipiracil and ramucirumab for previously treated advanced gastric cancer.
Trifluridine/tipiracil for the treatment of metastatic gastric cancer. [2020]Introduction: Trifluridine/tipiracil is a novel oral cytotoxic chemotherapy consisting of a thymidine-based nucleoside analog, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil. Trifluridine/tipiracil was approved for the treatment of metastatic colorectal cancer refractory to standard therapies. A phase II trial in Japan demonstrated that this therapy has antitumor activity and is tolerated by patients with advanced gastric cancer (AGC); as a result, the phase III TAGS trial (Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer) was initiated.Area covered: Trifluridine/tipiracil has proved effective for heavily pretreated AGC and has thus been approved for use in the United States in February 2019, Japan in August 2019 and the European Union in September 2019. Detail of the phase III TAGS trial is discussed in this review.Expert opinion: Trifluridine/tipiracil after at least two previous courses of systemic chemotherapy improved rates of survival of gastric cancer; thus it has become one of the treatment options in affected patients. Currently, several clinical trials of trifluridine/tipiracil in combination with other anticancer agents such as ramucirumab (an anti-vascular endothelial growth factor receptor 2 monoclonal antibody) for patients with AGC are ongoing.
A case of ramucirumab-related gastrointestinal perforation in gastric cancer with small bowel metastasis. [2020]Ramucirumab is a monoclonal antibody targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Ramucirumab either alone or in combination with paclitaxel (PTX) has been found to be safe and effective for patients with previously treated advanced gastric cancer. One of the serious adverse events associated with ramucirumab is gastrointestinal (GI) perforation.
Placental growth factor is a predictive biomarker for ramucirumab treatment in advanced gastric cancer. [2023]Ramucirumab (RAM) has been used as the second-line standard chemotherapy for advanced gastric cancer (AGC) either alone or combination with paclitaxel (PTX). However, no predictive biomarkers have been identified for RAM treatment in AGC.