Chemotherapy + Bevacizumab for Metastatic Colorectal Cancer
(SCOTI Trial)
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Rutgers, The State University of New Jersey
Must not be taking: Investigational agents
Disqualifiers: TAS-102, CNS metastases, active malignancy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study is to evaluate the disease control rate and time to progression of the sequential combination of oxaliplatin with an alternative anti-metabolite Trifluridine/tipiracil hydrochloride mixture, TAS-102,(TAS-OX) as well as irinotecan in combination with TAS-102 oxaliplatin(TAS-OX) + Bevacizumab in late-line metastatic colorectal cancer (mCRC)
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently on other investigational agents or have had anticancer therapy within the last two weeks.
What data supports the effectiveness of the drug combination of chemotherapy and Bevacizumab for metastatic colorectal cancer?
Research shows that combining irinotecan with other chemotherapy drugs like fluorouracil and leucovorin significantly improves survival rates in metastatic colorectal cancer patients. Additionally, the combination of trifluridine/tipiracil (TAS-102) with bevacizumab has been shown to be effective and safe for treating this condition.
12345Is the combination of chemotherapy and Bevacizumab safe for treating metastatic colorectal cancer?
The combination of chemotherapy drugs like Irinotecan and Oxaliplatin with Bevacizumab has been studied for safety in treating metastatic colorectal cancer. Common side effects include anemia (low red blood cell count), neutropenia (low white blood cell count), fatigue, nausea, and diarrhea. These side effects were generally manageable, but some patients needed dose adjustments or stopped treatment due to these reactions.
15678What makes the drug combination of chemotherapy and bevacizumab unique for metastatic colorectal cancer?
This drug combination is unique because it includes TAS-102 (trifluridine/tipiracil), which is used with bevacizumab to treat patients who are not eligible for intensive therapy, offering an alternative for those who have not responded to standard treatments. The combination has shown efficacy in improving survival rates in patients with metastatic colorectal cancer.
59101112Eligibility Criteria
This trial is for adults with stage IV colon cancer that's worsened after standard treatments, including chemotherapy and antibody therapy. Candidates must have normal albumin levels, measurable disease progression, acceptable organ function, and a life expectancy of at least three months. Pregnant or breastfeeding individuals, those with severe allergies to the drugs used in this study or certain medical conditions are excluded.Inclusion Criteria
I am 18 years old or older.
I can take pills by mouth.
Progression of disease documented on the most recent scan
+11 more
Exclusion Criteria
I have previously taken the medication TAS-102.
I need treatment for cancer that has spread to my brain and is causing symptoms.
I couldn't handle irinotecan before because it caused severe diarrhea.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive TAS-102, oxaliplatin, irinotecan with bevacizumab in alternating cycles until disease progression or adverse events
Until disease progression or adverse events
14-day cycles with in-person visits on day 1 of each cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 100 months
Participant Groups
The study tests a sequential combination treatment for metastatic colorectal cancer using TAS-102 alternated with oxaliplatin (TAS-OX) and irinotecan plus bevacizumab. It aims to assess how well the disease is controlled and how long before it progresses.
1Treatment groups
Experimental Treatment
Group I: Tolerability of TAS-102, oxaliplatin, irinotecan with bevacizumabExperimental Treatment1 Intervention
Each treatment cycle will be fourteen days long. TAS-102 25 mg/m2 will be taken orally twice daily on days 1-5 of each cycle. Oxaliplatin 85 mg/m2 infusion will be given on day one for one cycle alternating with Irinotecan 150 mg/m2 infusion, which will be given on day one the next cycle.
Irinotecan is already approved in United States, European Union, Japan, Canada for the following indications:
🇺🇸 Approved in United States as Camptosar for:
- Colorectal cancer
🇪🇺 Approved in European Union as Irinotecan for:
- Colorectal cancer
🇯🇵 Approved in Japan as Topotecin for:
- Colorectal cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Irinotecan for:
- Colorectal cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
RWJBarnabas Health - Robert Wood Johnson University HospitalSomerset, NJ
RWJBarnabas Health - Monmouth Medical Center Southern CampusLakewood, NJ
RWJBarnabas Health - Community Medical CenterToms River, NJ
RWJBarnabas Health Jersey City Medical CenterJersey City, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
Rutgers, The State University of New JerseyLead Sponsor
References
A National Cancer Institute of Canada Clinical Trials Group Study--IND.135: Phase I/II study of irinotecan (camptosar), oxaliplatin and raltitrexed (tomudex) (COT) in patients with advanced colorectal cancer. [2018]Thirty-one patients with metastatic colorectal cancer were enrolled in this phase I/II trial of a triple combination of camptosar (C), oxaliplatin (O) and tomudex (T), all given on day one of a convenient three-week schedule. Patients received 257 cycles (1-18) in five cohorts. Toxicity was manageable and haematological toxicity was mild to moderate. Diarrhoea was the main dose-limiting toxicity; nausea and vomiting were common. Fatigue was frequent, moderate in severity and a reason for discontinuation in some patients. The recommended phase II doses were (C) 220 mg/m(2), (O) 100mg/m(2), (T) 2.75 mg/m(2). A 50% response rate in 30 evaluable patients was confirmed by an independent radiology review board; progression-free survival and overall median survival were 7.3 months and 16.6 months, respectively. Of the 16 patients treated at the recommended dose, 9 (56.3%) experienced partial response. Further evaluation in a randomized study compared to sequential doublets is warranted. Triple combinations could be relevant in curative settings for high-risk patients.
Developments in combination chemotherapy for colorectal cancer. [2018]In the last 5 years, major advances have occurred in the treatment of colorectal cancer. Following a period of over 30 years in which 5-fluorouracil was the only proven treatment for colorectal cancer, survival for patients with metastatic colorectal cancer has nearly doubled following the introduction of irinotecan (Campto, Aventis) and oxaliplatin (Eloxatin, Sanofi-Synthelabo). Furthermore, recent studies have demonstrated additional improvements in response and survival when combination chemotherapy drugs are administered with biologic agents that target angiogenesis and tumor growth pathways. The benefit of these newer drugs is now being realized in the adjuvant setting, where the addition of oxaliplatin to infusional 5-fluorouracil/leucovrin has led to improvements in disease-free survival. Further adjuvant studies are testing the benefit of the addition of biologic therapies to oxaliplatin and irinotecan-based combination chemotherapy.
European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. [2018]Tremendous progress has been made in the medical treatment of advanced colorectal cancer during the past 2 to 3 years, due to the availability of several new drugs. Of these new agents, irinotecan (CPT-11 [Camptosar]) seems to be one of the most active against advanced colorectal cancer. It is, therefore, a good candidate for combination with the more classic cytotoxic agents for this disease. This article summarizes several European phase I and II studies in which irinotecan has been combined with (1) fluorouracil (5-FU) alone, given as a repeated bolus injection or a protracted infusion; (2) 5-FU modulated by folinic acid (leucovorin) according to different schedules; or (3) mitomycin (Mutamycin). All of these studies have demonstrated clinical responses in patients with advanced colorectal carcinoma, including complete responses. The toxicity profiles of the various combinations seem to be acceptable; neutropenia and delayed diarrhea are the most frequent side effects. Large phase III studies are still warranted to demonstrate the benefit of these irinotecan-based regimens.
Irinotecan and high-dose fluorouracil/leucovorin for metastatic colorectal cancer. [2018]Two randomized phase III trials with irinotecan as second-line treatment of metastatic colorectal cancer have shown that irinotecan (CPT-11, Camptosar) significantly improves survival when compared with best supportive care or continuous infusion of fluorouracil (5-FU) after failure of 5-FU. The combination of irinotecan and 5-FU/leucovorin produced a significantly higher response rate (40.8% vs 23.1%, P
Prospective Multicenter Phase II Study of Biweekly TAS-102 and Bevacizumab for Metastatic Colorectal Cancer. [2021]This study assessed the efficacy and safety of biweekly trifluridine and tipiracil hydrochloride (TAS-102) with bevacizumab combination therapy for patients with metastatic colorectal cancer (mCRC).
FDA Approval Summary: TAS-102. [2022]The FDA approved TAS-102 (Lonsurf; Taiho Oncology, Inc.) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF biological therapy; and if RAS wild type, an anti-EGFR therapy. In an international, multicenter, double-blinded, placebo-controlled trial (TPU-TAS-102-301, herein referred to as RECOURSE), 800 patients with previously treated mCRC were randomly allocated (2:1) to receive either TAS-102 35 mg/m2 orally twice daily after meals on days 1 through 5 and 8 through 12 of each 28-day cycle (n = 534) or matching placebo (n = 266). The trial demonstrated a statistically significant improvement in overall survival for those randomized to receive TAS-102, with a median survival of 7.1 months in the TAS-102 arm [confidence interval (CI), 6.5-7.8] and 5.3 months in the placebo arm [CI, 4.6-6.0; hazard ratio (HR), 0.68; 95% CI, 0.58-0.81; P < 0.001, stratified log-rank test]. The trial also demonstrated a statistically significant prolongation of progression-free survival (HR, 0.47; 95% CI, 0.40-0.55; P < 0.001). The most common adverse reactions, in order of decreasing frequency, observed in the patients who received TAS-102 were anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, and pyrexia. Adverse events led to discontinuation of TAS-102 in 3.6% of patients, and 13.7% required a dose reduction. The most common adverse reactions leading to dose reduction were neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea. Clin Cancer Res; 23(12); 2924-7. ©2017 AACR.
Metastatic Colorectal Cancer: Management With Trifluridine/Tipiracil . [2017]Treatment-related adverse events (AEs) are common in patients with metastatic colorectal cancer (mCRC) receiving chemotherapy. These AEs may affect patient adherence, particularly with completely oral regimens, such as trifluridine/tipiracil (TAS-102, Lonsurf®), an antimetabolite agent for patients with mCRC refractory or intolerant to standard therapies. .
An Exploration of Trifluridine/Tipiracil Monotherapy and in Combination With Bevacizumab or Immune Checkpoint Inhibitors for Patients With Metastatic Colorectal Cancer: A Real-World Study. [2023]Trifluridine/tipiracil (TAS-102) has achieved modest efficacy in the late-line treatment of metastatic colorectal cancer. The present study aimed to explore the clinical efficacy and drug toxicities of TAS-102 for patients with metastatic colorectal cancer in real-world clinical setting.
Trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study. [2023]Trifluridine-tipiracil plus bevacizumab has shown efficacy in previous phase 2 studies including patients with unresectable metastatic colorectal cancer. We aimed to investigate first-line trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab in patients with unresectable metastatic colorectal cancer ineligible for intensive treatment.
Efficacy, safety and prognostic factors in patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil plus bevacizumab in a real-world setting. [2022]We evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab in treating refractory metastatic colorectal cancer (mCRC) in a retrospective, observational study. Patients refractory or intolerant to standard therapies received TAS-102 (30-35 mg/m2 twice daily on days 1-5 and days 8-12 every 28 days) plus bevacizumab 5 mg/kg on days 1 and 15. Clinical and pathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) data were collected and analysed. Thirty-five patients were treated from July 2019 to October 2021 (median age 64 years). The majority of patients (68.6%) were receiving TAS-102 plus bevacizumab as third-line treatment. Patients received a median of 4 (range 2-15) cycles of treatment. Among 31 patients evaluable for response (88.6%), ORR and DCR were 3.2% and 51.6%, respectively. After a median 11.6 months' follow-up, median PFS was 4.3 (95% confidence interval [CI] 3.4-5.1) months and median OS was 9.3 (95% CI 6.6-12.1) months. The most common grade 3-4 toxicities were neutropenia, asthenia and nausea/vomiting, and there were no treatment-related deaths. This real-world study confirms the efficacy and safety of TAS-102 plus bevacizumab in patients with refractory mCRC.
[Anti-angiogenic treatment and colorectal cancer]. [2015]For many years, oncology research has focused on the study of therapeutic agents able to target a different cell than a cancer cell. Tumor angiogenesis mediated by the vascular endothelial growth factor (VEGF) was one of the pathways investigated. The treatment of metastastic colorectal cancer has dramatically evolved. Overall survival has significantly improved, owing to the use in standard daily practice of irinotecan and oxaliplatin, combined with 5-fluorouracil (5FU) and leucovorin. This review summarizes efficacy and safety data of two antiangiogenic agents, bevacizumab (a monoclonal antibody inhibiting VEGF) and vatalanib (a tyrosine kinase inhibitor of VEGF), assessed in phase III trials in metastastic colorectal cancer. The efficacy of bevacizumab combined with 5FU-leucovorin +/- irinotecan based on overall survival data which was demonstrated in the first-line treatment of metastastic colorectal cancer in studies conducted in the US, has recently been demonstrated in the same indication based on progression survival when combined to oxaliplatin and a fluoropyrimidine (capecitabine or 5FU-leucovorin). Bevacizumab combined to infusion chemotherapy with 5FU-leucovorin with or without irinotecan is indicated, in Europe, in the first-line treatment of metastastic colorectal cancer. While in the US, prescription options are wider in the first-line treatment, it is combined to chemotherapies with a fluoropyrimidine +/- irinotecan or oxaliplatin, and in second line as well with fluoropyrimidine and oxaliplatin. Several questions regarding the optimal use of bevacizumab still remain to be answered in the treatment of metastastic colorectal cancer. Vatalanib has not shown benefit in this pathology.
Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study. [2022]We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies.