Metastatic Colorectal Cancer (CRC)Phase 2NCT07042685
Trial of 5-Fluorouracil (5FU)-Based Therapy in Combination With Fruquintinib in Patients With Locally Advanced Unresectable or Metastatic Colorectal Cancer
A Phase 2 study testing Fruquintinib Combined With Chemotherapy in people with Metastatic Colorectal Cancer (CRC), run by The Methodist Hospital Research Institute at 1 site in United States.
Trial summary
This Phase II clinical trial at Houston Methodist Neal Cancer Center is evaluating the safety and efficacy of combining 5-Fluorouracil (5FU) -based chemotherapy (either FOLFIRI: folinic acid, 5FU, irinotecan; or mFOLFOX6: folinic acid, 5FU, oxaliplatin) with fruquintinib as a first-line treatment for patients with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer (CRC)
- What is being tested?
- Fruquintinib Combined With Chemotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2026to Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥18 years of age.
- Written informed consent is required before performing any trial-specific tests or procedures. Signing of the informed consent form can occur outside the 28-day screening period.
- Histopathologically or cytologically confirmed locally advanced unresectable or metastatic colorectal cancer. The study will include an all-comer population, meaning that patients will not be excluded based on specific molecular markers such as microsatellite instability-high (MSI-H) or B-Raf proto-oncogene mutations (BRAF mutations). However, as part of the Standard of Care, comprehensive molecular testing will be performed to assess MSI status, and other relevant biomarkers. For patients with MSI-H or BRAF mutations confirmed, treatment may be adjusted per Standard of Care practices.
- Measurable disease per RECISTv1.1.
- No prior systemic treatment. Patients with resected disease who later develop unresectable recurrence without prior systemic therapy remain eligible.
- ECOG performance status of 0 or 1.
Show all 9Show fewer
- Life expectancy ≥6 months per treating physician's assessment.
- Patients of childbearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose of study treatment.
- Patients must be able to swallow oral tablets.
Who cannot join
- Hematology laboratory values of:
- Absolute neutrophil count ≤1500 cells/mm3
- Platelets ≤100,000 cells/mm3
- Hemoglobin ≤9 g/dL
- White blood count ≤3000 cells/mm3.
- Hepatic laboratory values of aspartate transaminase (AST) or alanine aminotransferase (ALT):
Show all 39Show fewer
- >5 × upper limits of normal (ULN) if the documented history of hepatic metastases; or
- >2.5 × ULN if no liver metastases are present.
- Serum albumin <2.8 g/dL.
- Total bilirubin >1.7 mg/dL × ULN.
- Prothrombin time (PT) or international normalized ratio (INR) >1.5 × ULN. Note: Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible if PT and INR are within the acceptable institutional therapeutic limits.
- Serum creatinine or serum urea >1.5 × ULN.
- Estimated glomerular filtration rate <50 mL/min.
- Urine dipstick or urinalysis with protein ≥2+ or 24-hour urine protein ≥1.0 g/24-h. Subjects with 1+ proteinuria must undergo a 24-hour urine collection to assess urine protein level.
- Positive pregnancy test, pregnant, or breastfeeding for all women of child-bearing potential.
- Per treating physician's assessment, any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study.
- Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study including, but not limited to:
- Arrhythmia
- Bradycardia
- Tachycardia
- Symptomatic valvular disease
- Symptomatic congestive heart failure is classified by the New York Heart Association as Class III or IV
- Unstable angina pectoris.
- Myocardial infarction within the past 6 months from consent.
- Active bleeding diathesis.
- Current complaints of persistent constipation or history of chronic constipation, untreatable bowel obstruction, or fecaloma within the past 6 months from consent.
- Receiving chronic treatment with corticosteroids ≥5 mg of prednisone per day (or equivalent) or other systemic immunosuppressive agents. Topical or nasal corticosteroids are allowed.
- Known history and/or uncontrolled hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV)-1 or HIV-2.
- History of galactose intolerance, deficiency of Lapp lactase, or glucose-galactose malabsorption.
- History of malignancy or active treatment for malignancy other than CRC (i.e., radiation or chemotherapy, including monoclonal antibodies) within 5 years. Note: Patients with squamous or basal cell carcinomas of the skin, carcinomas in situ of the cervix or uterus, ductal breast cancer in situ, resected low-grade prostate cancer, or other malignancies that in the opinion of the investigator are considered cured may participate.
- Receipt of live, attenuated vaccine (e.g., intranasal influenza, measles, mumps, rubella, varicella) or close contact with someone who has received a live, attenuated vaccine within the past 1 month from consent. Note: Influenza vaccine will be allowed if administered >21 days.
- Receipt of any investigational agent or study treatment within the past 30 days from consent for a condition other than CRC.
- Receipt of any protein or antibody-based therapeutic agents (e.g., growth hormones or monoclonal antibodies) within the past 3 months from consent for a condition other than CRC.
- Uncontrolled hypertension
- Active infection requiring treatment
- Recent history of major surgery
- Thromboembolic events during the past 6 months
- Adults unable to consent
- Prisoners
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Houston Methodist Neal Cancer Center
Houston, Texas, 77030
Maen Abdelrahim, MD, PhD, Pharm B, 713-441-1240, mabdelrahim@houstonmethodist.org
Abdullah Esmail, MD, AEsmail@houstonmethodist.org
About this study
Official title: Phase II Trial of 5-Fluorouracil (5FU)-Based Therapy in Combination With Fruquintinib as First Line in Patients With Locally Advanced Unresectable or Metastatic Colorectal Cancer
This Phase II clinical trial at Houston Methodist Neal Cancer Center is evaluating the safety and efficacy of combining 5-Fluorouracil (5FU) -based chemotherapy (either FOLFIRI: folinic acid, 5FU, irinotecan; or mFOLFOX6: folinic acid, 5FU, oxaliplatin) with fruquintinib as a first-line treatment for patients with locally advanced unresectable or metastatic colorectal cancer. Fifty patients will receive treatment in 28-day cycles, with fruquintinib initially dosed at 4 mg daily and potentially increased to 5 mg if no significant toxicities are observed. After six months, patients showing stable disease or better will transition to a maintenance phase with 5FU and fruquintinib, continuing until disease progression or other discontinuation criteria are met. The primary endpoint is time to progression based on RECIST v1.1 criteria, while secondary endpoints include safety, tolerability, and duration of response. The trial is being conducted across multiple Houston Methodist hospitals and is currently the only first-line CRC trial available in the system. If successful, it could offer a new therapeutic option and inform future treatment guidelines for advanced colorectal cancer.
Read the detailed description
This is a phase II trial investigating the efficacy and safety of 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib for patients with locally advanced unresectable or metastatic colorectal cancer in the first-line setting at Houston Methodist Neal Cancer Center. Patients will be administered 5FU-based therapy combined with fruquintinib. This study will consist of the 5FU-based therapy administered to 50 patients as FOLFIRI (Irinotecan: 180mg/ m² I.V. 30-90min day 1, LV: 400mg/ m² I.V. 2 hours day 1, 5FU: 400mg/ m² I.V. bolus day 1; 2400mg/ m² I.V. 46-48 hours, in 2 weeks cycle), or mFOLFOX6 (Oxaliplatin: 85mg/ m² I.V. 2 hours day 1, LV: 400mg/ m² I.V. 2hours day1, 5FU: 400mg/ m² I.V. bolus day 1; 2400mg/m 2 I.V. 46-48 hours, in 2 weeks cycle), and fruquintinib orally once daily on days 1-21.The first 3 patients will receive fruquintinib at 4 mg orally once daily of each cycle. If no dose-limiting toxicity (DLT)-like adverse events related to fruquintinib are observed during the first two cycles, then subsequent patients will be enrolled at 5 mg orally once daily. Both fruquintinib and 5FU-based therapy doses will be adjusted as needed according to the Principal Investigator's opinion. Treatments will be 28-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. After six months on the trial treatment, patients who have stable disease, partial response or complete response will transition to maintenance therapy which consists of 5-FU and fruquintinib, continuing until disease progression, unacceptable toxicity, or consent withdrawal. Following the study treatment period, patients who maintain a favorable response will be offered to continue the trial regimen off-protocol. The total study duration is approximately 12 months which encompasses both the initial treatment phase (6 cycles/6months) and the maintenance phase. There is no pre-specified maximum duration for the maintenance phase; treatment will continue until disease progression, unacceptable toxicity, or patient withdrawal. This ensures that patients deriving clinical benefit from the therapy can continue treatment as long as it remains safe and effective.
The primary endpoint will be evaluating the time to progression (TTP) of the patient population according to RECIST v1.1 criteria. A secondary endpoint will be assessing the safety and tolerability of 5FU-based therapy in combination with fruquintinib, as measured through the incidence and severity of treatment-emergent AEs (NCI CTCAE (v5.0)) and change from baseline in the clinical laboratory and physical examination findings. All grades of adverse event rates will be assessed and reported. An additional secondary endpoint will be measuring the duration of response of 5FU-based treatment in combination with fruquintinib in a first-line setting for locally advanced unresectable or metastatic colorectal cancer patients according to RECIST v1.1 criteria and using the investigator's tumor assessment. This study will be conducted within the Houston Methodist System including the Neal Cancer Center with full access to the naïve treatment population at other Houston Methodist community hospitals such as Houston Methodist Baytown Hospital, Houston Methodist Sugar Land Hospital, Houston Methodist Willowbrook Hospital, Houston Methodist West Hospital, Houston Methodist Clear Lake Hospital, Houston Methodist Cypress Hospital, and other Houston Methodist locations. Outreach materials such as brochures, fact sheets, flyers, and posters with our trial information will be compiled and distributed to our Houston Methodist Neal Cancer Center and Health System colleagues. Automated follow-up emails or text messages will remind patients to take the next step with their providers.
This study has no competing trial active at the Houston Methodist System, including the Neal Cancer Center or other community hospitals, making this the only first-line CRC trial available. If successful, the proposed therapy will represent a new option, in the first-line setting, for the treatment of locally advanced unresectable or metastatic colorectal cancer. This single-arm study may provide insights that could inform future guidelines enabling studies to better treat and control CRC.
- Conditions
- Metastatic Colorectal Cancer (CRC)
- Being tested
- Fruquintinib Combined With Chemotherapy
- Keywords
- first line, CRC, metastatic
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fruquintinib Combined With ChemotherapyDrug
Also called Fruquintinib
The intervention in this trial involves administering a combination of 5FU-based chemotherapy and fruquintinib to patients with locally advanced unresectable or metastatic colorectal cancer. Patients receive either the FOLFIRI or mFOLFOX6 regimen, both of which include 5-fluorouracil (5FU), leucovorin (LV), and either irinotecan (FOLFIRI) or oxaliplatin (mFOLFOX6). Fruquintinib is given orally once daily for 21 days in each 28-day cycle. The initial dose of fruquintinib is 4 mg daily for the first three patients to assess safety; if no dose-limiting toxicities are observed, the dose is increased to 5 mg daily for subsequent participants. Treatment continues until disease progression, unacceptable toxicity, or patient withdrawal. After six months, patients with stable disease or better transition to a maintenance phase with 5FU and fruquintinib alone.
| Study group | Role | What they receive |
|---|---|---|
| 5FU-based chemotherapy (FOLFIRI or mFOLFOX6) with fruquintinib | Experimental | The trial includes a single treatment arm in which all enrolled patients receive a combination of 5-Fluorouracil (5FU)-based chemotherapy and fruquintinib. Patients are treated with either the FOLFIRI or mFOLFOX6 (FOLFIRI: folinic acid, 5FU, irinotecan; or mFOLFOX6: folinic acid, 5FU, oxaliplatin) regimen, both of which include 5-fluorouracil (5FU), leucovorin (LV), and either irinotecan or oxaliplatin, respectively. Fruquintinib is administered orally once daily for 21 days of each 28-day cycle. The initial three patients receive 4 mg of fruquintinib daily to assess safety; if no dose-limiting toxicities are observed, the dose is increased to 5 mg for subsequent patients. Treatment continues until disease progression, unacceptable toxicity, or patient withdrawal. After six months, patients with stable disease or better transition to a maintenance phase with 5FU and fruquintinib alone. Receives: Drug: Fruquintinib Combined With Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients
To assess the time to progression (TTP) of patients with locally advanced unresectable or metastatic colorectal cancer (mCRC) treated with 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib, according to RECIST v1.1 criteria.
Measured: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 24 months.
Secondary outcomes (2)
Incidence of toxicity of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients
To assess the safety profile, toxicity (all grades of adverse event rates) of 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib in patients with locally advanced unresectable or metastatic colorectal cancer (mCRC) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Measured: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws from the study, whichever came first, assessed up to 13 months.
Duration of the response of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients
To evaluate the duration of the response of 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib in the first-line setting for locally advanced unresectable or metastatic colorectal cancer (mCRC) patients from onset of response to progression or death, whichever occurs earlier according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria and investigator's tumor assessment.
Measured: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2025
- Study start27 Jan 2026
- Primary completionDec 2028 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal Cancer (CRC)Studies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Maen Abdelrahim, MD, PhD, Pharm D, Principal investigator, The Methodist Hospital Research InstituteAbdullah Esmail, MD, Study director, Houston Methodist Neal Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07042685
- Sponsor's protocol ID
- PRO00039815 (HMCC-GI25-001)
- Status last verified
- Apr 2026
- First submitted
- 20 Jun 2025
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Clinical Study Report will include analysis of de-identified data and will be shared with the supporter and published when available.
Publications
Sawicki T, Ruszkowska M, Danielewicz A, Niedzwiedzka E, Arlukowicz T, Przybylowicz KE. A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers (Basel). 2021 Apr 22;13(9):2025. doi: 10.3390/cancers13092025.
PubMed 33922197Biller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021 Feb 16;325(7):669-685. doi: 10.1001/jama.2021.0106.
PubMed 33591350Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002 Oct;2(10):795-803. doi: 10.1038/nrc909.
PubMed 12360282Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schutz G, Thierauch KH, Zopf D. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 2011 Jul 1;129(1):245-55. doi: 10.1002/ijc.25864. Epub 2011 Apr 22.
PubMed 21170960Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003 May;111(9):1287-95. doi: 10.1172/JCI17929.
PubMed 12727920Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter EJ, Chase A, Chessells JM, Colombat M, Dearden CE, Dimitrijevic S, Mahon FX, Marin D, Nikolova Z, Olavarria E, Silberman S, Schultheis B, Cross NC, Goldman JM. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med. 2002 Aug 15;347(7):481-7. doi: 10.1056/NEJMoa020150.
PubMed 12181402Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, Yang L, Deng Y, Chen ZD, Zhong H, Pan H, Guo W, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Chen D, Li W, Sun S, Yu Z, Cao P, Chen H, Wang J, Wang S, Wang H, Fan S, Hua Y, Su W. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018 Jun 26;319(24):2486-2496. doi: 10.1001/jama.2018.7855.
PubMed 29946728Dasari A, Lonardi S, Garcia-Carbonero R, Elez E, Yoshino T, Sobrero A, Yao J, Garcia-Alfonso P, Kocsis J, Cubillo Gracian A, Sartore-Bianchi A, Satoh T, Randrian V, Tomasek J, Chong G, Paulson AS, Masuishi T, Jones J, Csoszi T, Cremolini C, Ghiringhelli F, Shergill A, Hochster HS, Krauss J, Bassam A, Ducreux M, Elme A, Faugeras L, Kasper S, Van Cutsem E, Arnold D, Nanda S, Yang Z, Schelman WR, Kania M, Tabernero J, Eng C; FRESCO-2 Study Investigators. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. 2023 Jul 1;402(10395):41-53. doi: 10.1016/S0140-6736(23)00772-9. Epub 2023 Jun 15.
PubMed 37331369Mohelnikova-Duchonova B, Melichar B, Soucek P. FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy. World J Gastroenterol. 2014 Aug 14;20(30):10316-30. doi: 10.3748/wjg.v20.i30.10316.
PubMed 25132748Ishiguro M, Kotake K, Nishimura G, Tomita N, Ichikawa W, Takahashi K, Watanabe T, Furuhata T, Kondo K, Mori M, Kakeji Y, Kanazawa A, Kobayashi M, Okajima M, Hyodo I, Miyakoda K, Sugihara K. Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer. BMC Cancer. 2013 Mar 25;13:149. doi: 10.1186/1471-2407-13-149.
PubMed 23530572Reddy TP, Khan U, Burns EA, Abdelrahim M. Chemotherapy rechallenge in metastatic colon cancer: A case report and literature review. World J Clin Oncol. 2020 Nov 24;11(11):959-967. doi: 10.5306/wjco.v11.i11.959.
PubMed 33312889Glimelius B, Stintzing S, Marshall J, Yoshino T, de Gramont A. Metastatic colorectal cancer: Advances in the folate-fluoropyrimidine chemotherapy backbone. Cancer Treat Rev. 2021 Jul;98:102218. doi: 10.1016/j.ctrv.2021.102218. Epub 2021 May 4.
PubMed 34015686Vogel A, Hofheinz RD, Kubicka S, Arnold D. Treatment decisions in metastatic colorectal cancer - Beyond first and second line combination therapies. Cancer Treat Rev. 2017 Sep;59:54-60. doi: 10.1016/j.ctrv.2017.04.007. Epub 2017 May 4.
PubMed 28738235Diez M, Teule A, Salazar R. Gastroenteropancreatic neuroendocrine tumors: diagnosis and treatment. Ann Gastroenterol. 2013;26(1):29-36.
PubMed 24714698Colucci G, Gebbia V, Paoletti G, Giuliani F, Caruso M, Gebbia N, Carteni G, Agostara B, Pezzella G, Manzione L, Borsellino N, Misino A, Romito S, Durini E, Cordio S, Di Seri M, Lopez M, Maiello E, Montemurro S, Cramarossa A, Lorusso V, Di Bisceglie M, Chiarenza M, Valerio MR, Guida T, Leonardi V, Pisconti S, Rosati G, Carrozza F, Nettis G, Valdesi M, Filippelli G, Fortunato S, Mancarella S, Brunetti C; Gruppo Oncologico Dell'Italia Meridionale. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale. J Clin Oncol. 2005 Aug 1;23(22):4866-75. doi: 10.1200/JCO.2005.07.113. Epub 2005 Jun 6.
PubMed 15939922
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of 5-Fluorouracil (5FU)-Based Therapy in Combination With Fruquintinib as First Line in Patients With Locally Advanced Unresectable or Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT07042685
- Acronym / sponsor ID
- PRO00039815 (HMCC-GI25-001)
- Conditions
- Metastatic Colorectal Cancer (CRC)
- Keywords
- first line, CRC, metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Takeda Development Center Americas, Inc.
- Study start
- 27 Jan 2026 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 29 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase II clinical trial at Houston Methodist Neal Cancer Center is evaluating the safety and efficacy of combining 5-Fluorouracil (5FU) -based chemotherapy (either FOLFIRI: folinic acid, 5FU, irinotecan; or mFOLFOX6: folinic acid, 5FU, oxaliplatin) with fruquintinib as a first-line treatment for patients with locally advanced unresectable or metastatic colorectal cancer. Fifty patients will receive treatment in 28-day cycles, with fruquintinib initially dosed at 4 mg daily and potentially increased to 5 mg if no significant toxicities are observed. After six months, patients showing stable disease or better will transition to a maintenance phase with 5FU and fruquintinib, continuing until disease progression or other discontinuation criteria are met. The primary endpoint is time to progression based on RECIST v1.1 criteria, while secondary endpoints include safety, tolerability, and duration of response. The trial is being conducted across multiple Houston Methodist hospitals and is currently the only first-line CRC trial available in the system. If successful, it could offer a new therapeutic option and inform future treatment guidelines for advanced colorectal cancer.
Detailed description
This is a phase II trial investigating the efficacy and safety of 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib for patients with locally advanced unresectable or metastatic colorectal cancer in the first-line setting at Houston Methodist Neal Cancer Center. Patients will be administered 5FU-based therapy combined with fruquintinib. This study will consist of the 5FU-based therapy administered to 50 patients as FOLFIRI (Irinotecan: 180mg/ m² I.V. 30-90min day 1, LV: 400mg/ m² I.V. 2 hours day 1, 5FU: 400mg/ m² I.V. bolus day 1; 2400mg/ m² I.V. 46-48 hours, in 2 weeks cycle), or mFOLFOX6 (Oxaliplatin: 85mg/ m² I.V. 2 hours day 1, LV: 400mg/ m² I.V. 2hours day1, 5FU: 400mg/ m² I.V. bolus day 1; 2400mg/m 2 I.V. 46-48 hours, in 2 weeks cycle), and fruquintinib orally once daily on days 1-21.The first 3 patients will receive fruquintinib at 4 mg orally once daily of each cycle. If no dose-limiting toxicity (DLT)-like adverse events related to fruquintinib are observed during the first two cycles, then subsequent patients will be enrolled at 5 mg orally once daily. Both fruquintinib and 5FU-based therapy doses will be adjusted as needed according to the Principal Investigator's opinion. Treatments will be 28-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. After six months on the trial treatment, patients who have stable disease, partial response or complete response will transition to maintenance therapy which consists of 5-FU and fruquintinib, continuing until disease progression, unacceptable toxicity, or consent withdrawal. Following the study treatment period, patients who maintain a favorable response will be offered to continue the trial regimen off-protocol. The total study duration is approximately 12 months which encompasses both the initial treatment phase (6 cycles/6months) and the maintenance phase. There is no pre-specified maximum duration for the maintenance phase; treatment will continue until disease progression, unacceptable toxicity, or patient withdrawal. This ensures that patients deriving clinical benefit from the therapy can continue treatment as long as it remains safe and effective.
The primary endpoint will be evaluating the time to progression (TTP) of the patient population according to RECIST v1.1 criteria. A secondary endpoint will be assessing the safety and tolerability of 5FU-based therapy in combination with fruquintinib, as measured through the incidence and severity of treatment-emergent AEs (NCI CTCAE (v5.0)) and change from baseline in the clinical laboratory and physical examination findings. All grades of adverse event rates will be assessed and reported. An additional secondary endpoint will be measuring the duration of response of 5FU-based treatment in combination with fruquintinib in a first-line setting for locally advanced unresectable or metastatic colorectal cancer patients according to RECIST v1.1 criteria and using the investigator's tumor assessment. This study will be conducted within the Houston Methodist System including the Neal Cancer Center with full access to the naïve treatment population at other Houston Methodist community hospitals such as Houston Methodist Baytown Hospital, Houston Methodist Sugar Land Hospital, Houston Methodist Willowbrook Hospital, Houston Methodist West Hospital, Houston Methodist Clear Lake Hospital, Houston Methodist Cypress Hospital, and other Houston Methodist locations. Outreach materials such as brochures, fact sheets, flyers, and posters with our trial information will be compiled and distributed to our Houston Methodist Neal Cancer Center and Health System colleagues. Automated follow-up emails or text messages will remind patients to take the next step with their providers.
This study has no competing trial active at the Houston Methodist System, including the Neal Cancer Center or other community hospitals, making this the only first-line CRC trial available. If successful, the proposed therapy will represent a new option, in the first-line setting, for the treatment of locally advanced unresectable or metastatic colorectal cancer. This single-arm study may provide insights that could inform future guidelines enabling studies to better treat and control CRC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5FU-based chemotherapy (FOLFIRI or mFOLFOX6) with fruquintinib | Experimental | Drug: Fruquintinib Combined With ChemotherapyThe trial includes a single treatment arm in which all enrolled patients receive a combination of 5-Fluorouracil (5FU)-based chemotherapy and fruquintinib. Patients are treated with either the FOLFIRI or mFOLFOX6 (FOLFIRI: folinic acid, 5FU, irinotecan; or mFOLFOX6: folinic acid, 5FU, oxaliplatin) regimen, both of which include 5-fluorouracil (5FU), leucovorin (LV), and either irinotecan or oxaliplatin, respectively. Fruquintinib is administered orally once daily for 21 days of each 28-day cycle. The initial three patients receive 4 mg of fruquintinib daily to assess safety; if no dose-limiting toxicities are observed, the dose is increased to 5 mg for subsequent patients. Treatment continues until disease progression, unacceptable toxicity, or patient withdrawal. After six months, patients with stable disease or better transition to a maintenance phase with 5FU and fruquintinib alone. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female ≥18 years of age.
- Written informed consent is required before performing any trial-specific tests or procedures. Signing of the informed consent form can occur outside the 28-day screening period.
- Histopathologically or cytologically confirmed locally advanced unresectable or metastatic colorectal cancer. The study will include an all-comer population, meaning that patients will not be excluded based on specific molecular markers such as microsatellite instability-high (MSI-H) or B-Raf proto-oncogene mutations (BRAF mutations). However, as part of the Standard of Care, comprehensive molecular testing will be performed to assess MSI status, and other relevant biomarkers. For patients with MSI-H or BRAF mutations confirmed, treatment may be adjusted per Standard of Care practices.
- Measurable disease per RECISTv1.1.
- No prior systemic treatment. Patients with resected disease who later develop unresectable recurrence without prior systemic therapy remain eligible.
Key exclusion criteria (39 listed)
- Hematology laboratory values of:
- Hepatic laboratory values of aspartate transaminase (AST) or alanine aminotransferase (ALT):
- Serum albumin <2.8 g/dL.
- Total bilirubin >1.7 mg/dL × ULN.
- Prothrombin time (PT) or international normalized ratio (INR) >1.5 × ULN. Note: Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible if PT and INR are within the acceptable institutional therapeutic limits.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fruquintinib Combined With ChemotherapyAlso: FruquintinibThe intervention in this trial involves administering a combination of 5FU-based chemotherapy and fruquintinib to patients with locally advanced unresectable or metastatic colorectal cancer. Patients receive either the FOLFIRI or mFOLFOX6 regimen, both of which include 5-fluorouracil (5FU), leucovorin (LV), and either irinotecan (FOLFIRI) or oxaliplatin (mFOLFOX6). Fruquintinib is given orally once daily for 21 days in each 28-day cycle. The initial dose of fruquintinib is 4 mg daily for the first three patients to assess safety; if no dose-limiting toxicities are observed, the dose is increased to 5 mg daily for subsequent participants. Treatment continues until disease progression, unacceptable toxicity, or patient withdrawal. After six months, patients with stable disease or better transition to a maintenance phase with 5FU and fruquintinib alone. | Drug | 5FU-based chemotherapy (FOLFIRI or mFOLFOX6) with fruquintinib |
Primary outcome
Time to Progression of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients
Time frame: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 24 months.
To assess the time to progression (TTP) of patients with locally advanced unresectable or metastatic colorectal cancer (mCRC) treated with 5-Fluorouracil (5FU)-based therapy in combination with fruquintinib, according to RECIST v1.1 criteria.
2 secondary outcomes
Incidence of toxicity of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients
Time frame: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws from the study, whichever came first, assessed up to 13 months.
Duration of the response of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients
Time frame: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 24 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
- Background: PubMed 33922197Sawicki T, Ruszkowska M, Danielewicz A, Niedzwiedzka E, Arlukowicz T, Przybylowicz KE. A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers (Basel). 2021 Apr 22;13(9):2025. doi: 10.3390/cancers13092025.
- Background: PubMed 33591350Biller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021 Feb 16;325(7):669-685. doi: 10.1001/jama.2021.0106.
- Background: PubMed 12360282Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002 Oct;2(10):795-803. doi: 10.1038/nrc909.
- Background: PubMed 21170960Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schutz G, Thierauch KH, Zopf D. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 2011 Jul 1;129(1):245-55. doi: 10.1002/ijc.25864. Epub 2011 Apr 22.
- Background: PubMed 12727920Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003 May;111(9):1287-95. doi: 10.1172/JCI17929.
- Background: PubMed 12181402Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter EJ, Chase A, Chessells JM, Colombat M, Dearden CE, Dimitrijevic S, Mahon FX, Marin D, Nikolova Z, Olavarria E, Silberman S, Schultheis B, Cross NC, Goldman JM. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med. 2002 Aug 15;347(7):481-7. doi: 10.1056/NEJMoa020150.
- Background: PubMed 29946728Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, Yang L, Deng Y, Chen ZD, Zhong H, Pan H, Guo W, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Chen D, Li W, Sun S, Yu Z, Cao P, Chen H, Wang J, Wang S, Wang H, Fan S, Hua Y, Su W. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018 Jun 26;319(24):2486-2496. doi: 10.1001/jama.2018.7855.
- Background: PubMed 37331369Dasari A, Lonardi S, Garcia-Carbonero R, Elez E, Yoshino T, Sobrero A, Yao J, Garcia-Alfonso P, Kocsis J, Cubillo Gracian A, Sartore-Bianchi A, Satoh T, Randrian V, Tomasek J, Chong G, Paulson AS, Masuishi T, Jones J, Csoszi T, Cremolini C, Ghiringhelli F, Shergill A, Hochster HS, Krauss J, Bassam A, Ducreux M, Elme A, Faugeras L, Kasper S, Van Cutsem E, Arnold D, Nanda S, Yang Z, Schelman WR, Kania M, Tabernero J, Eng C; FRESCO-2 Study Investigators. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. 2023 Jul 1;402(10395):41-53. doi: 10.1016/S0140-6736(23)00772-9. Epub 2023 Jun 15.
- Background: PubMed 25132748Mohelnikova-Duchonova B, Melichar B, Soucek P. FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy. World J Gastroenterol. 2014 Aug 14;20(30):10316-30. doi: 10.3748/wjg.v20.i30.10316.
- Background: PubMed 23530572Ishiguro M, Kotake K, Nishimura G, Tomita N, Ichikawa W, Takahashi K, Watanabe T, Furuhata T, Kondo K, Mori M, Kakeji Y, Kanazawa A, Kobayashi M, Okajima M, Hyodo I, Miyakoda K, Sugihara K. Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer. BMC Cancer. 2013 Mar 25;13:149. doi: 10.1186/1471-2407-13-149.
- Background: PubMed 33312889Reddy TP, Khan U, Burns EA, Abdelrahim M. Chemotherapy rechallenge in metastatic colon cancer: A case report and literature review. World J Clin Oncol. 2020 Nov 24;11(11):959-967. doi: 10.5306/wjco.v11.i11.959.
- Background: PubMed 34015686Glimelius B, Stintzing S, Marshall J, Yoshino T, de Gramont A. Metastatic colorectal cancer: Advances in the folate-fluoropyrimidine chemotherapy backbone. Cancer Treat Rev. 2021 Jul;98:102218. doi: 10.1016/j.ctrv.2021.102218. Epub 2021 May 4.
- Individual participant dataSharing planned: Yes. The Clinical Study Report will include analysis of de-identified data and will be shared with the supporter and published when available.
Related trials for Metastatic Colorectal Cancer (CRC)
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 1
A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Metastatic Colorectal Cancer
Not yet recruitingPhase 2
SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
Not yet recruitingPhase 1/2
A Phase Ib/II Study of GFH276 in Combination With Chemotherapy (± Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer
CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Maen Abdelrahim, MD, PhD, Pharm D principal investigator
The Methodist Hospital Research Institute
Abdullah Esmail, MD study director
Houston Methodist Neal Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fruquintinib Combined With Chemotherapy in people with Metastatic Colorectal Cancer (CRC), run by The Methodist Hospital Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Safiya Joseph (3462382420, sdjoseph@houstonmethodist.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Progression of 5FU in combination with fruquintinib in first-line metastatic colorectal cancer patients (time frame: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 24 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07042685, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.