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Colorectal CancerPhase 2NCT03813641

RALOX or CAPOX + Bevacizumab in the First-line Treatment of Advanced CRC(ROCB Study)

A Phase 2 study testing Raltitrexed and Capecitabine in people with Colorectal Cancer, run by Shenzhen People's Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

Raltitrexed is an inhibitor of thymidylate synthase.As a folate antimetabolite drug, raltitrexed has been used in treatment of colorectal cancer(CRC) since 1998, and also used in malignant mesothelioma.Several phase III studies performed in patients with advanced CRC showed that it is as effective as… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Colorectal Cancer
What is being tested?
Raltitrexed and Capecitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteChina
Study dates
28 Jan 2019to 31 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18~75 years;
  • Patients are diagnosed by histopathological and/or cytological examination as local advanced or metastatic colorectal cancer who are unable to undergo radical surgery with no symptom of the primary lesions；
  • There are one or more measurable lesions, the longest diameter of which is at least 10 mm by spiral CT scanning (RECIST standard, version 1.1)
  • ECOG performance status (ECOG PS) 0~1;
  • Life expectancy not less than 3 month
  • Blood routine, liver and kidney function reached the following criteria within 14 days before screening:
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  • Absolute neutrophil count (> 1.5x109/L); hemoglobin (> 9.0 g/dl); platelet count (> 100 x109/L); total bilirubin (< 1.5 times the normal upper limit (ULN); alanine aminotransferase and glutamic oxaloacetate aminotransferase (< 2.5 x ULN) in patients with liver metastasis (< 5 x ULN); alkaline phosphatase （< 3 x ULN（ in patients with liver metastasis < 5 x ULN)）; serum creatinine （< 1.5 x ULN）;
  • Adequate blood coagulation function [International Normalized Ratio (INR) ≤1.5 and Partial Thromboplastin Time (PTT) or activated PTT (aPTT) ≤1.5 x upper limit of normal (ULN)). Participants on full-dose anticoagulation must be in a stable phase of anticoagulant therapy and if taking oral anticoagulation, participants must have an INR ≤3 without clinically significant active bleeding or a high risk of bleeding.
  • Agree to provide histological specimens from previous operations for biomarker assessment and specimens remain。
  • Signed informed consent to be provided

Who cannot join

  • Previous treatment with Raltitrexed；
  • With a large amount of pleural effusions or ascites requiring puncture drainage；
  • Active clinical severe infections include hepatitis；
  • One of the following complications: 1) Gastrointestinal obstruction (including paralytic ileus) or gastrointestinal bleeding 2) Symptomatic cardiac disease (including unstable angina, myocardial infarction, and heart failure) 3) Pulmonary fibrosis or interstitial pneumonia 4) Uncontrolled diabetes mellitus 5) Uncontrolled diarrhea (that affects daily activities although adequate therapy )
  • Symptomatic brain or meningeal metastasis (unless the patient has been treated for > 6 months, the imaging results are negative in the 4 weeks before entering the study, and the clinical symptoms associated with the tumor are stable at the time of entering the study);
  • Undergoing kidney dialysis；
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  • History of other malignant tumors within 5 years, except for cured cervical carcinoma in situ or basal cell carcinoma of the skin;
  • Drug abuse and medical, psychological or social conditions may interfere with patients' participation in the study or have an impact on the evaluation of the study results；
  • Pregnant or lactating females, and males and females reluctant to use contraception
  • History of concurrent gastrointestinal perforation or gastrointestinal perforation within 1 year prior to enrollment
  • Pulmonary hemorrhage/hemoptysis ≥ Grade 2 (identified as bright red blood of not less 2.5mL) within 1 month before enrollment.
  • History of thoracotomy,laparotomy, or intestinal resection within 28 days prior to enrollment;
  • Unhealed wound (other than suture wounds due to implantation of a central venous port), traumatic fracture, or gastrointestinal ulcer
  • Current cerebrovascular disease or thromboembolism or either within 1 year before enrollment
  • Current anticoagulation therapy or requiring anticoagulation agents (> 325 mg/day of aspirin)
  • Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment)
  • Uncontrolled hypertension
  • Urine dipstick for proteinuria >+2
  • Researchers think those should be excluded

Trial locations and contacts

1 site in 1 country.

Ruilian Xu, MD contact

+8675522942497

xuruilian@126.com

Wan He, MD,phD contact

+8675522942411

hewanshenzhen@hotmail.com

China1 site, 1 recruiting

  • Shenzhen People's Hospital

    Shenzhen, Guangdong

    Ruilian Xu, MD, +8675522942497, xuruilian@126.com

    Wan He, MD,PhD, +8675522942449, hewanshenzhen@hotmail.com

    Recruiting

Other trials in China

About this study

Official title: Phase Ⅱ Clinical Study of RALOX or CAPOX Combined With Bevacizumab in the First-line Treatment of Advanced Colorectal Cancer

Raltitrexed is an inhibitor of thymidylate synthase.As a folate antimetabolite drug, raltitrexed has been used in treatment of colorectal cancer(CRC) since 1998, and also used in malignant mesothelioma.Several phase III studies performed in patients with advanced CRC showed that it is as effective as 5-fluorouracil(5-FU) /leucovorin(LV) with regard to response rates and survival. The combination of raltitrexed with oxaliplatin shows response rates of 41%-54% and median survivals of 14.6-14.8 months, which are comparable to those achieved with 5-FU/LV combination with oxaliplatin. This study discussed the efficacy and safety of raltitrexed-oxaliplatin(RALOX) combined with bevacizumab or capecitabine-oxaliplatin(CAPOX) combined with bevacizumab in first-line treatment of patients with advanced colorectal cancer who could not undergo radical surgery. The main endpoint will be progression free survival (PFS). The secondary endpoints will be overall survival, objective response rate and disease control rate (OS,ORR and DCR).It is expected that raltitrexed may be one of options for the treatment of advanced CRC in the first-line setting.

Read the detailed description

According to the inclusion and exclusion criteria, the patients will be randomly divided into two groups: the experimental group (group A) will be administered with raltitrexed 3mg/m2 intravenously combined with oxaliplatin and bevacizumab, repeated every 21 days. The control group (group B) will be administered with orally capecitabine (1000mg/m2, d 1-14) combined with oxaliplatin and bevacizumab, repeated every 21 days. After 8 cycles of treatments, if evaluated as complete response(CR),partial response(PR) or stable disease(SD), CRC patients will go into maintenance therapy wtih raltitrexed combined with bevacizumab in group A or capecitabine combined with bevacizumab in group B respectively, ended in disease progression(PD) , symptoms deterioration, unacceptable toxicity, death or withdrawal of consent (whichever occurs first). The radiological efficacy will be evaluated every 6 weeks (2 treatment cycles) and non-PD (PD criteria referring to RECIST 1.1 criteria) patients will continue to be treated until the cancer progression or the patient's intolerable toxicity or death. Toxic side effects and quality of life will be assessed at the same time.

Follow up participants and analyse primary endpoint (PFS) and secondary endpoints (OS,ORR and DCR).The causes of confirmed missing data in the trial should be recorded in detail to determine the mechanism of missing data and choose the suitable missing data handling methods.

Being tested
Raltitrexed, Capecitabine
Keywords
Raltitrexed, First-line therapy, Bevacizumab, Colorectal Cancer
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RaltitrexedDrug

    Also called Tomudex

    Experimental: Oxaliplatin + Raltitrexed + Bevacizumab The above schemes are repeated every three weeks. After 8 cycles, such as CR, PR or SD, the regimen is changed to Raltitrexed (3mg/m2, intravenous drip for 15 minutes, d1)+bevacizumab (7.5mg/kg, intravenous drip, d1). The regimen is repeated every 3 weeks until the disease progresses.

  • CapecitabineDrug

    Also called Xeloda

    Other: Oxaliplatin + Capecitabine + Bevacizumab The above schemes are repeated every three weeks. After 8 cycles, such as CR, PR or SD, the regimen is changed to Capecitabine (1000mg/m2 po. d1-14)+bevacizumab (7.5mg/kg, intravenous drip, d1). The regimen is repeated every 3 weeks until the disease progresses.

Study groups in NCT03813641
Study groupRoleWhat they receive
RALOX + bevacizumabExperimentalOxaliplatin 130mg/m2, i.v.gtt 2h, d1 Raltitrexed 3mg/m2, i.v.gtt 15min ,d1 Bevacizumab 7.5mg/kg, i.v.gtt, d1 The above schemes are repeated every three weeks. After 8 cycles, such as CR, PR or SD, the regimen is changed to raltitrexed (3mg/m2, intravenous drip for 15 minutes, d1)+bevacizumab (7.5mg/kg, intravenous drip, d1). The regimen is repeated every 3 weeks until the disease progresses.
Receives: Drug: Raltitrexed
CAPOX + bevacizumabActive comparatorOxaliplatin 130mg/m2, i.v.gtt 2h, d1 Capecitabine 1000mg/m2, po. ,d1 Bevacizumab 7.5mg/kg, i.v.gtt, d1 The above schemes are repeated every three weeks. After 8 cycles, such as CR, PR or SD, the regimen is changed to Capecitabine (1000mg/m2 po. d1-14)+bevacizumab (7.5mg/kg, intravenous drip, d1). The regimen is repeated every 3 weeks until the disease progresses.
Receives: Drug: Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) Time

    PFS is defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) [according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1] or death due to any cause, whichever will be first. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Participants who died without a reported prior progression will be considered to have progressed on the day of their death. Participants who do not progress or be lost to follow-up will be censored at the day of their last radiographic tumor assessment.

    Measured: The follow-up period ranges from the first patient recruited to the last patient within 6 months after admission, up to 2 years.

Secondary outcomes (3)

  1. Overall Survival (OS)

    OS is defined as the time in months from the date of randomization to the date of death from any cause. For participants not known to have died as of the cut-off date, OS will be censored at the last known date alive.

    Measured: The follow-up period ranges from the first patient recruited to the last patient within 6 months after admission,up to 2 years.

  2. Percentage of Participants Achieving an Objective Response (Objective Response Rate)

    The objective response rate is equal to the proportion of participants achieving a best overall response of partial response or complete response (PR + CR). Response is defined using RECIST, v. 1.1 criteria. CR is defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions; PR is defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameter.

    Measured: The follow-up period ranges from the first patient recruited to the last patient within 3 months after admission.

  3. Percentage of Participants Achieving a Stable Disease (SD) or a confirmed CR or PR (Disease Control Rate)

    Participants achieved disease control if they have a best overall response of CR, PR or SD. According to RECIST v1.1, CR is the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all non-target lesions, and the normalization of tumor marker levels (if tumor markers were initially above the ULN); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started.

    Measured: The follow-up period ranges from the first patient recruited to the last patient within 3 months after admission.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2019
  2. Study start28 Jan 2019
  3. Primary completion28 Feb 2021 (estimated)
  4. Study completion31 Dec 2021 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Model description
Randomized controlled trial
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03813641
Sponsor's protocol ID
Shenzhen CRC-002
Status last verified
Sep 2019
First submitted
20 Jan 2019
Last updated
9 Sep 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kindler HL, Shulman KL. Metastatic colorectal cancer. Curr Treat Options Oncol. 2001 Dec;2(6):459-71. doi: 10.1007/s11864-001-0068-7.

    PubMed 12057092

  • Meta-analysis Group In Cancer; Piedbois P, Rougier P, Buyse M, Pignon J, Ryan L, Hansen R, Zee B, Weinerman B, Pater J, Leichman C, Macdonald J, Benedetti J, Lokich J, Fryer J, Brufman G, Isacson R, Laplanche A, Levy E. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol. 1998 Jan;16(1):301-8. doi: 10.1200/JCO.1998.16.1.301.

    PubMed 9440757

  • Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-Analysis Project. J Clin Oncol. 1992 Jun;10(6):896-903. doi: 10.1200/JCO.1992.10.6.896.

    PubMed 1534121

  • Meta-Analysis Group In Cancer; Levy E, Piedbois P, Buyse M, Pignon JP, Rougier P, Ryan L, Hansen R, Zee B, Weinerman B, Pater J, Leichman C, Macdonald J, Benedetti J, Lokich J, Fryer J, Brufman G, Isacson R, Laplanche A, Quinaux E, Thirion P. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol. 1998 Nov;16(11):3537-41. doi: 10.1200/JCO.1998.16.11.3537.

    PubMed 9817272

  • Becker K, Erckenbrecht JF, Haussinger D, Frieling T. Cardiotoxicity of the antiproliferative compound fluorouracil. Drugs. 1999 Apr;57(4):475-84. doi: 10.2165/00003495-199957040-00003.

    PubMed 10235688

  • Wacker A, Lersch C, Scherpinski U, Reindl L, Seyfarth M. High incidence of angina pectoris in patients treated with 5-fluorouracil. A planned surveillance study with 102 patients. Oncology. 2003;65(2):108-12. doi: 10.1159/000072334.

    PubMed 12931015

  • Rougier P, Van Cutsem E, Bajetta E, Niederle N, Possinger K, Labianca R, Navarro M, Morant R, Bleiberg H, Wils J, Awad L, Herait P, Jacques C. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet. 1998 Oct 31;352(9138):1407-12. doi: 10.1016/S0140-6736(98)03085-2.

    PubMed 9807986

  • Cunningham D, Pyrhonen S, James RD, Punt CJ, Hickish TF, Heikkila R, Johannesen TB, Starkhammar H, Topham CA, Awad L, Jacques C, Herait P. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet. 1998 Oct 31;352(9138):1413-8. doi: 10.1016/S0140-6736(98)02309-5.

    PubMed 9807987

  • Seymour MT, Maughan TS, Ledermann JA, Topham C, James R, Gwyther SJ, Smith DB, Shepherd S, Maraveyas A, Ferry DR, Meade AM, Thompson L, Griffiths GO, Parmar MK, Stephens RJ; FOCUS Trial Investigators; National Cancer Research Institute Colorectal Clinical Studies Group. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007 Jul 14;370(9582):143-152. doi: 10.1016/S0140-6736(07)61087-3.

    PubMed 17630037

  • Graeven U, Arnold D, Reinacher-Schick A, Heuer T, Nusch A, Porschen R, Schmiegel W. A randomised phase II study of irinotecan in combination with 5-FU/FA compared with irinotecan alone as second-line treatment of patients with metastatic colorectal carcinoma. Onkologie. 2007 Apr;30(4):169-74. doi: 10.1159/000099636. Epub 2007 Mar 23.

    PubMed 17396039

  • Leonard P, Seymour MT, James R, Hochhauser D, Ledermann JA. Phase II study of irinotecan with bolus and high dose infusional 5-FU and folinic acid (modified de Gramont) for first or second line treatment of advanced or metastatic colorectal cancer. Br J Cancer. 2002 Nov 18;87(11):1216-20. doi: 10.1038/sj.bjc.6600641.

    PubMed 12439708

  • Rougier P, Lepille D, Bennouna J, Marre A, Ducreux M, Mignot L, Hua A, Mery-Mignard D. Antitumour activity of three second-line treatment combinations in patients with metastatic colorectal cancer after optimal 5-FU regimen failure: a randomised, multicentre phase II study. Ann Oncol. 2002 Oct;13(10):1558-67. doi: 10.1093/annonc/mdf259.

    PubMed 12377643

  • Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, Andre T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. doi: 10.1200/JCO.2009.27.6055. Epub 2010 Oct 4.

    PubMed 20921462

  • Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, Schulz J, Richards D, Soufi-Mahjoubi R, Wang B, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007 Oct 20;25(30):4779-86. doi: 10.1200/JCO.2007.11.3357.

    PubMed 17947725

  • Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004 Jan 15;22(2):229-37. doi: 10.1200/JCO.2004.05.113. Epub 2003 Dec 2.

    PubMed 14657227

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Raltitrexed and Capecitabine in people with Colorectal Cancer, run by Shenzhen People's Hospital at 1 site in China.

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 10 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 9 Sep 2019. 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 China. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ruilian Xu, MD (+8675522942497, xuruilian@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) Time (time frame: The follow-up period ranges from the first patient recruited to the last patient within 6 months after admission, up to 2 years.). 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 NCT03813641, which also lists 34 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 Sep 2019.

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