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Colorectal NeoplasmsPhase 2PREVIUMNCT02175654

Regorafenib as Single Agent in Patients With Metastatic Colorectal Cancer (mCRC) With Any RAS or BRAF Mutation Previously Treated With FOLFOXIRI Plus Bevacizumab

A Phase 2 study testing Regorafenib in people with Colorectal Neoplasms and Metastatic Disease, run by Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) at 1 site in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to assess the efficacy of single-agent regorafenib in the second-line treatment in metastatic colorectal cancer with any RAS or BRAF mutation previously treated with FOLFOXIRI plus bevacizumab in terms of progression-free survival at 6 months. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Neoplasms, Metastatic Disease
What is being tested?
Regorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteSpain
Study dates
Jun 2014to Feb 2016
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signing of the informed consent form.
  • The patient must be able to understand the information and state expressly his or her desire to take part in the study.
  • Age ≥ 18 years.
  • Histologically or cytologically documented adenocarcinoma of the colon or rectum.
  • Patients with metastatic colorectal cancer (stage IV) with any RAS or BRAF mutation.
  • To have received first_line treatment with bevacizumab in combination with chemotherapy with the three drugs 5FU/leucovorin (LV), irinotecan and oxaliplatin (FOLFOXIRI), and
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  • have had radiological progression of the disease during the first_line treatment, or
  • have had radiological progression of the disease within a period of ≤ 6 months after the last dose of first-line treatment, or
  • have discontinued part or all of the first_line treatment due to toxicity and have had radiological progression of the disease within a period of ≤ 6 months after the last dose of first-line treatment.
  • The patient will have to have received at least one cycle of bevacizumab in combination with FOLFOXIRI + bevacizumab as part of the firstline treatment.
  • Patients may have received fluoropyrimidinebased adjuvant treatment with or without oxaliplatin.
  • Existence of at least one measurable unidimensional lesion using CT or MRI based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1
  • Overall Eastern Cooperative Oncology Group (ECOG) performance ≤1.
  • Patient's commitment to compliance with the oral medication throughout the duration of the study
  • Life expectancy of at least 3 months
  • Adequate bone marrow, renal and hepatic function, defined as:
  • Neutrophils ≥ 1500/mm3
  • Platelets ≥100,000/mm3
  • Haemoglobin ≥ 9,0 g/dL
  • Serum Creatinine ≤ 1.5 x LSN
  • Bilirubin levels ≤ 1.5 x LSN
  • AST and ALT levels ≤ 2.5 x ULN (if liver metastases < 5 x ULN)

Who cannot join

  • Prior treatment with regorafenib.
  • Assignment prior to treatment during this study. Patients who are permanently withdrawn from participation in the study treatment will not be allowed to return to it.
  • Prior or concurrent presence of another neoplastic disease that is different in terms of tumour site and histology of the colorectal cancer in the 5 years prior to the inclusion of the patient in the study, except in situ cervical cancer, superficial bladder carcinoma [Ta (non-invasive), Tis (carcinoma in situ) and T1 (tumour invades lamina propria)] and non-melanoma skin tumours.
  • Presence or history of brain metastases or meningeal tumours.
  • Major surgery, open biopsy or traumatic injury within 28 days prior to the start of patient treatment with the study medication.
  • Extended-field radiotherapy within 4 weeks prior to inclusion or limited-field radiotherapy in the previous 2 weeks. Patients must have recovered from all treatment-related toxicities.
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  • Pregnant or breastfeeding women. Women of childbearing age must use adequate contraception. Women of childbearing age must have a negative pregnancy test within 7 days prior to starting with the study medication.
  • Women of childbearing age and men who wish to take part in the study must agree to use adequate contraception from the signing of the informed consent until at least 3 months after stopping the study medication. The investigator or the person designated by him or her will ensure and advise as to the contraceptive methods that should be used.
  • Appropriate contraceptive methods include abstinence, oral contraceptives, transdermal patches and injections of sustained-release progestin (starting at least 4 weeks before administration of the IMP), double-barrier method: condom or female condom (diaphragm or cervical/vaginal condom) plus spermicide, intrauterine device (IUD), intrauterine system, implant or vaginal ring (in place at least 4 weeks before administration of the IMP) or male partner sterilisation (vasectomy with documentation of azoospermia) prior to inclusion of the woman in the trial if he is the woman's only sexual partner.
  • Active congestive heart failure class 2 or higher on the New York Heart Association (NYHA) scale.
  • Unstable angina (angina symptoms at rest), new_onset angina (having appeared in the past 3 months) or acute myocardial infarction that has occurred in the 6 months prior to starting with the study medication.
  • Cardiac arrhythmias that require anti-arrhythmic therapy (only beta blockers and digoxin would be allowed as concomitant medication for these patients).
  • Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg) despite proper medical management.
  • Patients with phaeochromocytoma.
  • Pleural effusion or ascites that cause breathing difficulties (dyspnoea of grade ≥ 2 of the CTC).
  • Venous or arterial thromboembolism or embolic events such as cerebrovascular accidents (including transient ischaemic attacks), deep vein thrombosis or pulmonary thromboembolism that have occurred in the 6 months prior to starting with the study medication.
  • Active infection > grade 2 based on the NCI CTC, v. 4.0.
  • Human immunodeficiency virus (HIV) infection.
  • Active hepatitis B or C, or hepatitis B or C infection that requires treatment with antiviral drugs.
  • Patients with mental disorders that require medication.
  • History of organ transplants.
  • Patients with evidence or history of bleeding diathesis. Any bleeding or bleeding event > Common Toxicity Criteria for Adverse Effects (CTCAE) grade 3 in the 4 weeks prior to starting with the study medication.
  • Presence of unhealed wounds, ulcers or bone fractures.
  • Kidney failure requiring haemodialysis or peritoneal dialysis.
  • Dehydration based on NCI CTC criteria, version 4, of > 1.
  • Substance abuse or a history of medical, social or psychological conditions that may interfere with study participation or compliance with the efficacy and safety assessments planned in the study.
  • Known hypersensitivity to regorafenib or any of its excipients.
  • Presence of any disease or medical condition that might interfere with patient safety or may compromise treatment compliance with it.
  • Interstitial lung disease with signs and symptoms present at the time of signing the informed consent.
  • Patients who are unable to swallow oral medication.
  • Persistent proteinuria > grade 3 based on the NCI CTC, version 4.0 (> 3.5 g/24 hours).
  • Intestinal malabsorption syndrome.
  • Close personal relationship with the research staff, such as family members of the investigator or dependents (e.g. employees or students of the research centre).
  • Unresolved toxicity grade > 1 based on the NCI CTC, version 4.0 (except alopecia), related to any previous therapy or procedure.

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Spanish Cooperative Group for Digestive Tumour Therapy (TTD)

    Madrid, 28046

Other trials in Spain

About this study

Official title: Phase II Study of Regorafenib as Single Agent for the Treatment of Patients With Metastatic Colorectal Cancer (mCRC) With Any RAS or BRAF Mutation Previously Treated With FOLFOXIRI Plus Bevacizumab

The purpose of this study is to assess the efficacy of single-agent regorafenib in the second-line treatment in metastatic colorectal cancer with any RAS or BRAF mutation previously treated with FOLFOXIRI plus bevacizumab in terms of progression-free survival at 6 months.

Being tested
Regorafenib
Keywords
metastatic colorectal cancer, RAS/BRAF mutation, Regorafenib, FOLFOXIRI, Bevacizumab
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.

Study groups in NCT02175654
Study groupRoleWhat they receive
RegorafenibExperimentalRegorafenib will be administered orally at the initial dosage of 160 mg per day for 3 weeks, followed by one week of rest, according to the 3/1 regimen
Receives: Drug: Regorafenib

What is being measured

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

  1. Progression free survival rate at 6 months

    Measured: 6 months

Secondary outcomes (16)

  1. Objective response rate based on the Response Evaluation Criteria in Solid Tumors criteria

    Measured: 36 months

  2. Disease control rate

    Measured: 36 months

  3. Response according other criteria (Appendix 9)

    Measured: 36 months

  4. Time to response

    Measured: 36 months

  5. Progression free survival

    Measured: 36 months

  6. Time to treatment failure

    Measured: 36 months

  7. Response duration

    Measured: 36 months

  8. Duration of stable disease

    Measured: 36 months

  9. Overall survival

    Measured: 36 months

  10. Time to progression

    Measured: 36 months

  11. Incidence and severity of adverse events (AE) (NCI CTC, version 3.0)

    Measured: 36 months

  12. Changes in laboratory values

    hemoglobin, hematocrit, platelets, creatinine, total bilirubin, alkaline phosphatase, ALT, AST, BUN or urea, glucose, sodium, potassium, calcium, phosphorus, LDH, GGT, magnesium, albumin, total protein, uric acid and lipase.

    Measured: baseline and end of treatment, an expected average of 4 months

  13. Change in vital signs (weight loss and hypertension)

    Measured: baseline and end of treatment, an expected average of 4 months

  14. Incidence of dose adjustments and compliance

    Measured: 36 months

  15. Incidence of concomitant medication

    Measured: 36 months

  16. Changes in ECOG performance status over time from baseline

    Measured: baseline and end of treatment, an expected average of 4 months

Timeline

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

  1. First posted26 Jun 2014 (estimated)
  2. Study startJun 2014
  3. Primary completionFeb 2016
  4. Study completionFeb 2016

Why it stopped: The trial was prematurely closed due to lack of accrual

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02175654
Sponsor's protocol ID
TTD-14-01
Other IDs
2014-000703-26, 2014
Acronym
PREVIUM
Status last verified
Jul 2017
First submitted
12 Jun 2014
Last updated
1 Aug 2017
Results posted
No
Data monitoring committee
No

Publications

  • Garcia-Alfonso P, Benavides M, Falco E, Munoz A, Gomez A, Sastre J, Rivera F, Montagut C, Salgado M, Lopez-Ladron A, Lopez R, Ruiz de Mena I, Duran G, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD). Single-Agent Regorafenib in Metastatic Colorectal Cancer Patients with Any RAS or BRAF Mutation Previously Treated with FOLFOXIRI plus Bevacizumab (PREVIUM Trial). Oncologist. 2018 Nov;23(11):1271-e128. doi: 10.1634/theoncologist.2018-0316. Epub 2018 Aug 17.

    PubMed 30120161

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib in people with Colorectal Neoplasms and Metastatic Disease, run by Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) at 1 site in Spain.

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 22 inclusion and 34 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: stopped early, as of the sponsor's last update on 1 Aug 2017. 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 Spain. 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?

The study was stopped early (reason given: The trial was prematurely closed due to lack of accrual). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival rate at 6 months (time frame: 6 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 NCT02175654, which also lists 1 linked publication.

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 1 Aug 2017.

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