Colorectal CancerPhase 2PARERENCT04787341
PAnitumumab REchallenge Followed by REgorafenib Versus the Reverse Sequence
A Phase 2 study testing Regorafenib and Panitumumab in people with Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 1 site in Italy.
Trial summary
The association of doublet chemotherapy (FOLFOX and FOLFIRI) and anti-EGFR-moAbs (panitumumab or cetuximab) is a standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC patients, especially with left-sided primary tumour. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Regorafenib and Panitumumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 213 participants
- Where
- 1 siteItaly
- Study dates
- 15 Dec 2020to 28 May 2026
- 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
- Age ≥ 18 years.
- Written informed consent to molecular analyses.
- Histologically proven diagnosis of CRC.
- At least one measurable lesion according to RECIST1.1
- ECOG PS ≤ 1.
- mCRC previously treated for metastatic disease with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and anti-angiogenic monoclonal antibody (bevacizumab or aflibercept).
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- RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E mutation) wt status of primary CRC or related metastasis (local laboratory assessment).
- Previous first-line anti-EGFR-containing therapy producing at least a partial response or a stable disease ≥ 6 months.
- At least 4 months elapsed between the end of first-line anti-EGFR administration and screening.
- At least one line of therapy between the end of first-line anti-EGFR administration and screening.
- Availability of plasma sample for liquid biopsy within 28 days prior enrolment.
- RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E mutation) wt status of ct-DNA at screening (central laboratory assessment by means of IdyllaTM ctKRAS-NRAS-BRAF Mutation Test).
- Written informed consent to study treatment and procedures.
- Life expectancy of at least 12 weeks.
- Availability of archival tumour tissue (primary tumour and metastases or at least one of the two) for biomarker analysis.
- Availability of biological samples for translational molecular analyses.
- Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl.
- Total bilirubin ≤ 1.5 fold the upper-normal limits (UNL), ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in the case of liver metastases), alkaline phosphatase ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases).
- Creatinine clearance ≥ 50 mL/min or serum creatinine ≤1.5 x UNL.
- Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
- Subjects and their partners must be willing to avoid pregnancy during the trial and until 8 weeks after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception).
- Will and ability to comply with the protocol.
Who cannot join
- Previous treatment with regorafenib.
- Radiotherapy to any site within 4 weeks before the study.
- Untreated brain metastases or spinal cord compression or primary brain tumours.
- Evidence of bleeding diathesis or coagulopathy.
- Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
- Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
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- Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment.
- Any previous venous thromboembolism ≥ NCI CTCAE Grade 4.
- History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
- Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ.
- Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
- Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.
- Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.
- Diagnosis of interstitial pneumonitis or pulmonary fibrosis.
- Active uncontrolled infections or other clinically relevant concomitant illness contraindicating administration of panitumumab and regorafenib.
- Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer).
- Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 8 weeks after the last trial treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase II Study of Panitumumab Rechallenge Followed by Regorafenib Versus the Reverse Sequence in RAS and BRAF Wild-type Chemorefractory Mestastatic Colorectal Cancer Patients
The association of doublet chemotherapy (FOLFOX and FOLFIRI) and anti-EGFR-moAbs (panitumumab or cetuximab) is a standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC patients, especially with left-sided primary tumour.
In RAS wt mCRC patients refractory to chemotherapy and anti-EGFR naive, the standard treatment sequence is an anti-EGFR-based therapy (panitumumab or cetuximab +/- irinotecan) followed by regorafenib.
Read more
In a phase II randomized Japanese study named REVERCE, a higher OS was reported in favour of an experimental strategy of regorafenib followed at progression by cetuximab +/- irinotecan compared with the reverse standard sequence in chemorefractory and anti-EGFR-naïve, RAS wt mCRC patients.
However, the limitations of the REVERCE study (phase II trial with a premature conclusion for poor accrual) do not allow us to draw definitive conclusions. In addition, nowadays, patients candidates to an anti-EGFR-based treatment, receive anti-EGFRMoAbs in earlier lines of therapy thus affecting the translation of these results in the current clinical practice.
Retrospective analyses and a phase II single-arm trial showed promising activity of anti-EGFR rechallenge in patients who previously achieved benefit from a first-line anti- EGFR-based treatment and not bearing RAS mutation on ct-DNA at the rechallenge baseline.
Based on these considerations, the Investigators designed the present phase II randomized study of panitumumab followed at progression by regorafenib versus the reverse sequence in RAS and BRAF wt mCRC patients with the following characteristics:
- previous treatment with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and an anti-angiogenic agent (bevacizumab or aflibercept);
- RECIST response or stable disease lasting at least 6 months to a previous first-line anti-EGFR-based treatment;
- RAS and BRAF wt ct-DNA at the time of screening. The aim of this study is to compare the two sequences in a Caucasian population of patients candidates to anti-EGFR rechallenge.
- Conditions
- Colorectal Cancer
- Being tested
- Regorafenib, Panitumumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Also called panitumumab
regorafenib administered until progression, unacceptable toxicity or patient's refusal followed after progression by panitumumab until further progression, unacceptable toxicity or patient's refusal in RAS and BRAF wt mCRC patients with the following characteristics:
- previous treatment with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and anti-angiogenic agent (bevacizumab or aflibercept);
- RECIST response or stable disease lasting at least 6 months to a previous first-line anti-EGFR-based treatment;
- RAS and BRAF wt ct-DNA at the time of screening.
PanitumumabDrug
Also called regorafenib
panitumumab administered until progression, unacceptable toxicity or patient's refusal followed after progression by regorafenib until further progression, unacceptable toxicity or patient's refusal in RAS and BRAF wt mCRC patients with the following characteristics:
- previous treatment with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and anti-angiogenic agent (bevacizumab or aflibercept);
- RECIST response or stable disease lasting at least 6 months to a previous first-line anti-EGFR-based treatment;
- RAS and BRAF wt ct-DNA at the time of screening.
| Study group | Role | What they receive |
|---|---|---|
| Panitumumab followed by Regorafenib | Active comparator | Not described Receives: Drug: Panitumumab |
| Regorafenib followed by Panitumumab | Experimental | Not described Receives: Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
time from randomization to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.
Measured: 30 months
Secondary outcomes (6)
Overall Toxicity Rate
percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during panitumumab and regorafenib
Measured: 24 months
G3/4 Toxicity Rate
the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during panitumumab and regorafenib.
Measured: 24 months
1st-Progression free survival
time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first.
Measured: 21 months
2nd-Progression free survival
the time from the beginning of the second-line study treatment to the documentation of objective disease progression according to RECIST 1.1 criteria or death due to any cause, whichever occurs first
Measured: 24 months
Time to Failure of strategy
the time from randomization till the first of any of the following events: a) death; b) disease progression according to RECIST 1.1 criteria on any treatment given after 1st progression
Measured: 24 months
Objective Response Rate
the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during panitumumab and regorafenib.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2021
- Study start15 Dec 2020
- Primary completion7 Aug 2025
- Study completion28 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 213 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gruppo Oncologico del Nord-Ovest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04787341
- Sponsor's protocol ID
- EUDRACT 2019-002834-35
- Acronym
- PARERE
- Status last verified
- Aug 2026
- First submitted
- 24 Feb 2021
- Last updated
- 28 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ciraci P, Germani MM, Pietrantonio F, Manca P, Lonardi S, Busico A, Bergamo F, Burgio V, Mannavola F, Di Donato S, Fenocchio E, Palermo F, Capone I, De Grandis MC, Pella N, Scartozzi M, Antonuzzo L, Passardi A, Claravezza M, Salvatore L, Tamberi S, Randon G, Conca E, Conca V, Antoniotti C, Moretto R, Masi G, Boni L, Rossini D, Cremolini C; GONO Foundation Investigators. Re-treatment with panitumumab followed by regorafenib versus the reverse sequence in chemorefractory metastatic colorectal cancer patients with RAS and BRAF wild-type circulating tumor DNA: the PARERE study by GONO. Ann Oncol. 2026 Jan;37(1):79-91. doi: 10.1016/j.annonc.2025.10.002. Epub 2025 Oct 18.
PubMed 41115464
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Study of Panitumumab Rechallenge Followed by Regorafenib Versus the Reverse Sequence in RAS and BRAF Wild-type Chemorefractory Mestastatic Colorectal Cancer Patients
- ClinicalTrials.gov ID
- NCT04787341
- Acronym / sponsor ID
- PARERE / EUDRACT 2019-002834-35
- Conditions
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 213 participants (actual)
- Lead sponsor
- Gruppo Oncologico del Nord-OvestUniversity, hospital or other
- Collaborators
- Bayer, Amgen
- Study start
- 15 Dec 2020 (actual)
- Primary completion
- 7 Aug 2025 (actual)
- Study completion
- 28 May 2026 (actual)
- First posted
- 8 Mar 2021 (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.
The association of doublet chemotherapy (FOLFOX and FOLFIRI) and anti-EGFR-moAbs (panitumumab or cetuximab) is a standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC patients, especially with left-sided primary tumour.
In RAS wt mCRC patients refractory to chemotherapy and anti-EGFR naive, the standard treatment sequence is an anti-EGFR-based therapy (panitumumab or cetuximab +/- irinotecan) followed by regorafenib.
In a phase II randomized Japanese study named REVERCE, a higher OS was reported in favour of an experimental strategy of regorafenib followed at progression by cetuximab +/- irinotecan compared with the reverse standard sequence in chemorefractory and anti-EGFR-naïve, RAS wt mCRC patients.
However, the limitations of the REVERCE study (phase II trial with a premature conclusion for poor accrual) do not allow us to draw definitive conclusions. In addition, nowadays, patients candidates to an anti-EGFR-based treatment, receive anti-EGFRMoAbs in earlier lines of therapy thus affecting the translation of these results in the current clinical practice.
Retrospective analyses and a phase II single-arm trial showed promising activity of anti-EGFR rechallenge in patients who previously achieved benefit from a first-line anti- EGFR-based treatment and not bearing RAS mutation on ct-DNA at the rechallenge baseline.
Based on these considerations, the Investigators designed the present phase II randomized study of panitumumab followed at progression by regorafenib versus the reverse sequence in RAS and BRAF wt mCRC patients with the following characteristics:
- previous treatment with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and an anti-angiogenic agent (bevacizumab or aflibercept);
- RECIST response or stable disease lasting at least 6 months to a previous first-line anti-EGFR-based treatment;
- RAS and BRAF wt ct-DNA at the time of screening. The aim of this study is to compare the two sequences in a Caucasian population of patients candidates to anti-EGFR rechallenge.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Panitumumab followed by Regorafenib | Active comparator | Drug: Panitumumab |
| Regorafenib followed by Panitumumab | Experimental | Drug: Regorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Age ≥ 18 years.
- Written informed consent to molecular analyses.
- Histologically proven diagnosis of CRC.
- At least one measurable lesion according to RECIST1.1
- ECOG PS ≤ 1.
Key exclusion criteria (17 listed)
- Previous treatment with regorafenib.
- Radiotherapy to any site within 4 weeks before the study.
- Untreated brain metastases or spinal cord compression or primary brain tumours.
- Evidence of bleeding diathesis or coagulopathy.
- Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
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 |
|---|---|---|
| RegorafenibAlso: panitumumabregorafenib administered until progression, unacceptable toxicity or patient's refusal followed after progression by panitumumab until further progression, unacceptable toxicity or patient's refusal in RAS and BRAF wt mCRC patients with the following characteristics: 1. previous treatment with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and anti-angiogenic agent (bevacizumab or aflibercept); 2. RECIST response or stable disease lasting at least 6 months to a previous first-line anti-EGFR-based treatment; 3. RAS and BRAF wt ct-DNA at the time of screening. | Drug | Regorafenib followed by Panitumumab |
| PanitumumabAlso: regorafenibpanitumumab administered until progression, unacceptable toxicity or patient's refusal followed after progression by regorafenib until further progression, unacceptable toxicity or patient's refusal in RAS and BRAF wt mCRC patients with the following characteristics: 1. previous treatment with, or not considered candidates for, fluoropyrimidine, oxaliplatin, irinotecan and anti-angiogenic agent (bevacizumab or aflibercept); 2. RECIST response or stable disease lasting at least 6 months to a previous first-line anti-EGFR-based treatment; 3. RAS and BRAF wt ct-DNA at the time of screening. | Drug | Panitumumab followed by Regorafenib |
Primary outcome
Overall survival
Time frame: 30 months
time from randomization to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.
6 secondary outcomes
Overall Toxicity Rate
Time frame: 24 months
G3/4 Toxicity Rate
Time frame: 24 months
1st-Progression free survival
Time frame: 21 months
2nd-Progression free survival
Time frame: 24 months
Time to Failure of strategy
Time frame: 24 months
Objective Response Rate
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
- Derived from this study: PubMed 41115464Ciraci P, Germani MM, Pietrantonio F, Manca P, Lonardi S, Busico A, Bergamo F, Burgio V, Mannavola F, Di Donato S, Fenocchio E, Palermo F, Capone I, De Grandis MC, Pella N, Scartozzi M, Antonuzzo L, Passardi A, Claravezza M, Salvatore L, Tamberi S, Randon G, Conca E, Conca V, Antoniotti C, Moretto R, Masi G, Boni L, Rossini D, Cremolini C; GONO Foundation Investigators. Re-treatment with panitumumab followed by regorafenib versus the reverse sequence in chemorefractory metastatic colorectal cancer patients with RAS and BRAF wild-type circulating tumor DNA: the PARERE study by GONO. Ann Oncol. 2026 Jan;37(1):79-91. doi: 10.1016/j.annonc.2025.10.002. Epub 2025 Oct 18.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 Regorafenib and Panitumumab in people with Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 1 site in Italy.
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 17 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: finished, as of the sponsor's last update on 28 Aug 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 Italy. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall survival (time frame: 30 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 NCT04787341, 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 28 Aug 2026.