Elderly Metastatic Colorectal Cancer PatientsPhase 2PANDANCT02904031
Study of I Line FOLFOX + Panitumumab vs 5FU + Panitumumab in RAS and BRAF WT Metastatic Colorectal Cancer Elderly Patients
A Phase 2 study testing 5-fluorouracil, oxaliplatin and l-leucovorin in people with Elderly Metastatic Colorectal Cancer Patients, run by Gruppo Oncologico del Nord-Ovest at 1 site in Italy.
Trial summary
Few data are available about the treatment of metastatic colorectal cancer (mCRC) elderly patients with anti-EGFR agents in combination with chemotherapy. Up today, most of the available data are from retrospective/post-hoc analyses, making them difficult to translate to everyday clinical practice. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Elderly Metastatic Colorectal Cancer Patients
- What is being tested?
- 5-fluorouracil, oxaliplatin and l-leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2016to Oct 2020
- 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 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Written informed consent to study procedures and to molecular analyses.
- Histologically proven diagnosis of colorectal cancer.
- Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
- At least one measurable lesion according to RECIST1.1 criteria.
- Availability of a tumoral sample (primary and/or metastatic sites).
- Age ≥ 70 years.
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- ECOG PS 1 or 2 for patients aged 70 to 75 years; ECOG PS 0 or 1 for patients aged > 75 years.
- Life expectancy of at least 12 weeks.
- Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse.
- RAS and BRAF status wild-type of primary colorectal cancer or related metastasis, centrally assessed.
- Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl.
- Total bilirubin ≤ 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in 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.
- Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception).
- Geriatric assessment by means of G8 screening tool and CRASH score.
- Will and ability to comply with the protocol.
Who cannot join
- Previous treatment for metastatic disease.
- Radiotherapy to any site within 4 weeks before the study.
- Previous adjuvant oxaliplatin-containing chemotherapy.
- Previous treatment with EGFR inhibitors.
- Untreated brain metastases or spinal cord compression or primary brain tumors.
- History or evidence upon physical examination of CNS disease unless adequately treated.
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- Symptomatic peripheral neuropathy > 1 grade NCIC-CTG criteria.
- Creatinine clearance < 50 mL/min or serum creatinine >1.5 x UNL.
- Clinical signs of malnutrition.
- Neutrophils <1.5 x 109/L, Platelets <100 x 109/L, Hgb <9 g/dl.
- Diagnosis of interstitial pneumonitis or pulmonary fibrosis.
- Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration.
- 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 (CHF), serious cardiac arrhythmia requiring medication.
- Treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer)
- 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.
- Definite contraindications for the use of corticosteroids and antihistamines as premedication.
- 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.
- Sexually active males unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase II Study of First-Line FOLFOX Plus Panitumumab Versus 5FU Plus Panitumumab in RAS And BRAF Wild-Type Metastatic Colorectal Cancer Elderly Patients
- Few data are available about the treatment of metastatic colorectal cancer (mCRC) elderly patients with anti-EGFR agents in combination with chemotherapy. Up today, most of the available data are from retrospective/post-hoc analyses, making them difficult to translate to everyday clinical practice.
- FOLFOX plus panitumumab is a standard first-line therapy option for RAS wild-type untreated mCRC patients. Slight adjustments in chemo-dosage are commonly applied in routinary practice to elderly patients, but those modified schedules have never been prospectively tested.
- In elderly patients, a reasonable upfront treatment is a fluoropyrimidine-based monotherapy plus bevacizumab, irrespectively of the molecular status of RAS.
- BRAF mutation is a strong negative prognostic factor associated to advanced age, poor performance status (PS), extended and aggressive disease and is associated to a lack of benefit from anti-EGFR moAb.
- Clinical definition of elderly (over 70 years old) CRC patients that may deserve a more or less intensive combination therapy is still debated. The cut-off of 75 years old combined with ECOG PS assessment is a reasonable approach for clearly defining candidates to different approaches31.
- Several geriatric screening tools have been used to identify patients with a geriatric profile potentially predicting for overall survival and risk of toxicity. The G8 screening tool has been validated in cancer patients showing the strongest prognostic value for overall survival; the CRASH score is able to stratify patients according an estimated risk of treatment-related toxicities.
On the basis of these considerations, the investigators designed the present randomized phase II trial of first-line therapy panitumumab in combination with simplified FOLFOX or with 5-fluorouracil, in previously untreated elderly patients with RAS and BRAF wild-type unresectable mCRC.
- Being tested
- 5-fluorouracil, oxaliplatin, l-leucovorin, panitumumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-fluorouracilDrug
oxaliplatinDrug
l-leucovorinDrug
panitumumabDrug
| Study group | Role | What they receive |
|---|---|---|
| FOLFOX plus panitumumab | Experimental | * Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes;
* Oxaliplatin 85 mg/sqm iv over 2 hours, day 1;
* L-Leucovorin 200 mg/sqm iv over 2 hours, day 1;
* 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. Receives: Drug: 5-fluorouracil; Drug: oxaliplatin; Drug: l-leucovorin; Drug: panitumumab |
| 5FU/LV plus panitumumab | Experimental | * Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes;
* L-Leucovorin 200 mg/sqm iv over 2 hours, day 1;
* 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. Receives: Drug: 5-fluorouracil; Drug: l-leucovorin; Drug: panitumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS). PFS is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first.
July 2016 - November 2018
Measured: Up to 28 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2016 (estimated)
- Study startJul 2016
- Primary completion15 Nov 2019
- Study completionOct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Elderly Metastatic Colorectal Cancer PatientsStudies 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
- 180 participants (estimated)
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
- NCT02904031
- Sponsor's protocol ID
- 2015-003888-10
- Other IDs
- 2015
- Acronym
- PANDA
- Status last verified
- May 2020
- First submitted
- 11 Jul 2016
- Last updated
- 12 May 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Lonardi S, Rasola C, Lobefaro R, Rossini D, Formica V, Scartozzi M, Frassineti GL, Boscolo G, Cinieri S, Di Donato S, Pella N, Bergamo F, Raimondi A, Arnoldi E, Antonuzzo L, Granetto C, Zustovich F, Ronzoni M, Leo S, Morano F, Loupakis F, Buggin F, Zagonel V, Fassan M, Cremolini C, Boni L, Pietrantonio F; GONO Foundation Investigators. Initial Panitumumab Plus Fluorouracil, Leucovorin, and Oxaliplatin or Plus Fluorouracil and Leucovorin in Elderly Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The PANDA Trial by the GONO Foundation. J Clin Oncol. 2023 Dec 1;41(34):5263-5273. doi: 10.1200/JCO.23.00506. Epub 2023 Aug 3.
PubMed 37535876Battaglin F, Schirripa M, Buggin F, Pietrantonio F, Morano F, Boscolo G, Tonini G, Lutrino ES, Lucchetti J, Salvatore L, Passardi A, Cremolini C, Arnoldi E, Scartozzi M, Pella N, Boni L, Bergamo F, Zagonel V, Loupakis F, Lonardi S. The PANDA study: a randomized phase II study of first-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS and BRAF wild-type elderly metastatic colorectal cancer patients. BMC Cancer. 2018 Jan 25;18(1):98. doi: 10.1186/s12885-018-4001-x.
PubMed 29370781
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Study of First-Line FOLFOX Plus Panitumumab Versus 5FU Plus Panitumumab in RAS And BRAF Wild-Type Metastatic Colorectal Cancer Elderly Patients
- ClinicalTrials.gov ID
- NCT02904031
- Acronym / sponsor ID
- PANDA / 2015-003888-10
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Gruppo Oncologico del Nord-OvestUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- 15 Nov 2019 (actual)
- Study completion
- Oct 2020 (estimated)
- First posted
- 16 Sep 2016 (estimated)
- 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.
- Few data are available about the treatment of metastatic colorectal cancer (mCRC) elderly patients with anti-EGFR agents in combination with chemotherapy. Up today, most of the available data are from retrospective/post-hoc analyses, making them difficult to translate to everyday clinical practice.
- FOLFOX plus panitumumab is a standard first-line therapy option for RAS wild-type untreated mCRC patients. Slight adjustments in chemo-dosage are commonly applied in routinary practice to elderly patients, but those modified schedules have never been prospectively tested.
- In elderly patients, a reasonable upfront treatment is a fluoropyrimidine-based monotherapy plus bevacizumab, irrespectively of the molecular status of RAS.
- BRAF mutation is a strong negative prognostic factor associated to advanced age, poor performance status (PS), extended and aggressive disease and is associated to a lack of benefit from anti-EGFR moAb.
- Clinical definition of elderly (over 70 years old) CRC patients that may deserve a more or less intensive combination therapy is still debated. The cut-off of 75 years old combined with ECOG PS assessment is a reasonable approach for clearly defining candidates to different approaches31.
- Several geriatric screening tools have been used to identify patients with a geriatric profile potentially predicting for overall survival and risk of toxicity. The G8 screening tool has been validated in cancer patients showing the strongest prognostic value for overall survival; the CRASH score is able to stratify patients according an estimated risk of treatment-related toxicities.
On the basis of these considerations, the investigators designed the present randomized phase II trial of first-line therapy panitumumab in combination with simplified FOLFOX or with 5-fluorouracil, in previously untreated elderly patients with RAS and BRAF wild-type unresectable mCRC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FOLFOX plus panitumumab | Experimental | Drug: 5-fluorouracil, Drug: oxaliplatin, Drug: l-leucovorin, Drug: panitumumab* Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; * Oxaliplatin 85 mg/sqm iv over 2 hours, day 1; * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. |
| 5FU/LV plus panitumumab | Experimental | Drug: 5-fluorouracil, Drug: l-leucovorin, Drug: panitumumab* Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; * L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; * 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (16 listed)
- Written informed consent to study procedures and to molecular analyses.
- Histologically proven diagnosis of colorectal cancer.
- Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
- At least one measurable lesion according to RECIST1.1 criteria.
- Availability of a tumoral sample (primary and/or metastatic sites).
Key exclusion criteria (20 listed)
- Previous treatment for metastatic disease.
- Radiotherapy to any site within 4 weeks before the study.
- Previous adjuvant oxaliplatin-containing chemotherapy.
- Previous treatment with EGFR inhibitors.
- Untreated brain metastases or spinal cord compression or primary brain tumors.
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 |
|---|---|---|
| 5-fluorouracil | Drug | 5FU/LV plus panitumumab, FOLFOX plus panitumumab |
| oxaliplatin | Drug | FOLFOX plus panitumumab |
| l-leucovorin | Drug | 5FU/LV plus panitumumab, FOLFOX plus panitumumab |
| panitumumab | Drug | 5FU/LV plus panitumumab, FOLFOX plus panitumumab |
Primary outcome
Progression Free Survival (PFS). PFS is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first.
Time frame: Up to 28 months
July 2016 - November 2018
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2020.
- Derived from this study: PubMed 37535876Lonardi S, Rasola C, Lobefaro R, Rossini D, Formica V, Scartozzi M, Frassineti GL, Boscolo G, Cinieri S, Di Donato S, Pella N, Bergamo F, Raimondi A, Arnoldi E, Antonuzzo L, Granetto C, Zustovich F, Ronzoni M, Leo S, Morano F, Loupakis F, Buggin F, Zagonel V, Fassan M, Cremolini C, Boni L, Pietrantonio F; GONO Foundation Investigators. Initial Panitumumab Plus Fluorouracil, Leucovorin, and Oxaliplatin or Plus Fluorouracil and Leucovorin in Elderly Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The PANDA Trial by the GONO Foundation. J Clin Oncol. 2023 Dec 1;41(34):5263-5273. doi: 10.1200/JCO.23.00506. Epub 2023 Aug 3.
- Derived from this study: PubMed 29370781Battaglin F, Schirripa M, Buggin F, Pietrantonio F, Morano F, Boscolo G, Tonini G, Lutrino ES, Lucchetti J, Salvatore L, Passardi A, Cremolini C, Arnoldi E, Scartozzi M, Pella N, Boni L, Bergamo F, Zagonel V, Loupakis F, Lonardi S. The PANDA study: a randomized phase II study of first-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS and BRAF wild-type elderly metastatic colorectal cancer patients. BMC Cancer. 2018 Jan 25;18(1):98. doi: 10.1186/s12885-018-4001-x.
- 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 5-fluorouracil, oxaliplatin and l-leucovorin in people with Elderly Metastatic Colorectal Cancer Patients, 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 16 inclusion and 20 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 12 May 2020. 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?
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 (PFS). PFS is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. (time frame: Up to 28 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 NCT02904031, which also lists 2 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 12 May 2020.