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Recurrent Colorectal CarcinomaPhase 2NCT02508077

FOLFIRI and Panitumumab in Treating Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer

A Phase 2 study testing Fluorouracil, Irinotecan Hydrochloride and Laboratory Biomarker Analysis in people with Recurrent Colorectal Carcinoma and Stage IVA Colorectal Cancer, run by City of Hope Medical Center at 4 sites in United States.

Terminated

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

Official record
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Trial summary

This phase II trial studies how well fluorouracil, leucovorin calcium, and irinotecan hydrochloride (FOLFIRI) together with panitumumab work in treating patients with colorectal cancer that expresses the RAS and B-Raf proto-oncogene, serine/threonine kinase (BRAF) wild-type genes, has spread from the original site of… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fluorouracil, Irinotecan Hydrochloride and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
4 sitesUnited States
Study dates
16 Feb 2016to 13 Sep 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Participant must have the ability to understand and the willingness to sign a written informed consent document
  • Participant must be willing to comply with study and/or follow-up procedures
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy of 3 >= months
  • Histologically confirmed colon or rectal cancer with metastatic disease
  • Extended RAS and BRAF wild type status documented on archival tumor tissue or on fresh biopsy if no archival tissue present
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  • Measurable disease defined by at least 1 lesion >= 1 cm
  • Documented objective response or stable disease lasting for 6 months or more to last prior anti-EGFR (cetuximab or panitumumab) in combination with irinotecan or FOLFIRI
  • Progression within 6 weeks following their last dose of anti-EGFR therapy
  • Treatment with a non-EGFR targeting regimen following progression on anti-EGFR plus irinotecan-based therapy
  • At least 4 months from prior anti-EGFR therapy prior to start of study treatment
  • At least three weeks from any non-anti-EGFR therapy prior to start of study treatment; any number of prior therapies is permitted
  • Adequate recovery in the investigators opinion from any clinically significant toxicity from prior therapy
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Hemoglobin (Hgb) >= 9 g/dL without transfusions
  • Platelets (PLT) >= 100 x 10^9/L without transfusions
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of normal (ULN); patient with liver metastases =< 5 x ULN
  • Total bilirubin =< ULN
  • Creatinine =< 1.5 mg/dL
  • Magnesium >= 1.2mg/dL or 0.5 mmol/L
  • Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only), to be performed locally within the screening period
  • Agreement by females of childbearing potential and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

Who cannot join

  • History of severe anti-EGFR toxicity requiring drug discontinuation or dose-modification within the first 4 months of prior anti-EGFR therapy
  • History of intolerance to irinotecan at dose-intensity of 125 mg/m^2/2 weeks or lower
  • History of intolerance to 5-FU at dose-intensity of 1800 mg/m^2/2 weeks or lower
  • Current use (or planned use during the treatment period) of other investigational agents, or biological, chemotherapy, radiation or other anti-tumor therapy
  • Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids, such as systemic cyclosporine and tacrolimus
  • No St John's wort supplement or other herbal supplementation is allowed while on trial; patients are not to take grapefruit juice during study treatment
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  • Use of drugs known to inhibit UDP glycosyltransferase 1 family, polypeptide A1 gene (UGT1A1), such as Atazanavir, Gemfibrozil, Indinavir, or Ketoconazole while on study treatment; (patients using these drugs must not take these drugs on the day study treatment begins and for the duration of study treatment)
  • Planned use of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors or CYP3A4 inducers while on study treatment unless deemed clinically necessary with no reasonable alternatives and with expressed permission from the principal investigator
  • If on anticoagulation, participant must be on stable therapeutic dose prior to enrollment
  • Impairment of gastrointestinal function or gastrointestinal disease (e.g., active ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, extensive small bowel resection)
  • Major surgery =< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
  • Unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic event =< 30 days before enrollment
  • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =< 6 months prior to enrollment
  • History of interstitial lung disease (ILD) eg, interstitial pneumonitis, pulmonary fibrosis or evidence of ILD on baseline chest computed tomography (CT) or magnetic resonance imaging (MRI)
  • Other active malignancies except cervical carcinomas in situ or clinically insignificant non-melanoma skin cancers
  • Clinically significant uncontrolled illness or active infections
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, 5-FU, leucovorin or any of the products to be administered during dosing
  • Pregnant women and women who are lactating; breastfeeding should be discontinued if the mother is enrolled on this study
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/psychological issues, etc
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • City of Hope Medical Center

    Duarte, California, 91010

  • City of Hope Antelope Valley

    Lancaster, California, 93534

  • City of Hope Rancho Cucamonga

    Rancho Cucamonga, California, 91730

  • South Pasadena Cancer Center

    South Pasadena, California, 91030

Other trials in United States

About this study

Official title: A Prospective Study of FOLFIRI Plus Panitumumab in Extended RAS Wild Type and BRAF Wild Type Metastatic Colorectal Cancer With Acquired Resistance to Prior Cetuximab (or Panitumumab) Plus Irinotecan-Based Therapy and Who Failed at Least One Subsequent Non-anti-EGFR Containing Regimen

This phase II trial studies how well fluorouracil, leucovorin calcium, and irinotecan hydrochloride (FOLFIRI) together with panitumumab work in treating patients with colorectal cancer that expresses the RAS and B-Raf proto-oncogene, serine/threonine kinase (BRAF) wild-type genes, has spread from the original site of growth to another part of the body (metastatic), resists the effects of treatment with prior cetuximab (or panitumumab) plus irinotecan hydrochloride-based therapy, and who have failed at least one subsequent non-anti-epidermal growth factor receptor (EGFR) containing treatment regimen. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as panitumumab, may block tumor growth in different ways by targeting certain cells. Giving FOLFIRI together with panitumumab may be an effective treatment for colorectal cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Estimate the response rate (RR) and progression-free survival (PFS) with FOLFIRI + panitumumab in patients with acquired resistance to panitumumab (or cetuximab) + irinotecan (irinotecan hydrochloride)-based therapy after a documented clinical response or prolonged PFS and following progression on a subsequent non-anti-EGFR containing regimen in extended RAS wild-type and BRAF wild-type patients.

SECONDARY OBJECTIVES:

  1. Estimate the overall survival (OS) in the re-challenge populations.

II. Describe the safety of re-challenge in this population.

III. Investigate the impact of PFS, RR on prior anti-EGFR + irinotecan-based exposure on the response and PFS on the current study.

TERTIARY OBJECTIVES:

  1. Collect serial plasma samples to investigate the incidence of RAS and BRAF mutation in circulating free deoxyribonucleic acid (DNA) at baseline, every 2 months, and at the time to progression (and following progression when feasible).

II. Collect serial plasma samples for future biomarker exploration, including the potential investigation of micro-ribonucleic acid (RNA).

OUTLINE:

Patients receive panitumumab intravenously (IV) over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium orally (PO), and fluorouracil IV over 46 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Being tested
Fluorouracil, Irinotecan Hydrochloride, Laboratory Biomarker Analysis, Leucovorin Calcium, 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.

  • FluorouracilDrug

    Also called 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU

    Given IV

  • Irinotecan HydrochlorideDrug

    Also called Campto, Camptosar, Camptothecin 11, Camptothecin-11

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given PO

  • PanitumumabBiological

    Also called ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, MoAb ABX-EGF

    Given IV

Study groups in NCT02508077
Study groupRoleWhat they receive
Treatment (panitumumab and FOLFIRI)ExperimentalPatients receive panitumumab IV over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium PO, and fluorouracil IV over 46 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Fluorouracil; Drug: Irinotecan Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Biological: Panitumumab

What is being measured

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

  1. 4-month Progression-free Survival (PFS) Rate

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Will be estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including baseline sum), or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: At 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 posted24 Jul 2015 (estimated)
  2. Study start16 Feb 2016
  3. Primary completion13 Sep 2017
  4. Study completion13 Sep 2017

Why it stopped: Poor 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
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02508077
Sponsor's protocol ID
15117
Other IDs
NCI-2015-01241, 118713, 15117
Status last verified
Jul 2018
First submitted
22 Jul 2015
Last updated
16 Aug 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fluorouracil, Irinotecan Hydrochloride and Laboratory Biomarker Analysis in people with Recurrent Colorectal Carcinoma and Stage IVA Colorectal Cancer, run by City of Hope Medical Center at 4 sites 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 22 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: stopped early, as of the sponsor's last update on 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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?

Yes. Results are posted in the registry (first posted 16 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

4-month Progression-free Survival (PFS) Rate (time frame: At 4 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 NCT02508077.

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 16 Aug 2018.

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