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Colorectal CancerPhase 1/2NCT01960023

Safety and Efficacy Study of Neratinib and Cetuximab to Treat Patients With Quadruple Wild-Type Metastatic Colorectal Cancer

A Phase 1/2 study testing Cetuximab and Neratinib in people with Colorectal Cancer, run by NSABP Foundation Inc at 12 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The FC-7 study is designed as an open label, single arm, Phase I/II dose-escalation study evaluating the combination of neratinib and cetuximab in patients with metastatic colorectal cancer primary tumor that is "quadruple wild-type " (wild-type KRAS, NRAS, BRAF, PIK3CA). 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?
Cetuximab and Neratinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
12 sitesUnited States
Study dates
Oct 2013to 13 Jul 2016
Phase
Phase 1/2
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

  • Patients with resected primary must be active participants of the NSABP Patient Registry and Biospecimen Profiling Repository (MPR-1) study. Patients with intact primary and metastatic KRAS wild-type disease at presentation (treatment naive), must have signed consent for quadruple wild-type central testing for treatment-naive tumor sample submission
  • The Eastern Cooperative Oncology Group (ECOG) performance status must be 0, 1, or 2.
  • Patients must have the ability to swallow oral medication.
  • The tumor tissue must have been determined to be KRAS, NRAS, BRAF, PIK3CA wild-type by central CLIA testing.
  • There must be documentation by PET/CT scan, CT scan, or MRI, that the patient has evidence of measurable metastatic disease per RECIST criteria.
  • Patients must have an accessible metastatic lesion for pretreatment core biopsy procurement.
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  • Unless either drug is medically contraindicated, patients must have received oxaliplatin and irinotecan as part of standard chemotherapy regimens. (This includes adjuvant therapy.)
  • Patients must have had at least one prior treatment for metastatic disease with standard chemotherapy and cetuximab in combination or as monotherapy. [Note: patients who received panitumumab instead of cetuximab are eligible.]
  • At the time of study entry, blood counts performed within 4 weeks prior to study entry must meet the following criteria: absolute neutrophil count (ANC) must be greater than or equal to 1000/mm3; Platelet count must be greater than or equal to 100,000/mm3; Hemoglobin must be greater than or equal to 9 g/dL
  • The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to study entry must be met: Total bilirubin must be less than or equal to 1.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and ALT must be less than or equal to 2.5 x ULN for the lab or less than or equal to 5 x ULN if liver metastasis;
  • Serum creatinine performed within 4 weeks prior to study entry must be less than or equal to 1.5 x ULN for the lab.
  • Female patients and male patients with female partners of reproductive potential must agree to use an effective method of contraception during therapy and for at least 6 months after the last dose of study therapy.
  • Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease must: Have a CD4 count greater than or equal to 200 cells/uL within 30 days prior to beginning study therapy; Be off all antiretroviral therapy (prophylaxis/treatment) greater than 60 days prior to beginning study therapy; Have no evidence of opportunistic infections.

Who cannot join

  • Diagnosis of anal or small bowel carcinoma.
  • Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
  • Previous therapy with any HER2 TKI (such as trastuzumab, lapatinib, neratinib, etc.) for any malignancy.
  • Symptomatic brain metastases or brain metastases requiring chronic steroids to control symptoms.
  • Active hepatitis B or hepatitis C with abnormal liver function tests.
  • Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
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  • Persistent Common Toxicity Criteria for Adverse Effects (CTCAE v4.0) greater than or equal to grade 2 diarrhea regardless of etiology.
  • Chronic daily treatment with corticosteroids with a dose of greater than or equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids).
  • CTCAE v4.0 grade 3 or 4 anorexia or nausea related to metastatic disease.
  • CTCAE v4.0 greater than or equal to grade 2 vomiting related to metastatic disease.
  • Any of the following cardiac conditions: Documented congestive heart failure; Myocardial infarction within 6 months prior to study entry; Unstable angina within 6 months prior to study entry; Symptomatic arrhythmia
  • Serious or non-healing wound, skin ulcer, or bone fracture.
  • History of bleeding diathesis or coagulopathy. (Patients on stable anticoagulant therapy are eligible.)
  • Symptomatic interstitial lung disease or definitive evidence of interstitial lung disease described on CT scan, MRI, or chest x-ray in asymptomatic patients; dyspnea at rest requiring current continuous oxygen therapy.
  • Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy greater than or equal to 12 months prior to study entry. Patients with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, colorectal carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
  • Previous serious hypersensitivity reaction to monoclonal antibodies. (Determination of "serious" hypersensitivity reaction is at the investigator's discretion.)
  • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
  • Pregnancy or lactation at the time of study entry.
  • Use of any investigational agent within 4 weeks prior to study entry.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • Saint Luke's Mountain States Tumor Institute

    Boise, Idaho, 83712

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • University of Florida

    Gainesville, Florida, 32610

  • MD Anderson Cancer Center Orlando

    Orlando, Florida, 32806

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15215

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • Reading Hospital and Medical Center

    West Reading, Pennsylvania, 19611

Other trials in United States

About this study

Official title: A Phase I/II Dose-Escalation Study Evaluating the Combination of Neratinib and Cetuximab in Patients With "Quadruple Wild-Type" (KRAS/NRAS/BRAF/PIK3CA Wild-Type) Metastatic Colorectal Cancer Resistant to Cetuximab

The FC-7 study is designed as an open label, single arm, Phase I/II dose-escalation study evaluating the combination of neratinib and cetuximab in patients with metastatic colorectal cancer primary tumor that is "quadruple wild-type " (wild-type KRAS, NRAS, BRAF, PIK3CA). The primary aim in the Phase I portion of this study is to determine the safety and tolerability of the two-drug combination. The primary aim of the Phase II part is to determine the overall objective response rate (complete and partial responses) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Patients will receive concurrent therapy with cetuximab (400 mg/m2 IV loading dose followed by 250 mg/m2 IV weekly), and neratinib.

Read the detailed description

The neratinib dose-escalation using a 3+3 design will include 4 dose levels (120 mg, 160 mg, 200 mg, and 240 mg) as a daily oral dose. Up to 12 patients will be treated at the maximum tolerated dose (MTD).

The neratinib dose-escalation for the study will proceed on the basis of dose-limiting toxicity (DLT) during cycle 1. DLT will be defined as the occurrence of 1 or more of the following events during cycle 1: any grade diarrhea that is associated with fever or dehydration requiring IV fluids; grade 3 diarrhea lasting more than 2 days on optimal medical therapy; grade 4 diarrhea of any duration; grade 3 or 4 neutropenia associated with fever; grade 4 neutropenia lasting more than 7 days; grade 4 thrombocytopenia; grade 3 or 4 non-hematological toxicity (excluding grade 3 rash or allergic reaction/hypersensitivity); or any toxicity-related delay of more than 2 weeks to initiate cycle 2. Patients will be enrolled at the next dose level when all evaluable patients at the same dose level have completed the first treatment cycle. Enrolled patients will remain on the assigned dose level treatment until toxicity or disease progression.

The Phase II part of this study will proceed with a two-stage design with a maximum of 46 patients. Between 6 and 12 patients at the Phase I MTD level will be included in the Phase II, stage-one analysis.

Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0.

Submission of tumor and blood samples for FC-7 correlative science studies will be a study requirement for all patients. A core biopsy procedure to procure fresh tumor samples from an accessible site of metastasis will be performed before study dose level assignment (after the patient has signed the consent form and has been screened for eligibility).

Optional biopsy samples of metastatic disease will be procured from consenting patients after Cycle 1 of treatment and at the time of disease progression.

Being tested
Cetuximab, Neratinib
Keywords
Colorectal cancer, KRAS, BRAF, NRAS, PIK3CA, NSABP
Medical subject headings
Colorectal Neoplasms, Hereditary Sensory and Autonomic Neuropathies

What participants receive

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

  • CetuximabDrug

    400 mg/m2 IV loading dose followed by weekly cetuximab 250 mg/m2 IV until disease progression

  • NeratinibDrug

    Phase I portion of the study:

    Dose level 1: 120 mg/day; Dose level 2: 160 mg/day; Dose level 3: 200 mg/day; Dose level 4: 240 mg/day

    Phase II portion of the study: The recommended dose determined in the Phase I portion of the study.

Study groups in NCT01960023
Study groupRoleWhat they receive
Arm 1: Cetuximab and NeratinibExperimentalCetuximab 400 mg/m2 IV loading dose followed by weekly cetuximab 250 mg/m2 IV plus neratinib per oral daily until disease progression
Receives: Drug: Cetuximab; Drug: Neratinib

What is being measured

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

  1. The safety and tolerability of cetuximab and neratinib during the Phase I portion of the study.

    Number of patients experiencing dose limiting toxicities (DLT).

    Measured: From start of study therapy weekly through disease progression or end of therapy, approximately 2 years

  2. Number of patients with Overall response rate (ORR)(complete response/partial response) and progression free survival (PFS) during the Phase II portion of the study

    Response as measured by RECIST 1.1 criteria.

    Measured: From start of study through 16 weeks.

Secondary outcomes (4)

  1. Progression-free survival (PFS). The time to progression and the time to progression based on tumor HER2 status.

    Measured: From start of study through disease progression or end of therapy, approximately 2 years

  2. Tumor measurement to determine objective tumor decrease and stable disease

    Measurement of disease status by continuous tumor measurement.

    Measured: From start of study through desease progression or end of therapy, approximately 2 years

  3. Measure molecular and genetic correlatives for neratinib and cetuximab

    Measured: Baseline (prior to treatment assignment), prior to therapy, after completion of cycle 1, and at disease progression approximately 2 years.

  4. The frequency and severity of adverse events to evaluate the overall toxicity in the Phase II portion of the study.

    Measured: From start of study therapy through 30 days after end of therapy, approximately 2 years

Timeline

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

  1. First posted10 Oct 2013 (estimated)
  2. Study startOct 2013
  3. Primary completion13 Jul 2016
  4. Study completion13 Jul 2016

Why it stopped: This registry was planned to report on the Phase II portion of the study. NSABP decided not to proceed with the Phase II portion of the study.

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01960023
Sponsor's protocol ID
NSABP FC-7
Status last verified
Oct 2021
First submitted
17 Sep 2013
Last updated
27 Oct 2021
Results posted
No
Data monitoring committee
No

Publications

  • Jacobs SA, Lee JJ, George TJ, Wade JL 3rd, Stella PJ, Wang D, Sama AR, Piette F, Pogue-Geile KL, Kim RS, Gavin PG, Lipchik C, Feng H, Wang Y, Finnigan M, Kiesel BF, Beumer JH, Wolmark N, Lucas PC, Allegra CJ, Srinivasan A. Neratinib-Plus-Cetuximab in Quadruple-WT (KRAS, NRAS, BRAF, PIK3CA) Metastatic Colorectal Cancer Resistant to Cetuximab or Panitumumab: NSABP FC-7, A Phase Ib Study. Clin Cancer Res. 2021 Mar 15;27(6):1612-1622. doi: 10.1158/1078-0432.CCR-20-1831. Epub 2020 Nov 17.

    PubMed 33203645

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cetuximab and Neratinib in people with Colorectal Cancer, run by NSABP Foundation Inc at 12 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 13 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: withdrawn, as of the sponsor's last update on 27 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 withdrawn before enrolling participants, so there are no results.

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?

The safety and tolerability of cetuximab and neratinib during the Phase I portion of the study. (time frame: From start of study therapy weekly through disease progression or end of therapy, approximately 2 years). The study lists 2 primary outcomes in all. 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 NCT01960023, 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 27 Oct 2021; AzTrials last refreshed its copy on 8 Nov 2026.

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