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Metastatic Colon AdenocarcinomaPhase 2NCT03992456

Panitumumab, Regorafenib, or TAS-102, in Treating Patients With Metastatic and/or Unresectable RAS Wild-Type Colorectal Cancer

A Phase 2 study testing Panitumumab, Quality-of-Life Assessment and Questionnaire Administration in people with Metastatic Colon Adenocarcinoma and Metastatic Colorectal Carcinoma, run by Academic and Community Cancer Research United at 18 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This phase II trial studies how well retreatment with panitumumab works compared to standard of care regorafenib or trifluridine and tipiracil hydrochloride (TAS-102) in treating patients with colorectal cancer that is negative for RAS wild-type colorectal cancer has spread to other places in the body (metastatic)… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Panitumumab, Quality-of-Life Assessment and Questionnaire Administration
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
18 sitesUnited States
Study dates
24 Apr 2020to 7 Oct 2024
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

  • Most recent Guardant360 blood collection date =< 90 days prior to randomization.
  • NOTE: If a patient does not have Guardant360 test results available, enrollment in ACCRU_GI-1611 (COLOMATE) is strongly encouraged.
  • Greater than 90 days has elapsed between the most recent treatment with an anti-epidermal growth factor receptor gene (EGFR) therapy (cetuximab or panitumumab) and blood collection for Guardant360 assay.
  • Age >= 18 years.
  • Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic and/ or unresectable.
  • Documented wild-type in KRAS and NRAS (codons 12, 13, 59, 61, 117, and 146) and in BRAF codon 600, based on tumor tissue taken from primary or metastatic site prior to receipt of anti EGFR therapy.
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  • Progression, intolerance, or contraindication to:
  • A fluoropyrimidine (e.g., 5-fluorouracil or capecitabine)
  • Oxaliplatin
  • Irinotecan
  • An anti-vascular endothelial growth factor (VEGF) monoclonal antibody (including but not limited to bevacizumab, ramucirumab, or aflibercept).
  • If the tumor has deficient mismatch repair proteins (dMMR) or is microsatellite instability (MSI)-high based on tumor tissue testing, an anti-programmed death (PD)-1 monoclonal antibody (including but not limited to nivolumab or pembrolizumab).
  • Clinical or radiographic progression after treatment with an anti-EGFR monoclonal antibody (cetuximab and/or panitumumab) for at least 3 months (minimum of 6 biweekly treatments or 12 weekly treatments at full or partial dose).
  • NOTE: Treatments do not need to be administered consecutively.
  • NOTE: Dose reductions or delays are permitted.
  • At least one site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria that has not been previously irradiated; if the patient has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation.
  • Life expectancy >= 3 months per estimation of investigator.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1, or 2.
  • Absolute neutrophil count (ANC) >= 1500/mm^3 without colony stimulating factor support (obtained =< 7 days prior to randomization).
  • Platelet count >= 75,000 /mm^3 (obtained =< 7 days prior to randomization).
  • Hemoglobin > 8.0 g/dL (obtained =< 7 days prior to randomization).
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 7 days prior to randomization).
  • Aspartate transaminase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior to randomization).
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior to randomization).
  • Calculated creatinine clearance must be > 30 ml/min using the Cockcroft-Gault formula or serum creatinine < 1.5 x ULN (obtained =< 7 days prior to randomization).
  • Women of child bearing potential and male partners of women of child bearing potential must agree to use two medically accepted methods of contraception, one of them being a barrier method during the study and for 2 months after the last dose of study drug(s).
  • Negative serum pregnancy test done =< 7 days prior to randomization, for women of childbearing potential only.
  • NOTE: Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is defined as amenorrhea >= 12 consecutive months.
  • NOTE: Women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, ovarian suppression or any other reversible treatment.
  • Ability to complete questionnaire(s) by themselves or with assistance.
  • Capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study).
  • Willing to provide tissue and blood samples for correlative research purposes.
  • Willing to allow transfer of tissue and blood samples, clinical information, and outcome data collected from this trial for future research.

Who cannot join

  • Radiation therapy, hormonal therapy, biologic therapy, experimental therapy, or chemotherapy for cancer < 21 days prior to randomization.
  • Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin).
  • Maximum mutant allele frequency (highest allele frequency reported for any gene mutation) (MAF) less than 0.5% by Guardant360 assay.
  • Detection of at least one of the following gene mutation(s) or amplification(s) by Guardant360 assay.
  • BRAFV600E mutation (mutant allele frequency (MAF) >= 0.5% or amplification.
  • EGFR mutation (MAF >= 0.5%). Note: EGFR S492R, K467, and R451C mutations are not an exclusion.
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  • ERBB2 (HER2) amplification.
  • KRAS mutation (MAF >= 0.5%) or amplification.
  • MET amplification.
  • NRAS mutation (MAF >= 0.5%) or amplification.
  • Prior treatment with both TAS-102 and regorafenib (prior treatment with either TAS-102 or regorafenib is permitted).
  • Unable to swallow oral tablets (crushing of study treatment tablets is not allowed).
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. Note: This includes impaired heart function or clinically significant heart disease.
  • Not recovered to baseline or Common Terminology for Adverse Events (CTCAE) version (v)5.0 =< grade 1 from toxicity due to all prior therapies except alopecia, oxaliplatin-related neuropathy, asymptomatic electrolyte abnormalities, and other non-clinically significant adverse events.
  • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
  • Pregnant women.
  • Nursing women.
  • Men or women of childbearing potential who are unwilling to employ adequate contraception.
  • Patients with known central nervous system (CNS) metastases. Note: Patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive (based on repeat imaging >= 30 days after completion of definitive treatment), patients are asymptomatic, and no steroids to control symptoms related to CNS metastases have been administered for at least 30 days.
  • Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days prior to randomization (=< 56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • History of stroke (cerebrovascular accident), transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery =< 6 months prior to randomization.
  • History of cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers, calcium channel blockers, or digoxin =< 6 months prior to randomization.
  • Known history of congestive heart failure - New York Heart Association (NYHA) >= class II.
  • Known history of human immunodeficiency virus (HIV) seropositivity, acute or chronic active hepatitis B or C infection, or other serious chronic infection requiring ongoing treatment.
  • History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan.
  • Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from colorectal cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Note: Subjects surviving a cancer that was curatively treated and without evidence of disease or biochemical relapse (undetectable PSA for prostate cancer) for 3 or more years before randomization are allowed. All cancer treatments must be completed at least 3 years prior to randomization.
  • Uncontrolled hypertension (systolic pressure > 150 mm HG or diastolic pressure > 90 mm Hg [National Cancer Institute (NCI)-CTCAE v5.0]) on repeated measurement despite optimal medical management.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Any hemorrhage or bleeding event >= NCI CTCAE v5.0 grade 3, =< 4 weeks prior to randomization.
  • Ongoing active infection > grade 2 NCI-CTCAE v5.0.
  • Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulation given during the course of this trial.
  • EXCEPTION: Cetuximab
  • Any known history of malabsorption condition.
  • Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
  • Use of any herbal remedy (e.g. St. John's wort) =< 7 days prior to randomization.
  • Use of strong CYP3A4 inducers or inhibitors =< 7 days prior to randomization.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Aurora Cancer Care-Milwaukee West

    Wauwatosa, Wisconsin, 53226

Other trials in United States

About this study

Official title: PULSE: A Randomized, Phase II Open Label Study of PanitUmumab RechaLlenge Versus Standard Therapy After Progression on Anti-EGFR Therapy in Patients With Metastatic and/or Unresectable RAS Wild-Type Colorectal Cancer

This phase II trial studies how well retreatment with panitumumab works compared to standard of care regorafenib or trifluridine and tipiracil hydrochloride (TAS-102) in treating patients with colorectal cancer that is negative for RAS wild-type colorectal cancer has spread to other places in the body (metastatic), and/or cannot be removed by surgery (unresectable), and is negative for resistance mutations in blood. Treatment with panitumumab may interfere with the ability of tumor cells to grow and spread. Some tumors need growth factors to keep growing. Growth factor antagonists, such as regorafenib, may interfere with the growth factor and stop the tumor from growing. Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving panitumumab may work better in treating patients with colorectal cancer than with the usual treatment of regorafenib or TAS-102.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare the overall survival (OS) in molecularly selected patients with metastatic colorectal cancer (CRC) receiving panitumumab rechallenge versus standard therapy (TAS-102 or regorafenib).

SECONDARY OBJECTIVES:

  1. To compare the progression free survival (PFS) in molecularly selected patients with metastatic CRC receiving panitumumab rechallenge versus standard therapy (TAS-102 or regorafenib).

II. To define the objective response rate (ORR) in patients receiving panitumumab rechallenge versus standard therapy (TAS-102 or regorafenib).

III. To define the clinical benefit rate (CBR = complete response + partial response + stable disease >= 4 months) in patients receiving panitumumab rechallenge versus standard therapy (TAS-102 or regorafenib).

IV. To compare the safety and tolerability of panitumumab rechallenge versus standard therapy (TAS-102 or regorafenib).

  1. To compare quality of life (QOL) between panitumumab rechallenge versus standard therapy (TAS-102 or regorafenib) as measured by the linear analogue self-assessment (LASA) questionnaires.

CORRELATIVE RESEARCH OBJECTIVES:

  1. To assess plasma pharmacodynamics biomarkers of response and resistance to therapy.

II. To explore any correlation between tissue and blood based biomarkers and clinical outcomes.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive panitumumab intravenously (IV) over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5 and 8-12, or regorafenib PO once daily (QD) on days 1-21, at the discretion of the treating physician. Treatment repeats every 28 days for a maximum of 24 cycles 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 for up to 3 years after randomization.

Being tested
Panitumumab, Quality-of-Life Assessment, Questionnaire Administration, Regorafenib, Trifluridine and Tipiracil Hydrochloride
Medical subject headings
Colonic Neoplasms, Colorectal Neoplasms, Rectal Neoplasms

What participants receive

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

  • PanitumumabBiological

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

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • RegorafenibDrug

    Also called BAY 73-4506, Regorafenib Anhydrous

    Given PO

  • Trifluridine and Tipiracil HydrochlorideDrug

    Also called Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine

    Given PO

Study groups in NCT03992456
Study groupRoleWhat they receive
Arm A (panitumumab)ExperimentalPatients receive panitumumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Panitumumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Arm B (regorafenib, trifluridine and tipiracil hydrochloride)Active comparatorPatients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and 8-12, or regorafenib PO QD on days 1-21, at the discretion of the treating physician. Treatment repeats every 28 days for a maximum of 24 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Regorafenib; Drug: Trifluridine and Tipiracil Hydrochloride

What is being measured

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

  1. Overall Survival (OS)

    OS is defined as the Time from randomization to death from any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier. Overall survival will be compared between the 2 treatment arms using the un-stratified log-rank test will be used.

    Measured: 2 years

Secondary outcomes (5)

  1. Progression Free Survival (PFS)

    PFS is defined as the time from randomization to documentation of disease progression or death due to any cause, whichever is first. If the patient did not have any disease evaluation post randomization, PFS will be censored at one day after randomization. The distribution of progression free survival will be estimated using the method of Kaplan-Meier. Progression free survival will be compared between the 2 treatment arms using the log-rank test which is used for the primary endpoint analysis.

    Measured: 1 year

  2. Overall Response Rate (ORR)

    Defined as the number of patients with a complete response (CR) or partial response (PR) (as defined by the Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) divided by the number of evaluable patients in each arm. ORR will be compared between the 2 treatment arms. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

    Measured: 2 years

  3. Clinical Benefit Rate

    Defined as the number of patients with a complete response (CR), partial response (PR), or stable disease for >= 4 months (as defined by the RECIST 1.1) divided by the number of evaluable patients in each arm. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

    Measured: 4 months

  4. Incidence of Adverse Events

    The maximum grade for each type of adverse event will be recorded for each patient in each cycle. The number of patients experiencing grade 3 or higher adverse events will be compared using Chi-Square or Fisher's Exact tests.

    Measured: 2 years

  5. Patient-reported Quality of Life

    Patients reported quality of life (QOL) outcomes will be collected using the Linear Analog Self-Assessment (LASA) Questionnaire. Data will be collected each cycle. Mean values of the first question (regarding overall QOL) at each cycle will be plotted, and stratified by arm. Additional analyses using data collected from the LASA questionnaire may be performed. Score from 0-10, 0 is worse and 10 is better.

    Measured: 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 posted20 Jun 2019
  2. Study start24 Apr 2020
  3. Primary completion1 Dec 2023
  4. Study completion7 Oct 2024 (estimated)

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03992456
Sponsor's protocol ID
ACCRU-GI-1623
Other IDs
NCI-2019-03306, ACCRU-GI-1623, P30CA015083
Status last verified
Apr 2024
First submitted
18 Jun 2019
Last updated
21 May 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Panitumumab, Quality-of-Life Assessment and Questionnaire Administration in people with Metastatic Colon Adenocarcinoma and Metastatic Colorectal Carcinoma, run by Academic and Community Cancer Research United at 18 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 34 inclusion and 37 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 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 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 21 May 2024). 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?

Overall Survival (OS) (time frame: 2 years). 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 NCT03992456.

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 21 May 2024.

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