Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion
Principal Investigator
Shumei Kato
Photo of Shumei Kato
Shumei Kato

Description

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), 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.

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

Details

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 >= 6 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.

Keywords

Metastatic Colon Adenocarcinoma Metastatic Colorectal Carcinoma Metastatic Rectal Adenocarcinoma Stage III Colon Cancer AJCC v8 Stage III Colorectal Cancer AJCC v8 Stage III Rectal Cancer AJCC v8 Stage IIIA Colon Cancer AJCC v8 Stage IIIA Colorectal Cancer AJCC v8 Stage IIIA Rectal Cancer AJCC v8 Stage IIIB Colon Cancer AJCC v8 Stage IIIB Colorectal Cancer AJCC v8 Stage IIIB Rectal Cancer AJCC v8 Stage IIIC Colon Cancer AJCC v8 Stage IIIC Colorectal Cancer AJCC v8 Stage IIIC Rectal Cancer AJCC v8 Stage IV Colon Cancer AJCC v8 Stage IV Colorectal Cancer AJCC v8 Stage IV Rectal Cancer AJCC v8 Stage IVA Colon Cancer AJCC v8 Stage IVA Colorectal Cancer AJCC v8 Stage IVA Rectal Cancer AJCC v8 Stage IVB Colon Cancer AJCC v8 Stage IVB Colorectal Cancer AJCC v8 Stage IVB Rectal Cancer AJCC v8 Stage IVC Colon Cancer AJCC v8 Stage IVC Colorectal Cancer AJCC v8 Stage IVC Rectal Cancer AJCC v8 Unresectable Colon Adenocarcinoma Unresectable Colorectal Carcinoma Unresectable Rectal Adenocarcinoma Carcinoma Colorectal Neoplasms Adenocarcinoma Rectal Neoplasms Colonic Neoplasms Trifluridine Antineoplastic Agents, Immunological Panitumumab Antibodies Immunoglobulins Antibodies, Monoclonal Quality-of-Life Assessment Regorafenib Trifluridine and Tipiracil Hydrochloride

Eligibility

You can join if…

Open to people ages 18 years and up

  • Registered to Colorectal Cancer Liquid Biopsy Screening Protocol for Molecularly

Assigned Therapy (COLOMATE) ACCRU-GI-1611 and:

  • COLOMATE Companion Trial Recommendation Form indicates patient qualifies to be screened for a COLOMATE companion trial.
  • COLOMATE Companion Trial Recommendation Form date of completion is =< 30 days prior to randomization.
  • 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.
  • Progression, intolerance, or contraindication to a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, and an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or aflibercept), and an anti-PD-1 monoclonal antibody (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins (dMMR) or is microsatellite instability-high (MSI-H)
  • Disease progression after treatment with an anti-EGFR monoclonal antibody (cetuximab and/or panitumumab) for at least 4 months (minimum of 8 biweekly treatments or 16 weekly treatments at full or partial dose).
  • NOTE: Treatments do not need to be administered consecutively.
  • NOTE: Dose reductions or delays are permitted.
  • Greater than 90 days has elapsed between the most recent treatment with an anti-EGFR therapy (cetuximab or panitumumab) and blood collection for COLOMATE ACCRU-GI-1611.
  • 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/mm3 without colony stimulating factor support (obtained =< 7 days prior to randomization).

  • Platelet count >= 75,000 /mm3 (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 (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.

You CAN'T join if...

  • 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 2% by Guardant360 assay.
  • Detection of at least one of the following gene mutation(s) or amplification(s) by Guardant360 assay.
  • BRAF mutation mutant allele frequency (MAF) > 0.5%.
  • EGFR mutation (MAF > 0.5%). Note: EGFR S492R, K467, and R451C mutations are not an exclusion.
  • ERBB2 (HER2) mutation (MAF > 0.5%) or amplification.
  • KRAS mutation (MAF > 0.5%) or amplification.
  • MET mutation (MAF > 0.5%) or 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.

Locations

  • UC San Diego Moores Cancer Center not yet accepting patients
    La Jolla California 92093 United States
  • USC / Norris Comprehensive Cancer Center accepting new patients
    Los Angeles California 90033 United States

Lead Scientist at UCSD

  • Shumei Kato
    Assistant Clinical Professor, Medicine. Authored (or co-authored) 60 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Academic and Community Cancer Research United
ID
NCT03992456
Phase
Phase 2
Study Type
Interventional
Last Updated