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

Status
Closed
Cancer Type
Colon/Rectal Cancer
Trial Phase
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT03992456
Protocol IDs
ACCRU-GI-1623 (primary)
NCI-2019-03306
Study Sponsor
Academic and Community Cancer Research United

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.

Objectives

PRIMARY OBJECTIVE:
I. 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:
I. 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).
V. 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:
I. 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.

Eligibility

  1. 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.
  2. 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.
  3. Age >= 18 years.
  4. Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic and/ or unresectable.
  5. 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.
  6. 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).
  7. 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.
  8. 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.
  9. Life expectancy >= 3 months per estimation of investigator.
  10. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1, or 2.
  11. Absolute neutrophil count (ANC) >= 1500/mm^3 without colony stimulating factor support (obtained =< 7 days prior to randomization).
  12. Platelet count >= 75,000 /mm^3 (obtained =< 7 days prior to randomization).
  13. Hemoglobin > 8.0 g/dL (obtained =< 7 days prior to randomization).
  14. Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 7 days prior to randomization).
  15. Aspartate transaminase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior to randomization).
  16. Alanine aminotransferase (ALT) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior to randomization).
  17. 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).
  18. 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).
  19. 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.
  20. Ability to complete questionnaire(s) by themselves or with assistance.
  21. Capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  22. Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study).
  23. Willing to provide tissue and blood samples for correlative research purposes.
  24. Willing to allow transfer of tissue and blood samples, clinical information, and outcome data collected from this trial for future research.
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
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