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Trial record 1 of 1 for:    NRG-GI005
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Circulating Tumor DNA Testing in Predicting Treatment for Patients With Stage IIA Colon Cancer After Surgery

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ClinicalTrials.gov Identifier: NCT04068103
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : January 28, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Tracking Information
First Submitted Date  ICMJE August 22, 2019
First Posted Date  ICMJE August 28, 2019
Last Update Posted Date January 28, 2020
Actual Study Start Date  ICMJE December 16, 2019
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • Clearance of circulating tumor deoxyribonucleic acid (ctDNA) (to undetectable levels) for the "baseline ctDNA detected" patient subset (Phase II) [ Time Frame: Baseline up to 6 months ]
    A two by two contingency table of clearance by treatment arm will be created. The one-sided Fisher exact p-value will be used to determine futility based on the rule specified. Degenerate tables where the Fisher p-value cannot be calculated (no patients clear on either arm or all patients clear on both arms) will count as a failure and a recommendation for early termination.
  • Recurrence-free survival (RFS) the "baseline ctDNA detected" patient subset (Phase III) [ Time Frame: Time to recurrence or death, assessed up to 3 years ]
    RFS will be compared by treatment arm using the logrank test with no stratification in the intent to treat (ITT) cohort. Kaplan Meier curves will be computed to describe the distribution of time to event. A summary hazard ratio and associated confidence interval will be computed from a Cox model with treatment arm as the only covariate.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • RFS [ Time Frame: Up to 3 years ]
    According to ctDNA marker status and treatment. Kaplan Meier analyses to describe the distribution of time to event for each marker-treatment combination.
  • Overall survival (OS) [ Time Frame: Up to 3 years ]
    According to ctDNA marker status and treatment. Kaplan Meier analyses to describe the distribution of time to event for each marker-treatment combination. The unstratified logrank test will be used to compare treatments for patients ?ctDNA positive? at baseline and a Cox model will estimate the hazard ratio.
  • Time to recurrence (TTR) [ Time Frame: Up to 3 years ]
    According to ctDNA marker status and treatment. Kaplan Meier analyses to describe the distribution of time to event for each marker-treatment combination. The unstratified logrank test will be used to compare treatments for patients ?ctDNA positive? at baseline and a Cox model will estimate the hazard ratio.
  • Compliance with adjuvant chemotherapy and/or active surveillance [ Time Frame: Up to 3 years ]
    The duration of chemotherapy will be categorized as none, less than 3 months, and at least 3 months by treatment arm and baseline ctDNA status. Arms will be compared by a chi square test within each baseline ctDNA status.
  • Incidence (presence or absence) of ctDNA in blood following resection of stage II colon cancer [ Time Frame: Up to 3 years ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: January 24, 2020)
  • Quantitative ctDNA levels [ Time Frame: Up to 3 years ]
    Will be associated with time to event outcomes (RFS, OS, and TTR) by treatment received.
  • Genomic profiles [ Time Frame: Up to 3 years ]
    Will be associated with TTR. Will be determined using a ctDNA assay in patients with resected stage IIA colon cancer.
  • Cost effectiveness of the use of ctDNA versus standard of care [ Time Frame: Up to 3 years ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Circulating Tumor DNA Testing in Predicting Treatment for Patients With Stage IIA Colon Cancer After Surgery
Official Title  ICMJE Phase II/III Study of Circulating Tumor DNA as a Predictive Biomarker in Adjuvant Chemotherapy in Patients With Stage IIA Colon Cancer (COBRA)
Brief Summary This phase II/III trial studies how well circulating tumor deoxyribonucleic acid (ctDNA) testing in the blood works in predicting treatment for patients with stage IIA colon cancer after surgery. ctDNA are circulating tumor cells that are shed by tumors into the blood. Finding ctDNA in the blood means that there is very likely some small amounts of cancer that remain after surgery. However, this cancer, if detected, cannot be found on other tests usually used to find cancer, as it is too small. Testing for ctDNA levels may help identify patients with colon cancer after surgery who do benefit, and those who do not benefit, from receiving chemotherapy.
Detailed Description

PRIMARY OBJECTIVES:

I. To compare the rate of ctDNA clearance in "ctDNA detected" patients treated with or without adjuvant chemotherapy following resection of stage IIA colon cancer. (Phase II) II. To compare recurrence-free survival (RFS) in "ctDNA detected" patients treated with or without adjuvant chemotherapy following resection of stage IIA colon cancer. (Phase III)

SECONDARY OBJECTIVES:

I. To describe the prevalence of detectable ctDNA in patients with stage IIA colon cancer following surgical resection.

II. To estimate time-to-event outcomes (overall survival [OS], recurrence-free survival [RFS], and time to recurrence [TTR]) by ctDNA marker status and treatment for patients with resected stage IIA colon cancer.

III. To estimate the rate of compliance with adjuvant chemotherapy and/or active surveillance for patients with resected stage IIA colon cancer.

EXPLORATORY OBJECTIVES:

I. To describe the association of quantitative ctDNA levels with time to event outcomes (RFS, OS, and TTR).

II. To characterize genomic profiles associated with recurrence using a ctDNA assay in patients with resected stage IIA colon cancer.

III. To model the cost effectiveness of the use of ctDNA versus standard of care in this setting.

IV. To evaluate performance of a ctDNA assay after incorporation of patient tumor and peripheral blood mononuclear cells.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (BLOOD STORED AND TESTED FOR ctDNA LATER): Patients undergo active surveillance.

ARM II (BLOOD TESTED FOR ctDNA AT BASELINE): Patients are assigned to 1 of 2 groups.

GROUP I (ctDNA DETECTED): At the discretion of the investigator, patients receive either oxaliplatin intravenously (IV) over 2 hours on day 1, leucovorin IV over 2 hours on day 1, and fluorouracil IV bolus over 2-4 minutes on day 1 and then by continuous IV over 46-48 hours repeated every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or oxaliplatin IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (BID) on days 1-14 repeated every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

GROUP II (ctDNA NOT DETECTED): Patients undergo active surveillance.

After completion of study treatment, patients are followed up at 12 months and then every 6 months for 2 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colon Adenocarcinoma
  • Stage IIA Colon Cancer AJCC v8
Intervention  ICMJE
  • Drug: Capecitabine
    Given PO
    Other Names:
    • Ro 09-1978/000
    • Xeloda
  • Drug: Fluorouracil
    Given IV
    Other Names:
    • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
    • 5-Fluorouracil
    • 5-Fluracil
    • 5-FU
    • AccuSite
    • Carac
    • Fluoro Uracil
    • Fluouracil
    • Flurablastin
    • Fluracedyl
    • Fluracil
    • Fluril
    • Fluroblastin
    • Ribofluor
    • Ro 2-9757
    • Ro-2-9757
  • Drug: Leucovorin
    Given IV
    Other Name: Folinic acid
  • Drug: Leucovorin Calcium
    Given IV
    Other Names:
    • Adinepar
    • Calcifolin
    • Calcium (6S)-Folinate
    • Calcium Folinate
    • Calcium Leucovorin
    • Calfolex
    • Calinat
    • Cehafolin
    • Citofolin
    • Citrec
    • citrovorum factor
    • Cromatonbic Folinico
    • Dalisol
    • Disintox
    • Divical
    • Ecofol
    • Emovis
    • Factor, Citrovorum
    • Flynoken A
    • Folaren
    • Folaxin
    • FOLI-cell
    • Foliben
    • Folidan
    • Folidar
    • Folinac
    • Folinate Calcium
    • folinic acid
    • Folinic Acid Calcium Salt Pentahydrate
    • Folinoral
    • Folinvit
    • Foliplus
    • Folix
    • Imo
    • Lederfolat
    • Lederfolin
    • Leucosar
    • leucovorin
    • Rescufolin
    • Rescuvolin
    • Tonofolin
    • Wellcovorin
  • Drug: Oxaliplatin
    Give IV
    Other Names:
    • 1-OHP
    • Ai Heng
    • Aiheng
    • Dacotin
    • Dacplat
    • Diaminocyclohexane Oxalatoplatinum
    • Eloxatin
    • Eloxatine
    • JM-83
    • Oxalatoplatin
    • Oxalatoplatinum
    • RP 54780
    • RP-54780
    • SR-96669
  • Other: Patient Observation
    Undergo active surveillance
    Other Names:
    • Active Surveillance
    • deferred therapy
    • expectant management
    • observation
    • Watchful Waiting
Study Arms  ICMJE
  • Active Comparator: Arm I (blood stored and tested for ctDNA later)
    Patients undergo active surveillance.
    Intervention: Other: Patient Observation
  • Experimental: Arm II (blood tested for ctDNA at baseline)

    Patients are assigned to 1 of 2 groups.

    GROUP I (ctDNA DETECTED): At the discretion of the investigator, patients receive either oxaliplatin IV over 2 hours on day 1, leucovorin IV over 2 hours on day 1, and fluorouracil IV bolus over 2-4 minutes on day 1 and then by continuous IV over 46-48 hours repeated every 14 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or oxaliplatin IV over 2 hours on day 1 and capecitabine PO BID on days 1-14 repeated every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity at the discretion of the investigator.

    GROUP II (ctDNA NOT DETECTED): Patients undergo active surveillance.

    Interventions:
    • Drug: Capecitabine
    • Drug: Fluorouracil
    • Drug: Leucovorin
    • Drug: Leucovorin Calcium
    • Drug: Oxaliplatin
    • Other: Patient Observation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 24, 2020)
1408
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE July 1, 2024
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Histologically/pathologically confirmed stage IIA adenocarcinoma of the colon (T3, N0, M0) with at least 12 lymph nodes examined at the time of surgical resection.
  • Appropriate for active surveillance (i.e., no adjuvant chemotherapy) at the discretion of and as documented by the evaluating oncologist based on current practice patterns.
  • The distal extent of the tumor must be >= 12 cm from the anal verge on pre-surgical endoscopy (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation). If the patient did not undergo a pre-surgical endoscopy, then the distal extent of the tumor must be >= 12 cm from the anal verge as determined by surgical examination or pre-operative imaging.
  • The patient must have had an en bloc complete gross resection of tumor (curative resection) as definitive surgical cancer treatment within 14 to 60 days of study randomization. Patients who have had a two-stage surgical procedure to first provide a decompressive colostomy and then, in a later procedure, to have the definitive surgical resection, are eligible.
  • Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling.
  • Absolute neutrophil count (ANC) must be >= 1200/mm^3 (within 28 days before randomization).
  • Platelet count must be >= 100,000/mm^3 (within 28 days before randomization); and
  • Hemoglobin must be >= 9 g/dL (within 28 days before randomization).
  • Total bilirubin must be =< ULN (upper limit of normal) for the lab (within 28 days before randomization) unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert?s disease or similar syndrome involving slow conjugation of bilirubin; and
  • Alkaline phosphatase must be < 2.5 x ULN for the lab (within 28 days before randomization); and
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be < 1.5 x ULN for the lab (within 28 days before randomization).
  • Serum creatinine =< 1.5 x ULN for the lab or measured or calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault formula for patients with creatinine levels > 1.5 x ULN for the lab (within 28 days before randomization).
  • Pregnancy test (urine or serum according to institutional standard) done within 14 days before randomization must be negative (for women of childbearing potential only).
  • Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of international normalized ratio (INR) if they are randomized to Arm 2 and receive capecitabine.

Exclusion Criteria:

  • Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.).
  • Pathologic, clinical, or radiologic evidence of metastatic disease. This includes isolated, distant, or non-contiguous intra-abdominal metastases, even if resected (including the presence of satellite nodules constituting N1c disease in the absence of lymph node involvement).
  • Tumor-related bowel perforation.
  • History of prior invasive colon malignancy, regardless of disease-free interval.
  • History of organ transplantation.
  • Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer (e.g., primary rectal adenocarcinomas for which treatment with neoadjuvant chemoradiation is warranted are not permitted).
  • Other invasive malignancy within 5 years before randomization. Exceptions are colonic polyps, non-melanoma skin cancer or carcinoma-in-situ of the cervix.
  • Synchronous primary rectal and/or colon cancers.
  • Antineoplastic therapy (e.g., chemotherapy, targeted therapy, or immunotherapy) within 5 years before randomization. (For the purposes of this study, hormonal therapy is not considered chemotherapy.).
  • Uncontrolled cardiac disease, in the opinion of the treating medical oncologist, that would preclude the use of any of the drugs included in the GI005 treatment regimen. This includes but is not limited to:

    • Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker.
    • Ventricular tachycardia or supraventricular tachycardia that requires treatment with class Ia antiarrhythmic drugs (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted.
    • Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker.
    • Complete left bundle branch block (LBBB) unless treated with a permanent pacemaker.
  • Sensory or motor neuropathy >= grade 2, according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
  • Active seizure disorder uncontrolled by medication.
  • Active or chronic infection requiring systemic therapy.
  • Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency.
  • Pregnancy or lactation at the time of randomization.
  • Co-morbid illnesses or other concurrent disease that, in the judgement of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04068103
Other Study ID Numbers  ICMJE NRG-GI005
NCI-2019-01068 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GI005 ( Other Identifier: NRG Oncology )
NRG-GI005 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party NRG Oncology
Study Sponsor  ICMJE NRG Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Van K Morris NRG Oncology
PRS Account NRG Oncology
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP