NCI Community Oncology Research Program - Kansas City (NCORP-KC)
NCI Community Oncology Research Program - Kansas City (NCORP-KC)




NCI Community Oncology Research Program - Protocol Summary

SWOG S1613 - A Randomized Phase II Study of Trastuzumab and Pertuzumab (TP) Compared to Cetuximab and Irinotecan (CETIRI) in Advanced/Metastatic Colorectal Cancer (MCRC) with HER-2 Amplification.

The summary below serves as a brief review of the treatment plan and eligibility for the protocol.


This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
 

Please contact NCORP-KC for complete protocol information.



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GI Clinical Trial

CANCER TYPE: Colon
RESEARCH BASE: SWOG
NCT NUMBER: NCT03365882
HIPPA FORM: DOWNLOAD HIPPA FORM

Consent Form: VIEW CONSENT FORM
UPDATED ON 08/16/2018 (19:47:48)

Additional Consent Form: VIEW CONSENT FORM 2
UPDATED ON 08/16/2018 (19:47:48)

BRIEF DESCRIPTION

Advanced or metastatic colorectal ca, HER-2 positive, trastuzumab + pertuzumab vs. cetuximab + irinotecan.



NOTES


Treatment      (Supplied drugs:  pertuzumab and trastuzumab)

Arm 1:

Pertuzumab 840 mg, IV, over 60 min, Day 1, Cycle 1 only, given prior to trastuzumab

Trastuzumab 8 mg/kg, IV, over 90 min, Day 1, Cycle 1 only

Pertuzumab 420 mg, IV, over 30 min, Day 1, Cycles 2+, given prior to trastuzumab until progression or toxicity

Trastuzumab 6 mg/kg, IV, over 30 min, Day 1, Cycles 2+, until progression or toxicity

Cycle = 21 days

Arm 2:

Cetuximab 500 mg/m2, IV, over 120 min, Day 1, Cycle 1 only, given prior to irinotecan

Cetuximab 500 mg/m2, IV, over 60 min, Day 1, Cycles 2+, until progression or toxicity

Irinotecan 180 mg/m2, IV, over 90 min, Day 1, All cycles, until progression or toxicity

Cycle = 14 days

Arm 3 (Crossover):

Pertuzumab 840 mg, IV, over 60 min, Day 1, Cycle 1 only, given prior to trastuzumab

Trastuzumab 8 mg/kg, IV, over 90 min, Day 1, Cycle 1 only

Pertuzumab 420 mg, IV, over 30 min, Day 1, Cycles 2+, given prior to trastuzumab until progression or toxicity

Trastuzumab 6 mg/kg, IV, over 30 min, Day 1, Cycles 2+, until progression or toxicity

Cycle = 21 days

 

 



ELIGIBILITY

Step 1

  • Patients must have histologically or cytologically documented adenocarcinoma of the colon or rectum that is metastatic or locally advanced and unresectable.
  • All patients must have molecular testing performed in a CLIA certified lab which includes KRAS and NRAS gene and exon 15 of BRAF gene (BRAF V600E mutation). Patients with any known activating mutation in exon 2 [codons 12 and 13], exon 3 [codons 59 and 61] and exon 4 [codons 117 and 146]) of KRAS/NRAS genes and in exon 15 (BRAFV600E mutation) of BRAF gene are not eligible.
  • Patients must not have been treated with any of the following prior to Step 1 Initial Registration:
    • Cetuximab, panitumumab, or any other monoclonal antibody against EGFR or inhibitor of EGFR.
    • HER-2 targeting for treatment of colorectal cancer. Patients who have received prior trastuzumab or pertuzumab for other indications such as prior history of adjuvant or neoadjuvant breast cancer treatment prior to the development of advanced colorectal cancer are eligible.
  • Patients must not have had history of severe toxicity and intolerance to or hypersensitivity to irinotecan or any other study drug. Patients must not have had a severe infusion-related reaction during any prior therapy with pertuzumab or trastuzumab.
  • Patients must have tumor slides available for submission for HER-2 testing as described in Section 15.1. HER-2 testing must be completed by the central lab prior to Step 2 Randomization. The central lab will perform HER-2 tests in accordance with instructions provided separately.

Step 2

  • Patients must have HER-2 amplification as determined by central testing (3+ or 2+ by immunohistochemistry and HER-2 gene amplification by in situ hybridization with a ratio of HER-2 gene signals to centromere 17 signals ≥ 2.0).
  • Patients must have measurable disease that is metastatic or locally advanced and unresectable. Imaging used to assess all disease per RECIST 1.1 must have been completed within 28 days prior to Step 2 Randomization. All disease must be assessed and documented on the Baseline Tumor Assessment Form.
  • Patients must have had at least one prior regimen of systemic chemotherapy for metastatic or locally advanced, unresectable disease. Patients must have progressed following the most recent therapy. Prior treatment with irinotecan is allowed. For patients that received adjuvant chemotherapy: Prior treatment for metastatic disease is not required for patient who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy. If the patient received one line of adjuvant treatment and had disease recurrence after 6 months of completing chemotherapy, patients will only be eligible after failing one additional line of chemotherapy used to treat the metastatic or locally advanced, unresectable disease. Patients who have received ≥3 lines of systemic chemotherapy for metastatic or locally advanced, unresectable disease are not eligible.
  • Patients must have completed prior chemotherapy, immunotherapy, or radiation therapy at least 14 days prior to Step 2 Randomization and all toxicity must be resolved to CTCAE v4.0 Grade 1 (with the exception of CTCAE v4.0 Grade 2 neuropathy) prior to Step 2 Randomization.
  • Brain metastases are allowed if they have been adequately treated with radiotherapy or surgery and stable for at least 30 days prior to Step 2 Randomization. Eligible patients must be neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to Step 2 Randomization.
  • Patients must have a Zubrod Performance Status of 0 or 1. (See Section 10.4)
  • Patients must be ≥ 18 years of age.
  • Patients must have a complete physical examination and medical history within 28 days prior to Step 2 Randomization.
  • Patients must have adequate hematologic function as evidenced by all of the following within 14 days prior to Step 2 Randomization: ANC ≥ 1,500/mcL; platelets ≥ 75,000/mcL; and hemoglobin ≥ 9 g/dL.
  • Patients must have adequate hepatic function as evidenced by all of the following within 14 days prior to Step 2 Randomization: AST and ALT both ≤ 5 x institutional upper limit of normal (IULN); bilirubin ≤ 1.5 mg/dL.
  • Patients must have adequate kidney function as evidenced by calculated creatinine clearance > 30 ml/min within 14 days prior to Step 2 Randomization.
  • Patients who have had an echocardiogram performed within 6 months prior to Step 2 Randomization, must have ventricular ejection fraction (LVEF) ≥ 50% or ≥ within normal limits for the institution.
  • Patients must not have an uncontrolled intercurrent illness including, but not limited to diabetes, hypertension, severe infection, severe malnutrition, unstable angina, Class III-IV New York Heart Association (NYHA) congestive heart failure (see Section 18.1), ventricular arrhythmias, active ischemic heart disease, or myocardial infarction within 6 months prior to Step 2 Randomization.
  • Patients must not have any known previous or concurrent condition suggesting susceptibility to hypersensitivity or allergic reactions, including, but not limited to: known hypersensitivity to any of the study treatments or to excipients of recombinant human or humanized antibodies. Patients with mild or seasonal allergies may be included after discussion with the Study Chairs.
  • Patients must not be planning treatment with other systemic anti-cancer agents (e.g., chemotherapy, hormonal therapy, immunotherapy) or other treatments not part of protocol-specified anti-cancer therapy including concurrent investigational agents of any type.
  • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ, other low grade lesions such as incidental appendix carcinoid, or any other cancer from which the patient has been disease and treatment free for two years. Prostate cancer patients on active surveillance are eligible.
  • Patients must not be pregnant or nursing due to risk of fetal or nursing infant harm.
  • Patients must be given the opportunity to consent to the optional submission of tissue and blood for future research as outlined in Section 15.2.

Step 3

  • Patients must have documented disease progression as defined in Section 10.2d while on CETIRI (Arm 2) on this protocol. The Follow-up Tumor Assessment Form documenting disease progression must be submitted to SWOG prior to Step 3 Crossover Registration. Registration to Step 3 Crossover must be within 28 days of discontinuation of CETIRI protocol treatment. Patients going off treatment for any other reason are not eligible.
  • Patients must have a Zubrod Performance Status of 0 or 1. (See Section 10.4)
  • Patients must have adequate hematologic function as evidenced by all of the following within 14 days prior to Step 3 Crossover Registration: ANC ≥ 1,500/mcL; platelets ≥ 75,000/mcL; and hemoglobin ≥ 9 g/dL.
  • Patients must have adequate hepatic function as evidenced by all of the following within 14 days prior to Step 3 Crossover Registration: AST and ALT both ≤ 5 x institutional upper limit of normal (IULN); bilirubin ≤ 1.5 mg/dL.
  • Patients must have adequate kidney function as evidenced by calculated creatinine clearance > 30 ml/min within 14 days prior to Step 3 Crossover Registration.
  • Patients must have left ventricular ejection fraction (LVEF) ≥ 50% or ≥ lower limit of normal for the institution by echocardiogram within 14 days prior to Step 3 Crossover Registration.
  • Patients must have a magnesium, potassium, calcium, sodium, bicarbonate, and chloride performed within 14 days prior to Step 3 Crossover Registration. Additional timepoints are noted in Section 9.0.





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