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Trial record 29 of 176 for:    immunotherapeutic agent | colon cancer

Pembrolizumab After Chemotherapy in Treating Patients With Colorectal Cancer That Has Spread to the Liver and Who Are Undergoing Liver Surgery

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ClinicalTrials.gov Identifier: NCT03844750
Recruitment Status : Recruiting
First Posted : February 18, 2019
Last Update Posted : July 17, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
This phase II trial studies how well pembrolizumab works after chemotherapy and before liver surgery in patients with colorectal cancer that has spread to the liver. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab after chemotherapy and before liver surgery may work better in treating patients with colorectal cancer that has spread to the liver.

Condition or disease Intervention/treatment Phase
Metastatic Malignant Neoplasm in the Liver Stage IV Colorectal Cancer AJCC v8 Stage IVA Colorectal Cancer AJCC v8 Stage IVB Colorectal Cancer AJCC v8 Stage IVC Colorectal Cancer AJCC v8 Procedure: Hepatectomy Biological: Pembrolizumab Drug: FOLFOX regimen Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Preoperative Immunotherapy in Patients With Colorectal Cancer and Resectable Hepatic Metastases
Actual Study Start Date : July 12, 2019
Estimated Primary Completion Date : March 1, 2020
Estimated Study Completion Date : March 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (FOLFOX, pembrolizumab, surgery)
Patients receive between 4 and 8 FOLFOX treatments, based on the treating physician's opinion. Approximately 2 weeks after the last dose of FOLFOX, patients receive pembrolizumab IV over 30 minutes on day 1. About 2 weeks later, patients undergo hepatic resection.
Procedure: Hepatectomy
Undergo liver resection.
Other Name: Liver Resection

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Drug: FOLFOX regimen
Given IV
Other Names:
  • 5-fluorouracil
  • Leucovorin
  • Oxaliplatin




Primary Outcome Measures :
  1. Proportion of patients with a >= 2-fold increase in the tumor-infiltrating CD3+ T cells per unit area (5 high power fields) in post- versus pre pembrolizumab treatment tumor specimens. [ Time Frame: Up to 1 year ]
    Tumor-infiltrating immune cells (TIICs) will be analyzed by immunohistochemistry (IHC) in pre- and post-pembrolizumab treatment tumor specimens. The proportion of patients with a >= 2-fold increase (from pre- to post-treatment) in the number of TIICs per unit area (5 high power fields) will be calculated.


Secondary Outcome Measures :
  1. Incidence of adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 1 year ]
    Adverse events (AEs) will be analyzed including but not limited to all AEs, serious (S)AEs, and fatal AEs. Furthermore, specific immune-related AEs (irAEs) will be collected and designated as immune-related events of clinical interest (ECIs). The study will use descriptive statistics to report on the safety/toxicity.

  2. Objective response rate (ORR) to leucovorin calcium (calcium folinate), 5-fluorouracil, and oxaliplatin (FOLFOX) [ Time Frame: Up to 1 year ]
    Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  3. Partial response [PR] rate to pembrolizumab [ Time Frame: Up to 1 year ]
    Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  4. Complete response [CR] rate to pembrolizumab [ Time Frame: Up to 1 year ]
    Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  5. Pathologic response rate [ Time Frame: Up to 1 year ]
    The study will use descriptive statistics to report on pathologic response.

  6. R0 resection rate [ Time Frame: Up to 1 year ]
    The study will use descriptive statistics to report on R0 resection rate.

  7. Progression-free survival (PFS) per RECIST 1.1 [ Time Frame: At 1 year ]
    The study will use descriptive statistics to report on PFS.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed CRC with liver metastases. In addition to liver metastases, extrahepatic metastases (e.g. pulmonary metastases) may be permitted if all other eligibility criteria are met. Patients are permitted to have primary tumor in situ.
  • Achieved PR or stable disease (SD) on FOLFOX chemotherapy.

    • The number of cycles of chemotherapy prior to study entry is expected to be between 4 and 8 cycles. Any variation beyond this, including prior cancer therapies, should be discussed with the study principal investigator and surgeon.
    • Concurrent monoclonal antibody (mAb) therapy (bevacizumab, cetuximab, or panitumumab) is acceptable, however the antibody must be omitted from the final cycle of chemotherapy prior to pembrolizumab.
    • FOLFOX may be substituted with CapeOx (capecitabine plus oxaliplatin).
    • Prior dose modifications and growth factor support are permissible.
    • Some or all chemotherapy may be administered at outside (non-University of California San Francisco [UCSF]) facilities.
  • Be an appropriate candidate to undergo liver biopsy and resection (+ - ablation) of liver metastases according to the interpretation of the Multidisciplinary Gastrointestinal (GI) Tumor Board.
  • Be willing and able to provide written informed consent/assent for the trial. The patient may also provide consent for future biomedical research. However, the patient may participate in the main trial without participating in future biomedical research.
  • Have measurable disease based on RECIST 1.1 as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained after last dose of FOLFOX and prior to first dose of pembrolizumab.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
  • Absolute neutrophil count (ANC) >= 1,500/uL (within 10 days of treatment initiation).
  • Platelets >= 100,000/uL (within 10 days of treatment initiation).
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment).
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN (within 10 days of treatment initiation).

    • Creatinine clearance should be calculated per institutional standard.
  • Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 ULN (within 10 days of treatment initiation).
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x ULN (within 10 days of treatment initiation).
  • Albumin >= 2.5 mg/dL (within 10 days of treatment initiation).
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10 days of treatment initiation).
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 10 days of treatment initiation).
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication (day 1). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female patients of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.

    • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
  • Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

    • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.

Exclusion Criteria:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.

    • Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since the last dose of the previous investigational agent or device use.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • Has active hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Has received prior anti-cancer monoclonal antibody (mAb), systemic anticancer therapy other than FOLFOX (including investigational agents), targeted small molecule therapy, or radiation therapy within 14 days prior to the first dose of study treatment (day 1).

    • Note: Patients must have recovered from all adverse events (AEs) due to a previous therapies to =< grade 1 or baseline. Patients with grade 2 neuropathy or alopecia are eligible. If a patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
  • Has received FOLFOX less than 7 days prior to the first dose of study treatment (day 1). Has not recovered (i.e., =< grade 1 or at baseline) from AEs due to FOLFOX chemotherapy.

    • Note: Patients with =< grade 2 neuropathy or alopecia are exceptions to this criterion and may qualify for the study.
  • Has not recovered adequately from toxicity or complications of a surgery or other procedure, per the assessment of the treating investigator.
  • Has received liver-directed therapy such as radiotherapy or yttrium-90 in the past year.
  • Has a known additional malignancy that is progressing or has required active treatment within 5 years prior.

    • Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression by imaging for at least 4 weeks by repeat imaging [repeat imaging should be performed during the study screening]), clinically stable, and without requirement of steroid treatment for at least 14 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient?s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator. Anticoagulation that cannot be safely held to perform the liver biopsy is an example of a contraindication to participation.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received any prior immunotherapy including anti?PD-1, anti?PD-L1, or anti-PD-L2 or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137).
  • Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or to any of pembrolizumab?s excipients.
  • Has received a live vaccine within 30 days prior to first dose of the trial drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette?Gu?rin (BCG), and typhoid vaccine.

    • Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.
  • Has inferior vena cava/cardiac involvement based on imaging.
  • Has had encephalopathy in the last 6 months. Those patients on rifaximin or lactulose to control their encephalopathy are not allowed.
  • Has had a solid organ or hematologic transplant.
  • Has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including therapeutic thora- or paracentesis) is eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03844750


Contacts
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Contact: Chloe Atreya, MD, Ph.D. (877) 827-3222 cancertrials@ucsf.edu
Contact: Andy Chon (415) 476-2351 andrew.chon@ucsf.edu

Locations
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United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Chloe E. Atreya, MD, PhD    887-827-3222    cancertrials@ucsf.edu   
Principal Investigator: Chloe E. Atreya, MD, PhD         
Sponsors and Collaborators
University of California, San Francisco
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Chloe Atreya, MD, Ph.D. University of California, San Francisco

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03844750     History of Changes
Other Study ID Numbers: 187015
NCI-2018-03165 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: February 18, 2019    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Colonic Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Pembrolizumab