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Standard of Care Alone or in Combination With Ad-CEA Vaccine and Avelumab in People With Previously Untreated Metastatic Colorectal Cancer QUILT-2.004

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03050814
Recruitment Status : Terminated (Terminated after an unplanned interim efficacy analysis.)
First Posted : February 13, 2017
Results First Posted : December 9, 2021
Last Update Posted : December 20, 2021
Sponsor:
Information provided by (Responsible Party):
Julius Strauss, M.D., National Cancer Institute (NCI)

Brief Summary:

Background:

Colorectal cancer is a common cancer in the Unites States (U.S.) It causes the second most cancer-related deaths. The drug avelumab and vaccine Ad-CEA together help the immune system fight cancer.

Objective:

To test if avelumab and Ad-CEA plus standard therapy treats colorectal cancer that has spread to other sites better than standard therapy alone.

Eligibility:

People ages 18 and older with untreated colorectal cancer that has spread in the body

Design:

Participants will be screened with:

Test to see if their cancer has a certain deficiency

Blood, urine, and heart tests

Scans

Medical history

Physical exam

Tumor sample. This can be from a previous procedure.

A small group of participants will get Ad-CEA and avelumab plus standard therapy. This is leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) plus bevacizumab for up to 24 weeks then capecitabine plus bevacizumab.

The others will have treatment in 2-week cycles. They will be Arm A or B:

Arm A: FOLFOX and bevacizumab by intravenous (IV) days 1 and 2 for 12 cycles. After that, capecitabine by mouth twice a day and bevacizumab by IV on day 1.

Arm B: Ad-CEA injection every 2-12 weeks. Avelumab by IV on day 1 of each cycle. FOLFOX and bevacizumab by IV days 2 and 3 for 12 cycles. Then, capecitabine by mouth twice a day and bevacizumab through IV on day 2.

Participants will repeat screening tests during the study.

Participants will be treated until their disease gets worse or they have bad side effects. Arm A participants can join Arm B. They will have a visit 4 5 weeks after they stop therapy.


Condition or disease Intervention/treatment Phase
Colorectal Tumors Colorectal Neoplasms Colorectal Carcinoma Colorectal Adenocarcinoma Colorectal Cancer Drug: Avelumab Biological: Ad-CEA vaccine Drug: Bevacizumab Drug: 5-Fluorouracil (FU) Drug: Leucovorin Drug: Oxaliplatin Drug: Capecitabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Standard of Care Alone or in Combination With Ad-CEA Vaccine and Avelumab in Patients With Previously Untreated Metastatic or Unresectable Colorectal Cancer
Actual Study Start Date : April 5, 2017
Actual Primary Completion Date : August 25, 2021
Actual Study Completion Date : August 25, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines
Drug Information available for: Avelumab

Arm Intervention/treatment
Active Comparator: Standard of Care (SOC) - Arm A
Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine until disease progression.
Drug: Bevacizumab
5mg/kg intravenous (IV) over 30-90 min on day 1 (Arm A) or 2 (Arm B). Part of the standard of care therapy.
Other Name: Avastin

Drug: 5-Fluorouracil (FU)
400mg/m^2 (only Arm A) intravenous (IV) bolus on day 1. Part of the standard of care therapy.
Other Name: Tolak

Drug: Leucovorin
400mg/m^2 intravenous (IV) over 2 hours on day 1 (Arm A) or Day 2 (Arm B). Part of the standard of care therapy.
Other Name: folinic acid

Drug: Oxaliplatin
85mg/m^2 (Arm A) or 68mg/m^2 (Arm B) intravenous (IV) over 2 hours on day 1 (Arm A) or Day 2 (Arm B). Part of the standard of care therapy.
Other Name: Eloxatin

Drug: Capecitabine
625 mg/m^2 twice a day by mouth. Part of the standard of care therapy.
Other Name: Xeloda

Drug: 5-Fluorouracil (FU)
2400 mg/m^2 (Arm A and B) intravenous (IV) over 46 hours (+/-2 hours) to start on Day 1 (ARM A) or Day 2 (Arm B). Part of the standard of care therapy.
Other Name: Tolak

Experimental: Standard of Care (SOC) - Arm B + Lead in
Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + avelumab + Ad-CEA vaccine (given weeks 0,2,4,8,12,16 and then every 12 weeks) for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine + avelumab + Ad-CEA vaccine (following the every 12-week dosing schedule) until disease progression.
Drug: Avelumab
10 mg/kg intravenous (IV) over 30-60 min on Day 1
Other Name: Bavencio

Biological: Ad-CEA vaccine
Subcutaneous injection in the thigh prior to Avelumab on Day 1 of cycles 1, 2 3, 5, 7, 9; every 6 cycles thereafter.

Drug: Bevacizumab
5mg/kg intravenous (IV) over 30-90 min on day 1 (Arm A) or 2 (Arm B). Part of the standard of care therapy.
Other Name: Avastin

Drug: 5-Fluorouracil (FU)
400mg/m^2 (only Arm A) intravenous (IV) bolus on day 1. Part of the standard of care therapy.
Other Name: Tolak

Drug: Leucovorin
400mg/m^2 intravenous (IV) over 2 hours on day 1 (Arm A) or Day 2 (Arm B). Part of the standard of care therapy.
Other Name: folinic acid

Drug: Oxaliplatin
85mg/m^2 (Arm A) or 68mg/m^2 (Arm B) intravenous (IV) over 2 hours on day 1 (Arm A) or Day 2 (Arm B). Part of the standard of care therapy.
Other Name: Eloxatin

Drug: Capecitabine
625 mg/m^2 twice a day by mouth. Part of the standard of care therapy.
Other Name: Xeloda

Drug: 5-Fluorouracil (FU)
2400 mg/m^2 (Arm A and B) intravenous (IV) over 46 hours (+/-2 hours) to start on Day 1 (ARM A) or Day 2 (Arm B). Part of the standard of care therapy.
Other Name: Tolak




Primary Outcome Measures :
  1. Progression Free Survival Between the Standard of Care (SOC) Arm A, and Standard of Care (SOC) Arm B + lead-in [ Time Frame: Up to 1.5 years ]
    Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.


Secondary Outcome Measures :
  1. Number of Participants That Are Hospitalized Because of Adverse Events Attributed to Disease Progression [ Time Frame: Up to 51.5 months ]
    Participants hospitalized because of adverse events measured by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 attributed to disease progression. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.


Other Outcome Measures:
  1. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) [ Time Frame: Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B. ]
    Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:
  • Subjects must have previously untreated metastatic or unresectable colorectal cancer and have no contraindications to treatment with the standard of care regimen as determined by the investigator. Prior adjuvant therapy for surgically resectable disease (including oligometastatic disease) is acceptable (including immunotherapy) but must have been completed at least 6 months prior to enrollment.
  • Patients should not be eligible for potentially curative surgical intervention in the case of oligometastatic disease at the time of enrollment or must have actively refused after explicit discussion of potential benefit of this intervention with multidisciplinary team.
  • Histologically confirmed colorectal cancer
  • Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  • Age greater than or equal to 18 years. Because safety data is not known with this agent in patients less than 18 years old, children are excluded from this study.
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
  • Patients must have normal organ and marrow function as defined below:

    • Creatinine clearance (per Institutional standard or 24-hour urine) greater than or equal to 30 mL/min.
    • Adequate hepatic function defined by a total bilirubin level less than or equal to 1.5 the upper limit of normal range (ULN), an aspartate aminotransferase (AST), level less than or equal to 2.5 ULN, and an alanine aminotransferase (ALT) level less than or equal to 2.5 ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels less than or equal to 5 ULN.
    • Hematological eligibility parameters (within16 days of enrollment):
    • Granulocyte count greater than or equal to 1,500/mm^3
    • Platelet count greater than or equal to 100,000/mm^3
    • Hemoglobin greater than or equal to 9 g/dL
  • The effects of Ad-CEA vaccine and Avelumab on the developing human fetus are unknown. For this reason and because Ad-CEA vaccine and Avelumab as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for a period of 4 months after the last treatment with avelumab or 6 months after the last administration of bevacizumab, whichever occurs later. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  • Metastatic or unresectable colorectal cancer with mismatch repair deficiency (MMR-D or microsatellite instability (MSI)-High).
  • Concurrent treatment for cancer except agents specified within the treatment protocol.
  • Prior surgery or gastrointestinal perforation within 28 days of enrollment.
  • Persisting toxicity related to prior therapy (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade > 1); however, alopecia, sensory neuropathy Grade <=2, or other Grade <=2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
  • Any significant disease that, in the opinion of the investigator, may impair the patient's tolerance of study treatment.
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses less than or equal to 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication).
  • Patients who are receiving any other investigational agents within 28 days before start of study treatment.
  • Prior organ transplantation including allogenic stem-cell transplantation.
  • Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy. Subjects with CNS metastases incidentally detected during Screening which do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is needed are eligible.
  • Active infection, requiring systemic therapy,
  • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 3 months prior to enrollment), myocardial infarction (< 3 months prior to enrollment), unstable angina, congestive heart failure (greater than or equal to New York Heart Association Classification Class II), or uncontrolled arrhythmias.
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Pregnant women and breastfeeding mothers are excluded due to unknown impact on embryos or infants.
  • Known alcohol or drug abuse.
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade greater than or equal to 3).
  • Patients with a known hypersensitivity/allergy to any of the standard of care agents used in this study or related compounds (e.g., platinum compounds) are excluded.
  • Prior history of hypertensive emergency or hypertensive encephalopathy (for those expected to receive bevacizumab.
  • Serious, non-healing wound, active ulcer, or untreated bone fracture, including tumor related pathological fracture.
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
  • Patients being treated with medications with drug-drug interactions with study agents will require evaluation by to determine if full doses of all study treatments can be given safely. Significant drug-drug interactions will need to be addressed prior to enrollment. Alternatively, the patient will not be eligible.
  • Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.

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): NCT03050814


Locations
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United States, District of Columbia
Lombardi Comprehensive Cancer Center
Washington, District of Columbia, United States, 20007
United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Julius Y Strauss, M.D. National Cancer Institute (NCI)
  Study Documents (Full-Text)

Documents provided by Julius Strauss, M.D., National Cancer Institute (NCI):
Informed Consent Form  [PDF] December 23, 2019

Additional Information:
Publications:
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Responsible Party: Julius Strauss, M.D., Principal Investigator, National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03050814    
Other Study ID Numbers: 170057
17-C-0057
First Posted: February 13, 2017    Key Record Dates
Results First Posted: December 9, 2021
Last Update Posted: December 20, 2021
Last Verified: December 2021
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
Keywords provided by Julius Strauss, M.D., National Cancer Institute (NCI):
Anti-PDL1 Antibody
Therapeutic Cancer Vaccine
Mismatch Repair Deficiency
Progression Free Survival
Adenovirus Based, CEA-Targeting Vaccine
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Bevacizumab
Avelumab
Fluorouracil
Capecitabine
Oxaliplatin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes