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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

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ClinicalTrials.gov Identifier: NCT03050814
Recruitment Status : Recruiting
First Posted : February 13, 2017
Last Update Posted : August 10, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Colorectal cancer is a common cancer in the 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 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 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-FU Drug: Leucovorin Drug: Oxaliplatin Drug: Capecitabine Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 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
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : August 1, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Active Comparator: A /FOLFOX-A alone
Suubjects will receive FOLFOX + bevacizumab + for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine until disease progression.
Drug: Bevacizumab
5mg/kg IV over 30-90 min on day 1 (Arm A) or 2 (Arm B). Part of the standard of care therapy.

Drug: 5-FU
400mg/m2 (only Arm A) IV bolus on day 1. Part of the standard of care therapy.

Drug: Leucovorin
400mg/m2 IV over 2 hours on day 1 (Arm A) or Day 2 (Arm B). Part of the standard of care therapy.

Drug: Oxaliplatin
85mg/m2 (Arm A) or 68mg/m2 (Arm B) IV over 2 hours on day 1 (Arm A) or Day 2 (Arm B). Part of the standard of care therapy.

Drug: Capecitabine
625 mg/m2 twice a day by mouth. Part of the standard of care therapy.

Drug: 5-FU
2400 mg/m2 (Arm A and B) IV over 46 hours (+/-2 hours) to start on Day 1 (ARM A) or Day 2 (Arm B). Part of the stanard of care therapy.

Experimental: B/Lead in, FOLFOX-A + aVELUMAB + Ad-CEA
Subjects will receive 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 IV over 30-60 min on Day 1

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 IV over 30-90 min on day 1 (Arm A) or 2 (Arm B). Part of the standard of care therapy.

Drug: 5-FU
400mg/m2 (only Arm A) IV bolus on day 1. Part of the standard of care therapy.

Drug: Leucovorin
400mg/m2 IV over 2 hours on day 1 (Arm A) or Day 2 (Arm B). Part of the standard of care therapy.

Drug: Oxaliplatin
85mg/m2 (Arm A) or 68mg/m2 (Arm B) IV over 2 hours on day 1 (Arm A) or Day 2 (Arm B). Part of the standard of care therapy.

Drug: Capecitabine
625 mg/m2 twice a day by mouth. Part of the standard of care therapy.

Drug: 5-FU
2400 mg/m2 (Arm A and B) IV over 46 hours (+/-2 hours) to start on Day 1 (ARM A) or Day 2 (Arm B). Part of the stanard of care therapy.




Primary Outcome Measures :
  1. Progression free survival. [ Time Frame: 18 months after first dose ]
    Proportion of patients that have progressive disease after 18 months


Secondary Outcome Measures :
  1. Safety [ Time Frame: 30 days after treatment discontinuation ]
    list of adverse event frequency

  2. Immunologic analysis of samples from peripheral blood [ Time Frame: 3-4 years ]
    Immunologic analysis of samples from peripheral blood

  3. Immunologic analysis of samples from tumor [ Time Frame: 3-4 years ]
    Immunologic analysis of samles from tumor

  4. Overall response rate [ Time Frame: every 2 months until disease progression ]
    Proportion of patients whose tumors shrunk after therapy

  5. Correlative analysis of immune endpoints with clinical outcomes [ Time Frame: Progression ]
    Correlation between immune endpoints and median amount of time it takes disease to worsen after treatment

  6. Overall survival [ Time Frame: death ]
    Median amount of time subject survives after therapy.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (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 is acceptable (including immunotherapy), but must have been completed at least 6 months prior to metastatic disease diagnosis.
  • Patients should not be eligible for potentially curative surgical intervention in the case of oligometastic 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 RECIST criteria.
  • Age greater than or equal to18 years. Because safety data is not known with this agent in patients less than 18 years old, children are excluded from this study.
  • ECOG performance status less than or equal to 1.
  • Patients must have normal organ and marrow function as defined below:

    • Creatinine clearance (Cockroft-Gault calculated 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 (SqrRoot) the upper limit of normal range (ULN), an aspartate aminotransferase (AST), level less than or equal to 2.5 (SqrRoot) ULN, and an alanine aminotransferase (ALT) level less than or equal to 2.5 (SqrRoot) ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels less than or equal to 5 (SqrRoot) 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 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 (NCI 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 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., 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 (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (greater than or equal to New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  • 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 crisis or hypertensive encephalopathy.
  • Serious, non-healing wound, active ulcer, or untreated bone fracture, including tumorrelated 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


Contacts
Contact: Sheri A McMahon, R.N. (240) 760-6085 smcmahon@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Julius Y Strauss, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03050814     History of Changes
Other Study ID Numbers: 170057
17-C-0057
First Posted: February 13, 2017    Key Record Dates
Last Update Posted: August 10, 2018
Last Verified: August 7, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( 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:
Colorectal Neoplasms
Adenocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Vaccines
Fluorouracil
Antibodies, Monoclonal
Bevacizumab
Oxaliplatin
Capecitabine
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites