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

NCT03050814 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 17005717-C-0057
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Colorectal Tumors; Colorectal Neoplasms; Colorectal Carcinoma; Colorectal Adenocarcinoma; Colorectal Cancer

Keywords

Anti-PDL1 Antibody; Therapeutic Cancer Vaccine; Mismatch Repair Deficiency; Progression Free Survival; Adenovirus Based, CEA-Targeting Vaccine

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival Between the Standard of Care (SOC) Arm A, and Standard of Care (SOC) Arm B + lead-in

  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.

  Up to 1.5 years

Secondary Outcomes (1)

• Number of Participants That Are Hospitalized Because of Adverse Events Attributed to Disease Progression

  Up to 51.5 months

Other Outcomes (1)

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  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.

Study Arms (2)

Standard of Care (SOC) - Arm A

ACTIVE COMPARATOR

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; Drug: 5-Fluorouracil (FU); Drug: Leucovorin; Drug: Oxaliplatin; Drug: Capecitabine

Standard of Care (SOC) - Arm B + Lead in

EXPERIMENTAL

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; Biological: Ad-CEA vaccine; Drug: Bevacizumab; Drug: 5-Fluorouracil (FU); Drug: Leucovorin; Drug: Oxaliplatin; Drug: Capecitabine

Interventions

Avelumab DRUG

10 mg/kg intravenous (IV) over 30-60 min on Day 1

Also known as: Bavencio

Standard of Care (SOC) - Arm B + Lead in

Ad-CEA vaccine BIOLOGICAL

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

Standard of Care (SOC) - Arm B + Lead in

Bevacizumab DRUG

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

Also known as: Avastin

Standard of Care (SOC) - Arm A; Standard of Care (SOC) - Arm B + Lead in

5-Fluorouracil (FU) DRUG

400mg/m\^2 (only Arm A) intravenous (IV) bolus on day 1. Part of the standard of care therapy.

Also known as: Tolak

Standard of Care (SOC) - Arm A; Standard of Care (SOC) - Arm B + Lead in

Leucovorin DRUG

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.

Also known as: folinic acid

Standard of Care (SOC) - Arm A; Standard of Care (SOC) - Arm B + Lead in

Oxaliplatin DRUG

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.

Also known as: Eloxatin

Standard of Care (SOC) - Arm A; Standard of Care (SOC) - Arm B + Lead in

Capecitabine DRUG

625 mg/m\^2 twice a day by mouth. Part of the standard of care therapy.

Also known as: Xeloda

Standard of Care (SOC) - Arm A; Standard of Care (SOC) - Arm B + Lead in

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Morse MA, Chaudhry A, Gabitzsch ES, Hobeika AC, Osada T, Clay TM, Amalfitano A, Burnett BK, Devi GR, Hsu DS, Xu Y, Balcaitis S, Dua R, Nguyen S, Balint JP Jr, Jones FR, Lyerly HK. Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients. Cancer Immunol Immunother. 2013 Aug;62(8):1293-301. doi: 10.1007/s00262-013-1400-3. Epub 2013 Apr 30.

  PMID: 23624851 BACKGROUND

• Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014 Nov 27;515(7528):563-7. doi: 10.1038/nature14011.

  PMID: 25428504 BACKGROUND

• Balint JP, Gabitzsch ES, Rice A, Latchman Y, Xu Y, Messerschmidt GL, Chaudhry A, Morse MA, Jones FR. Extended evaluation of a phase 1/2 trial on dosing, safety, immunogenicity, and overall survival after immunizations with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine in late-stage colorectal cancer. Cancer Immunol Immunother. 2015 Aug;64(8):977-87. doi: 10.1007/s00262-015-1706-4. Epub 2015 May 9.

  PMID: 25956394 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Colorectal Neoplasms; Turcot syndrome

Interventions

avelumab; Bevacizumab; Fluorouracil; Leucovorin; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. Julius Y. Strauss
• Organization: National Cancer Institute

julius.strauss@nih.gov

240-858-3999

Study Officials

• Julius Y Strauss, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 13, 2017
• Study Start: April 5, 2017
• Primary Completion: August 25, 2021
• Study Completion: August 25, 2021
• Last Updated: December 20, 2021
• Results First Posted: December 9, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)