NCT03050814

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

Terminated Phase 2 Results posted Last updated 20 December 2021

What this trial tests

Phase 2 trial testing Avelumab in Colorectal Tumors in 30 participants. Terminated before completion.

Timeline

5 April 2017

Primary endpoint
25 August 2021

25 August 2021

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	5 April 2017
Primary completion	25 August 2021
Estimated completion	25 August 2021
Sites	2 locations across United States

Drugs / interventions tested

• Avelumab (avelumab) — full drug profile →
• Ad-CEA vaccine
• Bevacizumab (Bevacizumab-Bvzr) — full drug profile →
• 5-Fluorouracil (FU)
• Leucovorin (leucovorin) — full drug profile →
• Oxaliplatin (Oxaliplatin) — full drug profile →
• Capecitabine (capecitabine) — full drug profile →
• 5-Fluorouracil (FU)

Conditions studied

• Colorectal Tumors — all drugs for Colorectal Tumors →
• Colorectal Neoplasms — all drugs for Colorectal Neoplasms →
• Colorectal Carcinoma — all drugs for Colorectal Carcinoma →
• Colorectal Adenocarcinoma — all drugs for Colorectal Adenocarcinoma →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Colorectal Tumors or Colorectal Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Standard of Care (SOC) - Arm A	8.8	3.3 – 17.0
Standard of Care (SOC) - Arm B + Lead in	10.1	3.6 – 16.1

Number of Participants That Are Hospitalized Because of Adverse Events Attributed to Disease Progression Secondary · 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.

Group	Value	95% CI
Standard of Care (SOC) - Arm A	4
Standard of Care (SOC) - Arm B + Lead in	4

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

Group	Value	95% CI
Standard of Care (SOC) - Arm A	10
Standard of Care (SOC) - Arm B + Lead in	16

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Standard of Care (SOC) - Arm A

Serious: 9/10 (90%)

Deaths: 1/10

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

Serious: 10/16 (63%)

Deaths: 1/16

Serious adverse events (43 terms)

Reaction	System	Standard of Care (SOC) - A…	Standard of Care (SOC) - A…
Fatigue	General disorders	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—
Neutrophil count decreased	Investigations	—	—
Pain	General disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Acidosis	Metabolism and nutrition disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Ascites	Gastrointestinal disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Cardiac disorders - Other, coronary vasospasm	Cardiac disorders	—	—
Creatinine increased	Investigations	—	—
Death NOS	General disorders	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—
Hypotension	Vascular disorders	—	—
Infections and infestations - Other, ureter	Infections and infestations	—	—
Injection site reaction	General disorders	—	—
Lung infection	Infections and infestations	—	—
Nausea	Gastrointestinal disorders	—	—
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, death	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—

Other adverse events (167 terms — click to expand)

Reaction	System	Standard of Care (SOC) - A…	Standard of Care (SOC) - A…
Peripheral sensory neuropathy	Nervous system disorders	—	—
Fatigue	General disorders	—	—
Injection site reaction	General disorders	—	—
Pain	General disorders	—	—
Paresthesia	Nervous system disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Fever	General disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Nausea	Gastrointestinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Alkaline phosphatase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Diarrhea	Gastrointestinal disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Neutrophil count decreased	Investigations	—	—
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	—	—
White blood cell decreased	Investigations	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Flu like symptoms	General disorders	—	—
Mucositis oral	Gastrointestinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Headache	Nervous system disorders	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—
Platelet count decreased	Investigations	—	—
Hypertension	Vascular disorders	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—
Proteinuria	Renal and urinary disorders	—	—
Rhinorrhea	Respiratory, thoracic and mediastinal disorders	—	—
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—
Anxiety	Psychiatric disorders	—	—
Blurred vision	Eye disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Creatinine increased	Investigations	—	—
Dry mouth	Gastrointestinal disorders	—	—
Edema limbs	General disorders	—	—

Most-reported serious reactions: Fatigue, Febrile neutropenia, Infusion related reaction, Neutrophil count decreased, Pain, Abdominal pain, Acidosis, Acute kidney injury.

Data from ClinicalTrials.gov NCT03050814 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immunotherapy in colorectal cancer: current achievements and future perspective.
   Fan A, Wang B, Wang X, Nie Y, et al · · 2021 · cited 321× · PMID 34671202 · DOI 10.7150/ijbs.64077
2. Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics.
   Garg AD, More S, Rufo N, Mece O, et al · · 2017 · cited 206× · PMID 29209573 · DOI 10.1080/2162402x.2017.1386829
3. Review of PD-1/PD-L1 Inhibitors in Metastatic dMMR/MSI-H Colorectal Cancer.
   Oliveira AF, Bretes L, Furtado I. · · 2019 · cited 152× · PMID 31139574 · DOI 10.3389/fonc.2019.00396
4. Vaccine Strategies to Improve Anti-cancer Cellular Immune Responses.
   Vermaelen K. · · 2019 · cited 139× · PMID 30723469 · DOI 10.3389/fimmu.2019.00008
5. Immune Checkpoints as a Target for Colorectal Cancer Treatment.
   Passardi A, Canale M, Valgiusti M, Ulivi P. · · 2017 · cited 108× · PMID 28635639 · DOI 10.3390/ijms18061324
6. Colorectal cancer vaccines: Tumor-associated antigens <i>vs</i> neoantigens.
   Wagner S, Mullins CS, Linnebacher M. · · 2018 · cited 106× · PMID 30622371 · DOI 10.3748/wjg.v24.i48.5418
7. Predictive biomarkers of colon cancer immunotherapy: Present and future.
   Hou W, Yi C, Zhu H. · · 2022 · cited 100× · PMID 36483562 · DOI 10.3389/fimmu.2022.1032314
8. Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy.
   Morse MA, Hochster H, Benson A. · · 2020 · cited 85× · PMID 31383813 · DOI 10.1634/theoncologist.2019-0176