A Study of Experimental Oncology Therapies Combined With Chemotherapy and Bevacizumab for Colorectal Cancer

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"Volunteer for research at UC Davis and contribute to discoveries that may improve health care for you, your family, and your community!"
Age: 18 to 101 years old
Gender:
Any
Healthy Volunteers: No
Keywords: Metastatic Microsatellite-Stable Colorectal Cancer, chemotherapy, Colorectal Cancer, metastatic cancer
Type: Drug study, Phase [/1/,/ /2/]
Target:
6 Participants
Investigator:
Description
This is a research study of experimental medications called novel oncology therapies (durvalumab and oleclumab). They will be combined with standard treatment for your type of cancer. This study is for patients who have Metastatic Microsatellite-Stable Colorectal Cancer (MSS-CRC) and have not received prior therapy. Metastatic means your cancer has spread from your colon to another part of your body.

This study has two parts: Part 1 and Part 2. The study doctor will tell you which part of the study you are being asked to take part in.

The main purpose of the first portion (Part 1) of this study is to determine the safety and effectiveness of the experimental medicines. Safety will be tested by checking for:
- side effects
- abnormal laboratory test results,
- vital signs (temperature, blood pressure, pulse rate and respiratory rate),
- electrocardiogram (ECG) results.

The main purpose of the second portion of this study (Part 2) is to compare the antitumor effect of the combination treatment in subjects with MSS-CRC.

Researchers have found that sometimes the body’s own immune system may slow down or control cancer growth. Sometimes this natural immune system response stops, and the cancer is not killed by your own immune system. Research has shown that in some patients cancer cells and immune cells start to express signals that stop the body’s immune system from killing the cancer. New drugs such as durvalumab and oleclumab are designed to block these signals and to increase the immune response.

Durvalumab is an antibody (antibodies are proteins that are produced by the body’s defense system). It targets a receptor on immune cells (receptors are proteins on the surface of a cell) called programmed cell death protein (PD-1). It is hoped that by blocking this receptor, the immune cells will once again be able to prevent or slow down cancer growth.

Durvalumab has been approved by the FDA for locally advanced or metastatic urothelial carcinoma. Durvalumab has also been approved by the FDA for locally advanced non-small cell lung cancer. Durvalumab is still in the development stage for the treatment of MSS-CRC. It is not approved for treatment of MSS-CRC, except for use in research studies like this.

Oleclumab (also known as MEDI9447) is also an antibody that binds to a molecule called CD73. The normal function of CD73 is to produce a molecule named adenosine. When too much adenosine is produced it can reduce the ability of the immune system to function. Oleclumab works by reducing CD73’s ability to produce adenosine. This helps the immune system to function, and potentially to prevent cancer growth.

Oleclumab has not been approved by the FDA and is considered to be an “experimental drug”.

FOLFOX and bevacizumab are approved anticancer medications as a treatment for your type of cancer.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion criteria:

  1. Written informed consent and any locally required authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations.
  2. Age ≥ 18 years at the time of screening.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  4. Subjects must have histologic documentation of advanced or metastatic CRC and: (a) A documented mutation test during screening and confirmed tumor locations from disease assessment for enrollment. (b) Subjects must NOT have defective DNA mismatch repair (MSI) as documented by testing. (c) Subjects must not have received any prior systemic therapy for recurrent/metastatic disease (prior adjuvant chemotherapy or radio-chemotherapy is acceptable so long as progression was not within 6 months of completing the adjuvant regimen).
  5. Subjects must have at least one lesion that is measurable by RECIST v1.1 (Eisenhauer et al, 2009).
  6. Subjects must have adequate organ function.
  7. Subjects with medical conditions requiring systemic anticoagulation (eg, atrial fibrillation) are eligible provided that both of the following criteria are met: - The subject has an in-range INR on a stable dose of oral anticoagulant or be on a stable dose of low molecular weight heparin. - The subject has no active bleeding or pathological condition that carries a high risk of bleeding. 8 Body weight >35 kg. 9. Adequate method of contraception per protocol

Exclusion criteria:

  1. History of allogeneic organ transplantation.
  2. Active or prior documented autoimmune disorders within the past 5 years.
  3. History of venous thrombosis within the past 3 months.
  4. Cardiovascular criteria: (a) Presence of acute coronary syndrome including myocardial infarction or unstable angina pectoris, other arterial thrombotic event including cerebrovascular accident or transient ischemic attack or stroke within the past 6 months. (b) New York Heart Association (NYHA) class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension. (c) History of hypertensive crisis/hypertensive encephalopathy within the past 6 months.
  5. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms.
  6. No significant history of bleeding events or gastrointestinal perforation.
  7. Uncontrolled intercurrent illness.
  8. History of another primary malignancy except for: (a) Malignancy treated with curative intent and with no known active disease ≥ 5 years of low potential risk for recurrence. (b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. (c) Adequately treated carcinoma in situ without evidence of disease.
  9. History of active primary immunodeficiency.
  10. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
  11. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  12. Any unresolved toxicity NCI CTCAE Grade > 1 from previous anticancer therapy.
  13. History of leptomeningeal disease or cord compression.
  14. Untreated central nervous system (CNS) metastases.
  15. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
  16. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
  17. Prior immunotherapy or anti-angiogenics.
  18. Receipt of live attenuated vaccine within the past 30 days.
  19. Major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days.
  20. Current or prior use of immunosuppressive medication within the past 14 days, with exceptions per protocol.
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study team will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid to take part in this research study.
Resources
Schedule
Study duration and period
There are 3 stages to this study: Screening Period, Treatment Period, and Follow Up. The screening period will last no more than 28 days. Several visits to the research site within the screening period may be needed. You will receive study treatment every 2 weeks infused. If you take part in arm S1 or E1: you will also receive an infusion every 2 weeks for 4 doses and then every 4 weeks. The site staff will contact you by telephone every 3 months and every 6 months until the end of the study.
Recruitment period
From July 24, 2019
Location
UC Davis Comprehensive Cancer Center
4501 X Street
Sacramento, CA 95817
Research Topic
Conditions:
  • Metastatic Microsatellite-stable Colorectal Cancer

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