AMP-224, a PD-1 Inhibitor, With Stereotactic Body Radiation Therapy in Metastatic Colorectal Cancer

• Status: Completed
• Trial end date: 2017-03-07
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• T-cells are white blood cells that can find and kill germs and tumors. Cancer can keep T-cells from working. Researchers think a new drug called AMP-224 might help the T-cells in people with cancer. They think the drug might work even better when combined with a certain type of radiation therapy.

Objective:

• To study the safety and effectiveness of AMP-224 together with 1 or 3 days of stereotactic body radiation therapy (SBRT) directed to the liver.

Eligibility:

• People age 18 and older with metastatic colorectal cancer. Their cancer must have spread to the liver and not be responding to treatment.

Design:

• Participants will be screened with a medical history, physical exam, and blood and urine tests. Their tumors will be measured with computerized tomography (CT) scans or magnetic resonance imaging (MRI) of the chest, stomach, and pelvis. They will have an electrocardiogram (ECG) heart test.

• Participants will have a small part of their tumor removed by needle (biopsy).

• Participants will have 8 study visits over about 10 weeks.

• At 1 visit, they will have another tumor biopsy.

• At 1 visit, they will get a chemotherapy drug through a vein (intravenous (IV)).

• At 6 visits, they will receive AMP-224 through an IV.

• At 1 or 3 visits, they will have SBRT. Computed tomography (CT) scans will map the position of their tumor. Radiation beams of different intensities at different angles will be directed to the tumor.

• At all visits, some screening procedures may be repeated.

• After treatment ends, participants will have 7 follow-up visits over about 5 months. Blood will be drawn. Some screening procedures may be repeated.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Cyclophosphamide

Criteria

-Inclusion Criteria

1. Patients must have histopathological confirmation of Colorectal Carcinoma (CRC) by the Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering this study.

2. Patients must have progressed on or been intolerant of prior oxaliplatin and irinotecan containing chemotherapeutic regimen and have disease that is not amenable to potentially curative resection. Patients who have a known KRAS wild type tumor must have progressed or been intolerant to cetuximab or panitumumab-based chemotherapy.

3. Patients must have one focus of metastatic disease in the liver that is amenable to stereotactic body radiation therapy (SBRT) in the opinion of radiation oncology.

4. All patients enrolled will be required to have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria outside the radiation field.

5. Study patients must have disease that is amenable to pre and post treatment biopsy and be willing to undergo this.

6. Age greater than or equal 18 years

7. Life expectancy of greater than 3 months

8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

9. Patients must have acceptable organ and marrow function as defined below:

• leukocytes less than or equal to 3,000/mcL

• absolute neutrophil count less than or equal 1,500/mcL

• platelets less than or equal 100,000/mcL

• total bilirubin greater than or equal 1.5X institution upper limit of normal

• Patients are eligible with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) measuring up to 5 x ULN given the presence of liver metastasis.

• creatinine greater than 1.5X institution upper limit of normal

Or

-creatinine clearance less than or equal 45 mL/min/1.73 m(2), as calculated below, for patients with creatinine levels above institutional normal

10. Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.

11. Patients must not have other invasive malignancies within the past 3 years (with the exception of non-melanoma skin cancers, localized prostate cancer, carcinoma in situ of the cervix and non-invasive bladder cancer that has had successful curative treatment).

12. Patient must be able to understand and willing to sign a written informed consent document.

Exclusion Criteria

1. Prior immune checkpoint inhibition with anti-programmed cell death-1 (PD1)/programmed death ligand-1(PD-L1) or anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) therapy or other specific T cell targeting agents.

2. Patients who have had chemotherapy (or so-called targeted systemic therapy), large field radiotherapy, or major surgery must wait 4 weeks after completing treatment prior to entering the study.

3. Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

4. Uncontrolled intercurrent illness including, but not limited to, hypertension (systolic blood pressure (BP) greater than 160, diastolic BP greater than 100), ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes or psychiatric illness/social situations that would limit compliance with study requirements.

5. Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and the investigational agent.

6. History of chronic autoimmune disease (e.g., systemic lupus erythematosus or Wegener's granulomatosis, Addison's disease, multiple sclerosis, Graves disease, Hashimoto's thyroiditis, hypophysitis, etc.) with symptomatic disease within the 3 years before randomization. Note: Active vitiligo or a history of vitiligo will not be a basis for exclusion. In addition, a past history of certain autoimmunity eg rheumatoid arthritis or thyroiditis may be allowed per principal investigator (PI) discretion provided it has been quiescent for a minimum of three years.

7. Active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea.

8. Dementia or significantly altered mental status that would prohibit the understanding or rendering of Information and Consent and compliance with the requirements of the protocol.

9. Currently receiving immunosuppressive doses of steroids or other immunosuppressive medications (inhaled and topical steroids are permitted)

10. History of sarcoidosis syndrome

11. History of hypersensitivity reaction to human or mouse antibody products.

12. Pregnancy and breast feeding are exclusion factors. The effects of AMP-224 on the developing human fetus are unknown. Enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 3 months after the end of the treatment. 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.

13. Patients with unhealed surgical wounds for more than 30 days.

14. Patients with known sensitivity or allergy to any components of AMP-224.