A Clinical Trial of Durvalumab and Tremelimumab, Administered With Radiation Therapy or Ablation in Patients With Colorectal Cancer

NCT03122509 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 17-139
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and effectiveness of two investigational drugs (drugs that are not currently approved by the FDA) given in combination with radiation therapy or ablation.

Conditions

Metastatic Colorectal Cancer

Keywords

Durvalumab; Tremelimumab; Radiation Therapy; Ablation; 17-139

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  2 years

Study Arms (2)

durvalumab and tremelimumab plus Radiotherapy (RT)

EXPERIMENTAL

Patients will receive 1500 mg durvalumab via IV infusion q4w for up to 4 doses/cycles and 75 mg tremelimumab via IV infusion q4w for up to 4 doses/cycles, and then continue 1500 mg durvalumab q4w starting on Week 16. Tremelimumab will be administered first. Durvalumab infusion will start approximately 1 hour after the end of tremelimumab infusion. The duration will be approximately 1 hour for each infusion. Radiotherapy (RT) will be performed using external beam ionizing radiation as standard therapy in accordance with institutional standard practice. RT will be initiated within 7 days after the first of durvalumab and tremelimumab.

Drug: durvalumab; Drug: tremelimumab; Radiation: Radiotherapy (RT)

durvalumab and tremelimumab plus ablation

EXPERIMENTAL

Patients will receive 1500 mg durvalumab via IV infusion q4w for up to 4 doses/cycles and 75 mg tremelimumab via IV infusion q4w for up to 4 doses/cycles, and then continue 1500 mg durvalumab q4w starting on Week 16. Tremelimumab will be administered first. Durvalumab infusion will start approximately 1 hour after the end of tremelimumab infusion. The duration will be approximately 1 hour for each infusion. The ablation will be performed percutaneously under image guidance as standard therapy at the discretion of the interventional radiologist in accordance with institutional standard practice. Ablation will be performed within 7 days after the first of durvalumab and tremelimumab.

Drug: durvalumab; Drug: tremelimumab; Procedure: ablation

Interventions

durvalumab DRUG

1500 mg durvalumab via IV infusion

Also known as: (MEDI4736)

durvalumab and tremelimumab plus Radiotherapy (RT); durvalumab and tremelimumab plus ablation

tremelimumab DRUG

75 mg tremelimumab via IV infusion

durvalumab and tremelimumab plus Radiotherapy (RT); durvalumab and tremelimumab plus ablation

Radiotherapy (RT) RADIATION

Radiotherapy (RT) will be performed using external beam ionizing radiation as standard therapy in accordance with institutional standard practice.

durvalumab and tremelimumab plus Radiotherapy (RT)

ablation PROCEDURE

Ablation will be performed percutaneously under image guidance as standard therapy at the discretion of the interventional radiologist in accordance with institutional standard practice.

durvalumab and tremelimumab plus ablation

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Histologically- or cytologically- confirmed CRC.
• Metastatic CRC.
• Subjects have received at least two standard chemotherapy regimens for which they would be considered eligible (at least one containing a 5-fluoropyrimidine), or systemic chemotherapy is not indicated in the setting of low volume metastatic disease.
• At least one tumor for which palliative RT is considered appropriate standard therapy (cohort 1); or, at least one tumor for which palliative ablation is considered appropriate standard therapy (cohort 2).
• At least one index lesion that will not undergo RT or ablation, and which is measurable based on RECIST 1.1.
• Be ≥ 18 years of age on day of signing informed consent.
• Consent for tumor biopsies (for patients enrolled in stage 1 only) and blood draws for research purposes (for all patients).
• Consent for use of available archived tissue and tumor obtained during a standard procedure, for research purposes.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for ≥ 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test within 2 weeks prior to starting treatment.
• Demonstrate adequate organ function as defined all screening labs should be performed within 4 weeks prior to treatment initiation.
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Chemotherapy, monoclonal antibody, targeted small molecule therapy, within 4 weeks prior to dose #1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent (excluding alopecia or toxicity not anticipated to interfere with planned treatment on study).
• Known or suspected MSI-H CRC.
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1, including anti-PD-1, anti-PD-L1, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, except for endocrinopathies and asymptomatic amylase/lipase.
• If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention per clinical discretion of the investigator prior to starting therapy.
• Concurrent active malignancy that requires systemic treatment.
• Known CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable without evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. The use of topical steroids is permitted.
• Active autoimmune disease requiring systemic immune suppressive treatment within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Has active, non-infectious pneumonitis.
• Active or prior documented inflammatory bowel disease.
• History of allogeneic organ transplant.
• Has an active infection requiring systemic therapy.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active and untreated Hepatitis B (e.g., HBsAg reactive) or active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• MedImmune LLC: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

durvalumab; tremelimumab; Radiotherapy

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)

Therapeutics

Results Point of Contact

• Title: Dr. Neil Segal, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

segaln@mskcc.org

646-888-4187

Study Officials

• Neil Segal, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a Simon two-stage design, phase II study. It will be conducted to determine the efficacy and safety of (1) durvalumab and tremelimumab plus RT in subjects with metastatic CRC who are undergoing RT as standard therapy; and, (2) durvalumab and tremelimumab plus ablation in subjects with metastatic CRC who are undergoing ablation as standard therapy.

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: April 20, 2017
• Study Start: April 24, 2017
• Primary Completion: April 28, 2021
• Study Completion: April 28, 2021
• Last Updated: July 6, 2022
• Results First Posted: July 6, 2022

Record last verified: 2021-04

Locations

US (1)