Print Friendly Page

Protocol No. NCI10021

Principal Investigator Uboha, Nataliya

Phase II

Age Group Adult

Scope National

Sponsor Type Externally Peer-Reviewed; Institutional

Title A Phase 2 Study of MEDI4736 (durvalumab) and Tremelimumab Alone or in Combination with High or Low-Dose Radiation in Metastatic Colorectal and NSCLC

Objective The purpose of this study is to test any good and bad effects of the experimental study drugs, MEDI4736 (durvalumab) and tremelimumab given alone or in combination with either low or higher doses of radiation.

Treatment MEDI4736 (durvalumab) and tremelimumab are not yet approved by the FDA. This investigational approach could shrink your cancer, but it could also cause side effects. Researchers do not yet know what those side effects are. In order to be effective these investigational drugs will need to shrink your tumors by 25%.

Description In this study there are two disease treatment groups, Cohort 1 for Non Small Cell Lung Cancer (NSCLC) and Cohort 2 for Colorectal cancer. In Cohort 1 there are three possible treatment options: Group 1 will receive MEDI4736(durvalumab) & tremelimumab only; Group 2 will receive MEDI4736(durvalumab) & tremelimumab and 3 radiation treatments delivered on 3 different days; and Group 3 will receive MEDI4736(durvalumab) & tremelimumab and 4 radiation treatments delivered twice a day for 2 days during each of the first 4 cycles of treatment. In Cohort 2 there are two possible treatment options: Group 1 will receive MEDI4736(durvalumab) & tremelimumab and 3 radiation treatments delivered on 3 different days and Group 2 will receive MEDI4736(durvalumab) & tremelimumab and 4 radiation treatments delivered twice a day for 2 days during each of the first 4 cycles of treatment. Both tremelimumab and MEDI4736 are given via IV infusion.

Key Eligibility
  • Patients must have histologically or cytologically confirmed non-small cell lung cancer (cohort 1) or colorectal cancer (cohort 2)
  • Patients must have measurable disease
  • Patients in both cohorts must have progressive disease following prior therapy. Cohort 1 (NSCLC): Patients must have evidence of radiologic or clinical disease progression during previous treatment with systemic PD-1 directed therapy and/or have been deemed not to derive clinical benefit from PD-1 directed treatment. This includes patients who demonstrated an initial response and subsequent progression. No prior treatment with chemotherapy or targeted agents are required. For Cohort 2 (Colorectal cancer): Patients must have progressed on first-line chemotherapy
  • Age ≥18 years
  • Patients must have at least one lesion that has not previously been irradiatedand for which palliative radiation is potentially indicated and could be safely delivered at the radiation doses specified in this protocol. This lesion must not be within the CNS (brain or spinal cord)
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female premenopausal patients is required
  • Body weight > 30 kg
  • Patients who have had chemotherapy, biologic therapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study are ineligible
  • Receipt of prior radiotherapy or condition for any reason that would contribute radiation dose that would exceed tolerance of normal tissues, could be ineligible, at the discretion of the treating physician
  • Patients who are receiving any other investigational agents
  • Patients with untreated brain metastases, spinal cord compression, or leptomeningeal carcinomatosis should be excluded from this clinical trial
  • Prior exposure to immune-mediated therapy, except for anti-PD-1 or anti_PD-L1 therapy in NSCLC patients are ineligible
  • Pregnant women are excluded from this study
  • HIV-positive patients are ineligible due to the risks associated with immune checkpoint blockade
  • Patients receiving any concurrent chemotherapy, immune therapy, biologic, hormonal therapy for cancer treatment are ineligible
  • Patients with a history of allogeneic organ transplantation are ineligible
  • Patients with active or prior documented autoimmune or inflammatory disorders are ineligible
  • Patients with a history of active primary immunodeficiency are ineligible
  • Patients with a known history of previous clinical diagnosis of tuberculosis are ineligible
  • Patients with an active infection including hepatitis B (known positive HBV surface antigen (HBsAg) result or, hepatitis C are ineligible

Applicable Disease Sites Colon and Rectum; Lung

Therapies Involved Immunotherapy; Radiotherapy

Drugs Involved Durvalumab; Tremelimumab (CP-675,206)

Status Open

Participating Institutions UW Hospital and Clinics