NCT03802747

Withdrawn

Phase 1

Phase I Study of Dual Immune Checkpoint Blockade (Anti-PD-L1 (Durvalumab) (MEDI4736) and Anti-CTLA4 (Tremelimumab) Plus Yttrium-90 (Y-90) Radioembolization & Stereotactic Body Radiation Therapy (SBRT) in Refractory Metastatic MSS (Microsatellite Stable) Colorectal Cancer With Liver Metastases

University of Colorado, Denver0 sitesAugust 2019

InterventionsDurvalumab Y-90 Selective Internal Radiation Therapy (SIRT)Stereotactic Body Radiation Therapy (SBRT)Durvalumab and Tremelimumab

DrugsDurvalumab Durvalumab and Tremelimumab Y-90 Selective Internal Radiation Therapy (SIRT)Stereotactic Body Radiation Therapy (SBRT)

Overview

Phase: Phase 1
Intervention: Durvalumab
Conditions: Colorectal Cancer
Sponsor: University of Colorado, Denver
Primary Endpoint: Incidence of Treatment Related Adverse Events
Status: Withdrawn
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This study is evaluating the combination of Y-90 radioembolization followed by SBRT with the immunotherapy drugs, durvalumab and tremelimumab, to improve disease control of liver metastases for patients with microsatellite stable colorectal cancer.

Registry

clinicaltrials.gov

Start Date

August 2019

End Date

December 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Colorado, Denver

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologic or cytologic confirmation of metastatic microsatellite stable colorectal cancer
•Liver metastases not amenable to resection for which palliative Y-90 and SBRT is considered appropriate standard therapy
•Patients should have received at least one prior standard therapy for metastatic disease. Prior therapies should include regimens containing oxaliplatin and irinotecan in combination with a fluoropyrimidine if appropriate (e.g., FOLFOX and FOLFIRI or their variants) unless contraindicated, not tolerated, or declined.
•Male or female, age 18 or older
•ECOG performance status of 0 or 1
•Body weight \>30 kg
•Life expectancy of greater than 6 months
•Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
•Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
•Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

Exclusion Criteria

•Participation in another clinical study with an investigational drug during the last 4 weeks.
•Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
•Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
•Patients with Grade \>2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
•Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
•Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
•Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
•History of allogenic organ transplantation.
•Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
•Patients with vitiligo or alopecia

Arms & Interventions

Y-90, SBRT, and Durvalumab Alone

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab.

Intervention: Durvalumab

Y-90, SBRT, and Durvalumab Alone

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab.

Intervention: Y-90 Selective Internal Radiation Therapy (SIRT)

Y-90, SBRT, and Durvalumab Alone

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab.

Intervention: Stereotactic Body Radiation Therapy (SBRT)

Y-90, SBRT, and Durvalumab + Tremelimumab

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab + Tremelimumab.

Intervention: Durvalumab and Tremelimumab

Y-90, SBRT, and Durvalumab + Tremelimumab

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab + Tremelimumab.

Intervention: Y-90 Selective Internal Radiation Therapy (SIRT)

Y-90, SBRT, and Durvalumab + Tremelimumab

Six patients will be enrolled in cohorts of three to be administered Y-90, SBRT, and Druvalumab + Tremelimumab.

Intervention: Stereotactic Body Radiation Therapy (SBRT)

Outcomes

Primary Outcomes

Incidence of Treatment Related Adverse Events

Time Frame: Start of study to 3 months post treatment completion, up to 5 years

Adverse events related to Y-90, SBRT, and durvalumab plus tremelimumab will be summarized by dose and severity as assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.

Dose-Limiting Toxicity of Y-90+SBRT in Combination with Dual Immune Checkpoint Blockade

Time Frame: Start of study to 3 months post treatment completion, up to 5 years

Defined as the rate of \>Grade 3 treatment-related adverse events during treatment or within 3 months of treatment completion.

Secondary Outcomes

Duration of Response (DoR)(Landmark time of initiation of tremelimumab, about 18 weeks after the start of treatment, to end of follow up, up to 2 years)
Progression Free Survival for Three Months (PFS)(Landmark time of initiation of tremelimumab, about 18 weeks after the start of treatment, to end of follow up, up to 2 years)
Overall Response Rate (ORR)(Landmark time of initiation of tremelimumab, about 18 weeks after the start of treatment, to end of follow up, up to 2 years)
Overall Survival for Two Years (OS)(Landmark time of initiation of tremelimumab, about 18 weeks after the start of treatment, to end of follow up, up to 2 years)
Liver Progression Free Survival for One Year (L-PFS)(Landmark time of initiation of tremelimumab, about 18 weeks after the start of treatment, to end of follow up, up to 2 years)
Pathological Response Rates (PRR)(Landmark time of initiation of tremelimumab, about 18 weeks after the start of treatment, to end of follow up, up to 2 years)
Time to Tumor Progression (TTP)(Landmark time of initiation of tremelimumab, about 18 weeks after the start of treatment, to end of follow up, up to 2 years)