Anti-PD-L1 and SAbR for Ovarian Cancer

NCT03312114 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: STU 032017-078
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Programmed death-1 receptor ligand (PD-L1) the ligand for PD-1 is a key therapeutic target in the reactivation of the immune response against multiple cancers. Pharmacologic inhibitors of PD-1 have also demonstrated significant anti-tumor activity and are currently under active clinical exploration. avelumab (MSB0010718C; anti-PD-L1 is a fully human anti-PD-L1 igG1 antibody that has shown promising efficacy and an acceptable safety profile in multiple tumor types. Radiation therapy (RT) is one of the mainstream treatments of cancer therapy along with surgery and chemotherapy, yet RT is the only treatment that does not leave the patients immunocompromised (unlike chemotherapy) and keeps the dying tumor / antigen depot within the host (unlike surgery), providing an opportunity for antigen presentation. Therefore, RT is a rational choice to combine with immunotherapy for cancer treatment.

Conditions

Recurrent Epithelial Cancer of Ovary; Primary Peritoneal Carcinoma; Fallopian Tube Cancer

Outcome Measures

Primary Outcomes (1)

• To Assess Overall Clinical Response Rates Per RECIST Criteria.

  Analysis of (with safety lead-in) trial of combined Avelumab (MSB0010718C) anti-PD-L1checkpoint blockade with SAbR for Recurrent Ovarian and peritoneal ,fallopian tube cancer (ROPT) is to assess overall clinical response rates per RECIST criteria .

  1 year,4 months

Secondary Outcomes (1)

• Overall Survival

  1 year, 4 months

Study Arms (1)

Single arm

EXPERIMENTAL

Avelumab and SABR

Drug: Avelumab

Interventions

Avelumab DRUG

Avelumab\* (MSB0010718C; anti-PD-L1 is a fully human anti-PD- L1 IgG1 antibody)

Also known as: Bavencio

Single arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female subjects aged ≥ 18 years.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female subjects aged ≥ 18 years.
• Performance ECOG status of 0-2
• Patient is able and willing to comply with protocol and study procedures for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up visits.
• Adequate Physiologic function:
• Hematologic: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused)
• Hepatic: Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
• Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• Pregnancy and contraception:
• Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential.
• Contraception: Women of child-bearing potential and their male partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry.,
• Histologic diagnosis of recurrent epithelial ovarian ,fallopian ,peritoneal cancer
• Patients with platinum sensitive ovarian cancer must have progressed through at least one platinum containing regimen for recurrent disease.
• Patients with platinum resistant ovarian cancer must have progressed through at least one prior chemotherapy regimen for recurrent ovarian cancer.
• Patients must have received at least one prior chemotherapy regimen and up to any number of prior systemic regimens including chemotherapy and molecular targeted therapy other than PD1/ PDL1/ PDL2 inhibitors.
• Metastatic disease of at least two Non-CNS sites (including the index lesion to be treated) measurable by RECIST criteria with at least one site outside of the radiation field and evaluable by RECIST criteria for evaluation of response.

You may not qualify if:

• IMMUNOSUPRESSANTS: "Current use of immunosuppressive medication, EXCEPT for the following: a. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)."
• AUTOIMMUNE DISEASE: "Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible."
• ORGAN TRANSPLANTATION: "Prior organ transplantation including allogenic stem-cell transplantation."
• HIV/AIDS: "Known history of testing positive for HIV or known acquired immunodeficiency syndrome."
• HEPATITIS: "Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)"
• VACCINATION: "Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines "
• HYPERSENSITIIVTY TO STUDY DRUG: "Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)"
• CARDIOVASCULAR DISEASE: "Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication."
• OTHER PERSISTING TOXICITIES: "Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade \> 2); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable."
• Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis ,Severe COPD requiring \> 3 hospitalization in the past year Or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• No concomitant therapy with any of the following: IL2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; or other investigational therapies; all such therapies must have been discontinued \>4weeks prior to registration.
• No active TB,
• Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients must not be pregnant or nursing.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms

Interventions

avelumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Phase II trial of Concurrent Anti-PD-L1 and SAbR for Patients with Persistent or Recurrent Epithelia
• Organization: University of Texas Southwestern Medical Center

kevin.albuquerque@utsouthwestern.edu

(214) 645-7296

Study Officials

• Kevin Albuquerque, MD

  kevin.albuquerque@utsouthwestern.edu

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: October 17, 2017
• Study Start: November 9, 2017
• Primary Completion: March 19, 2019
• Study Completion: March 19, 2019
• Last Updated: November 12, 2020
• Results First Posted: November 12, 2020

Record last verified: 2020-10

Locations

US (1)