Vismodegib Combined With Atezolizumab in Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

NCT05538091 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 22-017
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will treat patients with platinum resistant ovarian, fallopian tube or primary peritoneal cancer as defined by a progression free interval within six months of completion of most recent platinum-based treatment with a combination of vismodegib and atezolizumab. Despite recent improvements in treatment of ovarian cancer with the introduction of PARP inhibitors, response rates to therapy in the platinum resistant setting remain dismal with response rates of only 10-20% reported for single agent cytotoxic therapies. Given the poor prognosis and limited treatment options for these patients, this population is considered appropriate for trials of novel therapeutic candidates.

Conditions

Platinum-Resistant Fallopian Tube Carcinoma; Platinum-Resistant Primary Peritoneal Carcinoma; PARP Inhibitor; Hedgehog Inhibitor

Outcome Measures

Primary Outcomes (2)

• Safety Determined by Dose Limiting Toxicities (DLTs)

  Immune-related and other adverse events and/or serious adverse events related to treatment occurring within the first two cycles of treatment that require a dose reduction (Dose Limiting Toxicities (DLTs)). All adverse events will be tabulated by Type, Grade, Relatedness to Treatment and Expectedness, Cycle of Treatment, and by Dose Administered.

  Up to two weeks

• Objective Response Rate (ORR)

  Confirmed complete response or partial response by RECIST 1.1. Per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 36 months

Secondary Outcomes (4)

• Immune-modified Response Rate by imRECIST

  Up to 36 months

• Modified Response Rate by iRECIST

  Up to 36 months

• Overall Survival (OS)

  Up to 36 months

• Progression-free survival (PFS)

  Up to 36 months

Study Arms (1)

vismodegib + atezolizumab

EXPERIMENTAL

Vismodegib: fixed dose of 150 mg PO daily Atezolizumab: fixed dose of 1200 mg Q3W (1200 mg on Day 1 of each 21-day cycle)

Drug: Vismodegib; Drug: Atezolizumab

Interventions

Vismodegib DRUG

A small-molecule SMO inhibitor designed to specifically target the hedgehog pathway, a known driver of BCC. It systemically inhibits hedgehog pathway signaling. Following mutation, SMO is released from the inhibitory effect of PTCH and moves to the cell surface, activating GLI. GLI travels to the nucleus and initiates transcription of target genes that regulate basal cell growth and proliferation.

Also known as: ERIVEDGE

vismodegib + atezolizumab

Atezolizumab DRUG

Atezolizumab is a humanized monoclonal antibody immune checkpoint inhibitor that selectively binds to PD-L1 to stop the interaction between PD-1 and B7.1 (CD80 receptors). The antibody still allows interaction between PD-L2 and PD-1.

Also known as: Tecentriq

vismodegib + atezolizumab

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form
• Ability to comply with the study protocol, in the investigator's judgment
• Histologically or cytologically confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer
• Platinum status, defined by disease progression during or following treatment with platinum-based chemotherapy within 6 months of completing therapy
• Measurable or non-measurable but evaluable disease per RECIST v1.1 {Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.}
• Availability of a representative tumor specimen for exploratory biomarker research will be required for 12 patients (see Section 5.4.5 for information on tumor specimens)
• ECOG Performance Status of 0-1
• Life expectancy ≥ 3 months
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: ANC ≥ 1.5 ⋅ 109/L (1500/μL) without granulocyte colony-stimulating factor support; Lymphocyte count ≥ 0.5 ⋅ 109/L (500/μL); Platelet count ≥ 100 ⋅ 109/L (100,000/μL) without transfusion; Hemoglobin ≥ 80 g/L (8 g/dL) (Patients may be transfused to meet this criterion.)
• AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 ⋅ upper limit of normal (ULN), with the following exceptions:
• Patients with documented liver metastases: AST and ALT ≤ 5 ⋅ ULN
• Patients with documented liver or bone metastases: ALP ≤ 5 ⋅ ULN
• Serum bilirubin ≤ 1.5 ⋅ ULN with the following exception:
• Patients with known Gilbert disease: serum bilirubin ≤ 3 ⋅ ULN
• Serum creatinine ≤ 1.5 ⋅ ULN

You may not qualify if:

• Inability or unwillingness to swallow capsules
• Inability or unwillingness to comply with study procedures
• History of leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• o Patients with indwelling catheters (e.g., PleurX→) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix 9) for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted).
• Active tuberculosis

Sponsors & Collaborators

• Ronald Buckanovich: lead
• Genentech, Inc.: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Interventions

HhAntag691; atezolizumab

Study Officials

• Ronald J Buckanovich, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelsey Mitch, BSN

CONTACT

412-641-2357; adamikka2@upmc.edu

Lucia Borasso, BSN

CONTACT

412-641-3304; borrlm@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 8, 2022
• First Posted: September 13, 2022
• Study Start: May 15, 2023
• Primary Completion (Estimated): March 17, 2031
• Study Completion (Estimated): March 17, 2033
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)