Vismodegib + Atezolizumab for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Ronald Buckanovich
Must not be taking: Antibiotics, Immunosuppressants, Immunostimulants, others
Disqualifiers: Autoimmune disease, Cardiovascular disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like systemic immunosuppressive medications and systemic immunostimulatory agents must be stopped before starting the trial. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination Vismodegib and Atezolizumab for ovarian cancer?
Atezolizumab has shown antitumor activity in ovarian cancer, and combining it with other treatments has enhanced anticancer effects in several cancers. Additionally, a case study reported a positive response to atezolizumab in a patient with a specific type of ovarian cancer.
12345Is the combination of Vismodegib and Atezolizumab safe for humans?
Vismodegib has been approved for use in basal cell carcinoma and is generally considered safe, but it can cause side effects like muscle spasms, hair loss, and nausea. It is also known to cause birth defects, so it should not be used during pregnancy. Atezolizumab, used in other cancers, has its own safety profile, but specific safety data for the combination with Vismodegib in ovarian cancer is not provided.
678910How is the drug combination of Vismodegib and Atezolizumab unique for treating ovarian cancer?
The combination of Vismodegib and Atezolizumab is unique because it targets both the Hedgehog signaling pathway (through Vismodegib) and the immune checkpoint pathway (through Atezolizumab), potentially offering a novel approach to enhance the body's immune response against ovarian cancer, which has limited treatment options beyond traditional chemotherapy.
123411Eligibility Criteria
This trial is for adults with ovarian, fallopian tube, or primary peritoneal cancer that's resistant to platinum-based chemotherapy. Participants need good organ function and blood work within normal ranges, no severe infections or heart issues recently, not on certain medications, and must agree to contraception if applicable. They should have a life expectancy of at least 3 months and an ECOG Performance Status of 0-1.Inclusion Criteria
Negative HIV test at screening
Ability to comply with the study protocol, in the investigator's judgment
My blood and organs are functioning well.
+10 more
Exclusion Criteria
Active or history of autoimmune disease or immune deficiency
I am currently on medication for hepatitis B.
I have not received a live vaccine in the last 4 weeks.
+22 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a combination of vismodegib and atezolizumab. Vismodegib is administered at a fixed dose of 150 mg PO daily, and Atezolizumab is administered at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
Up to 36 months
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of objective response rate, progression-free survival, and overall survival.
Up to 36 months
Participant Groups
The trial tests a combination treatment using Vismodegib and Atezolizumab in patients whose cancer hasn't responded well to platinum-based treatments. The goal is to see if this new approach can improve outcomes since current response rates are low with existing therapies.
1Treatment groups
Experimental Treatment
Group I: vismodegib + atezolizumabExperimental Treatment2 Interventions
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)
Atezolizumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
🇪🇺 Approved in European Union as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UPMC Hillman Cancer CenterPittsburgh, PA
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Who Is Running the Clinical Trial?
Ronald BuckanovichLead Sponsor
Genentech, Inc.Industry Sponsor
References
Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. [2021]Atezolizumab has shown antitumor activity in patients with ovarian cancer. Dual blockade of programmed death-ligand 1 (PD-L1) and VEGF enhances anticancer immunity and augments antitumor activity in several cancers. The safety and efficacy of atezolizumab plus bevacizumab were evaluated in patients with ovarian cancer.
Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. [2023]To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial.
Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers. [2019]Patients with advanced/recurrent epithelial ovarian and uterine cancers have limited treatment options beyond platinum chemotherapy. Both tumor types can express programmed death-ligand 1 (PD-L1), providing a potential therapeutic target for these patients. Here we present data from the ovarian and uterine cancer cohorts of the Phase I atezolizumab monotherapy study (PCD4989g).
Dramatic response to single-agent atezolizumab in a patient with MSI-H serous ovarian cancer. [2022]Patients with ovarian cancer have not benefited substantially from immunotherapy. We report a case of ovarian cancer, however, that responded well to the programmed cell death-ligand 1 inhibitor atezolizumab.
Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer. [2023]To determine the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer.
U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma. [2022]The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies.
Vismodegib (erivedge) for advanced Basal cell carcinoma. [2023]Vismodegib (Erivedge) for advanced basal cell carcinoma.
Vismodegib (ERIVEDGE) pregnancy prevention programme: assessment of risk awareness. [2022]Vismodegib (Erivedge; Roche), a Hedgehog pathway inhibitor (HPI), is indicated for the treatment of symptomatic metastatic basal cell carcinoma (BCC) and locally advanced BCC inappropriate for surgery or radiotherapy. Due to the known risk of HPI teratogenicity, the Erivedge Pregnancy Prevention Program (PPP) was introduced at approval (2013) as part of the EU Risk Management Plan.
Vismodegib: a promising drug in the treatment of basal cell carcinomas. [2012]Hedgehog pathway signaling is important for embryonic development; however, inappropriate reactivation of this pathway in adults has been linked to several forms of cancer. Vismodegib (Erivedge™), a first-in-class hedgehog pathway inhibitor, blocks the pathway by inhibiting the activity of the signaling protein SMO. Preclinical studies have provided promising indications of potential tumor-reducing activity in several cancers. Thus far, clinical pharmacology and Phase I studies have demonstrated the unique pharmacokinetic profile of vismodegib, its efficacy in certain types of tumors and a generally tolerable adverse-event profile. A pivotal Phase II clinical trial confirmed the favorable benefit:risk profile of vismodegib in advanced basal cell carcinoma.
A phase II, randomized, placebo-controlled study of vismodegib as maintenance therapy in patients with ovarian cancer in second or third complete remission. [2015]Hedgehog pathway inhibition has been suggested as a potential maintenance treatment approach in ovarian cancer through disruption of tumor-stromal interactions. Vismodegib is an orally available Hedgehog pathway inhibitor with clinical activity in advanced basal cell carcinoma and medulloblastoma. This phase II, randomized, double-blind, placebo-controlled trial was designed to provide a preliminary estimate of efficacy in patients with ovarian cancer in second or third complete remission (CR).
Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer. [2022]Vigil® is a personalized vaccine that enhances tumor neoantigen expression. We investigated for the first time safety and efficacy of Vigil in combination with atezolizumab in relapsed ovarian cancer (OC) patients. This is a randomized, Phase 1 study of Vigil, an autologous tumor tissue transfected vaccine encoding for GMCSF and bi-shRNA-furin thereby creating enhanced immune activation and TGFβ expression control. Part 1 is a safety assessment of Vigil (1 × 10e7 cells/mL/21 days) plus atezolizumab (1200 mg/21 days). Part 2 is a randomized study of Vigil first (Vigil-1st) or atezolizumab first (Atezo-1st) for two cycles followed by the combination of both agents. The primary endpoint of the study was the determination of safety. Twenty-four patients were enrolled in the study; three patients to Part 1 and 21 to Part 2. Patients in Part 1 completed combination therapy without dose-limiting toxicity justifying expansion to Part 2. Twenty-one patients were randomized (1:1) to Part 2 to Vigil-1st (n = 11) or Atezo-1st (n = 10). Grade 3/4 treatment-related adverse events of Atezo-1st vs. Vigil-1st were 17.2% vs. 5.1%. Median overall survival (OS) was not reached (NR) (Vigil-1st) vs. 10.8 months (Atezo-1st) (hazard ratio [HR] 0.33). The exploratory subset analysis of BRCAwt suggested improved OS benefit [NR in Vigil-1st vs. 5.2 months in Atezo-1st, HR 0.16, p 0.027]. The Vigil-1st combination therapy with atezolizumab was safe and results in support continued investigation in BRCAwt patients.