What side effects are associated with this type of intervention?

Gorlin Syndrome, also known as Basal Cell Nevus Syndrome, is often treated with Hedgehog pathway inhibitors like ENV-101 (Taladegib). Common side effects of Hedgehog pathway inhibitors include muscle spasms, hair loss, altered taste, weight loss, fatigue, nausea, and decreased appetite. Additionally, treatments like imiquimod cream, used for basal cell carcinoma, can cause local skin reactions such as redness, swelling, and vitiligo-like depigmentation. It is important for patients to discuss these potential side effects with their healthcare provider to manage them effectively.

What prior FDA approvals exist?

The FDA has approved Hedgehog Pathway Inhibitors for the treatment of Gorlin Syndrome, also known as Basal Cell Nevus Syndrome. Vismodegib (Erivedge) was the first such drug approved in 2012, followed by Sonidegib (Odomzo) in 2015. These drugs inhibit the Hedgehog signaling pathway, which is crucial in the pathogenesis of Gorlin Syndrome. Both drugs are used to treat advanced basal cell carcinoma, a common manifestation of Gorlin Syndrome.

What other types of research exist?

Promising alternatives to ENV-101 for Gorlin Syndrome patients include vismodegib and sonidegib, both of which are Hedgehog pathway inhibitors. Vismodegib has been used successfully to shrink keratocystic odontogenic tumors in patients with basal cell nevus syndrome. Additionally, ongoing research and clinical trials may introduce new therapies targeting the Hedgehog pathway or other molecular targets relevant to Gorlin Syndrome by 2024.

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Hedgehog Pathway Inhibitor

Taladegib for Advanced Cancer

Phase 2

Waitlist Available

Research Sponsored by Endeavor Biomedicines, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has histologically or cytologically confirmed solid tumor that harbors a PTCH1 loss of function mutation, identified via genomic sequencing routinely performed at a CLIA certified laboratory

Able to take medication orally

Must not have

Females and males that are unwilling to refrain from blood or blood product donation for the duration of the study and for 30 days after their final study dose

Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to study start

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ENV-101, a new drug, in patients with advanced cancers that have specific genetic mutations and haven't responded to other treatments. The drug works by blocking a signal that tells cancer cells to grow.

Who is the study for?

Adults with advanced solid tumors that have a specific genetic change (PTCH1 loss of function mutation) can join this trial. They must be able to take pills, have a life expectancy over 3 months, and not respond to standard treatments or refuse them. People who are pregnant, nursing, or unwilling to use birth control; those with severe allergies to ENV-101 components; active infections like HIV/HBV/HCV; serious heart conditions; recent major surgeries; other cancers within the last 5 years; or uncontrolled autoimmune diseases cannot participate.

What is being tested?

The trial is testing ENV-101 (taladegib), which blocks a cancer growth pathway in patients whose tumors no longer respond to usual treatments. It's done in two stages: first, finding the right dose by trying two different amounts on about 44 people. Then possibly expanding the group based on these results.

What are the potential side effects?

Possible side effects of taladegib may include digestive issues due to its oral intake nature, allergic reactions for those sensitive to its ingredients, and potential impacts on liver function as it interacts with certain enzymes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My tumor has a PTCH1 mutation, confirmed by a certified lab test.

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I can take medicine by mouth.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I agree not to donate blood during and for 30 days after the study.

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I haven't been part of any clinical study or taken experimental drugs in the last 28 days.

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I haven't had major surgery in the last 28 days and don't expect to need one during the study.

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I am willing to use birth control during the study and for 3 months after.

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I am not pregnant or nursing.

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I don't have severe nausea, vomiting, malabsorption issues, or significant bowel surgery that would affect medication absorption.

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I haven't taken strong medication that affects liver enzymes in the last 12 days.

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I do not have an active infection or confirmed HIV, HBV, or HCV at the start of the study.

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I am not currently receiving any cancer treatments other than what this study provides.

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I agree not to donate sperm/eggs during and for 3 months after the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate (ORR)

Secondary study objectives

Change in Gli1 inhibition

Change in steady-state exposure to study medication

Clinical Benefit Rate (CBR)

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: 300 mg ENV-101Experimental Treatment1 Intervention

ENV-101 (taladegib) tablets, 300 mg once-daily in 28-day cycles

Group II: 200 mg ENV-101Experimental Treatment1 Intervention

ENV-101 (taladegib) tablets, 200 mg once-daily in 28-day cycles

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Gorlin Syndrome treatments often target the Hedgehog (Hh) signaling pathway, which is disrupted due to PTCH1 gene mutations. ENV-101 (Taladegib) is a Hedgehog pathway inhibitor under study for its potential to inhibit abnormal cell growth in these patients. Other treatments include topical agents like 5-fluorouracil and tretinoin, which help prevent new tumors and inhibit existing ones, and photodynamic therapy (PDT) with methyl aminolevulinate, which reduces the need for surgical procedures. These treatments are crucial as they offer non-surgical options to manage the multiple basal cell carcinomas characteristic of Gorlin Syndrome.

Long-term management of basal cell nevus syndrome with topical tretinoin and 5-fluorouracil.Basal cell nevus syndrome. Unresponsiveness of early cutaneous lesions to topical 5-fluorouracil or dinitrochlorobenzene.Treatment of facial actinic keratoses with aminolevulinic acid photodynamic therapy (ALA-PDT) or ingenol mebutate 0.015% gel with and without prior treatment with ALA-PDT.