What side effects are associated with this type of intervention?

Common treatments for Neuroendocrine Tumors (NETs) include mTOR inhibitors like everolimus and sirolimus, and somatostatin analogs such as octreotide and lanreotide. mTOR inhibitors can cause side effects including stomatitis, rash, diarrhea, fatigue, infections, and hyperglycemia. Somatostatin analogs may lead to gastrointestinal disturbances, gallstones, and glucose metabolism disorders. Pasireotide, another somatostatin analog, has a higher incidence of hyperglycemia and diabetes mellitus, making it less commonly used.

What prior FDA approvals exist?

Everolimus, an mTOR inhibitor, has been approved by the FDA for the treatment of advanced neuroendocrine tumors of pancreatic origin (PNET), gastrointestinal origin (GI-NET), and lung origin. It works by inhibiting the mTOR pathway, which is involved in cell growth and proliferation. Other related drugs include sunitinib, which targets multiple tyrosine kinases and is approved for advanced PNET. These treatments aim to control tumor growth and progression in patients with NETs.

What other types of research exist?

Promising alternatives to nab-sirolimus for NETs include: 1) Everolimus, another mTOR inhibitor, which has shown efficacy in various NETs. 2) Peptide Receptor Radionuclide Therapy (PRRT) with lutetium Lu-177 dotatate for somatostatin receptor-positive tumors. 3) Cabozantinib, a tyrosine kinase inhibitor, which has demonstrated activity in medullary thyroid cancer and may be applicable to NETs. 4) Surufatinib, a small molecule tyrosine kinase inhibitor, which has shown promise in advanced extrapancreatic NETs.

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mTOR Inhibitor

Nab-Sirolimus for Neuroendocrine Tumors

Phase 2

Recruiting

Research Sponsored by Aadi Bioscience, Inc.

Eligibility Criteria Checklist

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

Must have

Minimum of 4 weeks since any major surgery, completion of radiation, and adequately recovered from the acute toxicities of any prior therapy, including neuropathy, to Grade ≤1

Adequate renal function: creatinine clearance ≥30 mL/min

Must not have

Patients with inactivating TSC1 or TSC2 alterations (based on tissue or liquid NGS)

Patients who have any severe and/or uncontrolled medical or psychiatric conditions or other conditions that could affect their participation including known or suspected brain metastases, severe heart disease, severe lung disease, nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy, a history of malignancies other than the one under treatment unless the patient is disease-free for more than 5 years from diagnosis, uncontrolled hypertension, history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension, active Hepatitis B and/or Hepatitis C infection and detectable viral load despite antiviral therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests nab-sirolimus, a drug that targets tumors, in patients with advanced neuroendocrine tumors of the GI tract, lung, or pancreas. The drug works by blocking a protein that helps tumor cells grow and survive. Nab-sirolimus is the first agent specifically approved for advanced unresectable or metastatic malignant PEComa.

Who is the study for?

This trial is for adults with well-differentiated neuroendocrine tumors in the GI tract, lung, or pancreas. They should not have had prior mTOR inhibitor treatment and can have up to two other therapies (excluding somatostatin analogs). Participants need functioning major organs, controlled HIV if present, no severe medical conditions or recent surgeries, and must use effective contraception.

What is being tested?

The study tests nab-sirolimus on patients who haven't used mTOR inhibitors before. It's a Phase 2 trial where all participants receive the same drug to see how it affects their cancer. The focus is on those with specific types of NETs that are advanced and cannot be surgically removed.

What are the potential side effects?

While side effects specific to nab-sirolimus aren't listed here, common ones for similar drugs include mouth sores, skin issues like rash or acneiform dermatitis, fatigue, increased risk of infections due to immune suppression, high blood sugar levels, and possible lung problems.

Eligibility Criteria

Inclusion Criteria

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

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It's been over 4 weeks since my last major surgery or radiation, and I've recovered from severe side effects.

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My kidneys work well enough (creatinine clearance ≥30 mL/min).

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I have HIV but no AIDS-related infections in the last year, my viral load is under control, and I'm not on strong CYP3A4 drugs.

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My blood counts meet the required levels for treatment.

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I am fully active or able to carry out light work.

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I am 18 years old or older.

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I have a specific type of cancer in my GI tract, lung, or pancreas and have had 2 or fewer treatments.

Exclusion Criteria

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

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My tests show TSC1 or TSC2 gene changes.

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I do not have severe health issues that could affect my participation in the study.

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I have a functional neuroendocrine tumor causing uncontrollable symptoms.

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I have previously been treated with mTOR inhibitors like nab-sirolimus.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 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

Efficacy of nab-sirolimus

Secondary study objectives

Disease control rate

Duration of response

Incidence and severity of treatment

+3 more

Side effects data

From 2022 Phase 1 & 2 trial • 60 Patients • NCT03439462

67%

Mucositis

58%

Fatigue

43%

Rash

38%

Diarrhea

37%

Myelosuppression (Thrombocytopenia)

35%

Nausea

30%

Myelossupression (Neutropenia)

28%

Hypertriglyceridemia

27%

Weight decreased

27%

Myelosuppression (Anemia)

25%

Decreased appetite

22%

Mucosal inflammation

18%

Lipase increased

18%

Dermatitis

18%

Hypokalemia

18%

Vomiting

17%

Epistaxis

17%

Dysgeusia

15%

Hyperglycemia

13%

Amylase increased

12%

Abdominal pain

12%

Hypercholesterolemia

10%

Headache

10%

Infection

10%

Hypophosphataemia

ALT

Dry mouth

Anal inflammation

AST

Candida infection

Hypoalbuminaemia

Proctalgia

Dehydration

Nail disorder

Dizziness

Application site pain

Proteinuria

Alopecia

Anorexia

Gastrooesophageal reflux disease

Oedema peripheral

Dry eye

Hypertension

Hypomagnesaemia

Dry skin

Taste disorder

Pneumonia

Colitis

Enterocolitis infectious

Rectal perforation

Stomatitis

100%

80%

60%

40%

20%

Study treatment Arm

Total

Cohort 1: Nab-Sirolimus 30 mg/m2 qw3/4

Cohort 2 Nab-Sirolimus 20 mg/m2 qw3/4

Cohort 3: Nab-Sirolimus 20 mg/m2 qw2/4

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: neuroendocrine tumorsExperimental Treatment1 Intervention

Patients with well-differentiated neuroendocrine tumors of the gastrointestinal tract, lung, or pancreas.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

nab-sirolimus

2017

Completed Phase 2

~140

0 / 11Eligibility 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

The most common treatments for Neuroendocrine Tumors (NETs) include mTOR inhibitors, somatostatin analogs, and targeted therapies. mTOR inhibitors, such as nab-sirolimus, work by blocking the mTOR pathway, which is crucial for cell growth and proliferation, thereby slowing tumor growth. Somatostatin analogs, like octreotide and lanreotide, inhibit hormone secretion and can control symptoms related to hormone hypersecretion. Targeted therapies, such as tyrosine kinase inhibitors, block specific molecules involved in tumor growth and angiogenesis. These treatments are vital for NET patients as they offer options to manage tumor growth, control symptoms, and improve quality of life.

Molecular target therapy for gastroenteropancreatic endocrine tumours: biological rationale and clinical perspectives.