What side effects are associated with this type of intervention?

The most common treatments for Leiomyosarcoma in the trial include Durvalumab, Olaparib, and Cediranib. Durvalumab, a PD-L1 inhibitor, can cause side effects such as fatigue, decreased appetite, and immune-related adverse events like pneumonitis and colitis. Olaparib, a PARP inhibitor, is associated with nausea, fatigue, anemia, and vomiting. Cediranib, a VEGFR inhibitor, commonly leads to hypertension, diarrhea, and fatigue. These side effects are important considerations for patients and doctors when evaluating treatment options.

What prior FDA approvals exist?

For the treatment of Leiomyosarcoma, the FDA has approved several drugs, though not all are directly similar to Durvalumab, Olaparib, or Cediranib. Pembrolizumab, a PD-1 inhibitor, has shown potential benefits in soft tissue sarcomas with high microsatellite instability, which may include some cases of LMS. However, PARP inhibitors like Olaparib have not shown significant efficacy in LMS and are not FDA-approved for this indication. VEGFR inhibitors such as Pazopanib have been approved for the treatment of advanced soft tissue sarcomas, including LMS, demonstrating efficacy in delaying disease progression.

What other types of research exist?

Promising novel alternatives for Leiomyosarcoma patients include: <ol> <li>Pembrolizumab (PD-1 Inhibitor) combined with Lenvatinib (Tyrosine Kinase Inhibitor), which has shown improvements in progression-free survival and overall survival in proficient MMR tumors.</li> <li></li> </ol> Regorafenib, which has demonstrated improved progression-free survival in various subtypes of soft tissue sarcomas, including LMS. 3. Axitinib (VEGFR Inhibitor) combined with Pembrolizumab, which has shown clinical activity in advanced sarcomas. 4. Nivolumab (PD-1 Inhibitor) with or without Ipilimumab (CTLA-4 Inhibitor), which has been evaluated in metastatic sarcoma trials. These alternatives offer different mechanisms of action and may provide additional options for LMS patients.

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Angiogenesis Inhibitor

Combination Therapy with Cediranib, Olaparib, and Durvalumab for Advanced Solid Tumors (DAPPER Trial)

Phase 2

Waitlist Available

Led By Lillian Siu, MD

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of medicines to help the immune system fight advanced colorectal, pancreatic, and soft tissue cancers. It aims to see if these new treatments can be more effective for patients whose cancers are hard to treat with standard therapies.

Who is the study for?

Adults with advanced colorectal cancer, pancreatic adenocarcinoma, or leiomyosarcoma that's not curable and has failed standard therapy can join. They must be willing to use effective contraception, provide tumor tissue samples, have normal organ function, and no recent major surgeries. Excluded are those with certain heart conditions, uncontrolled hypertension or seizures, recent bleeding events or blood transfusions.

What is being tested?

The trial tests combinations of Olaparib (a pill for DNA repair inhibition), Cediranib (a pill for blocking blood vessel growth in tumors), and Durvalumab (an IV drug boosting immune response against cancer). Participants will receive treatments based on their assigned cohort to see how these drugs affect tumor biomarkers.

What are the potential side effects?

Possible side effects include fatigue, nausea, diarrhea from Olaparib; high blood pressure and fatigue from Cediranib; infusion reactions like fever or chills and autoimmune-like symptoms such as skin rash or thyroid issues from Durvalumab.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Changes in genomic and immune biomarkers that will be measured in the baseline biopsy and the first on-treatment biopsy by applying a log-transformation and the t-test.

Side effects data

From 2022 Phase 2 trial • 80 Patients • NCT03015129

65%

Fatigue

63%

Abdominal pain

55%

Diarrhea

43%

Pain

40%

Weight loss

35%

Hypertension

30%

Anorexia

30%

Constipation

28%

Nausea

28%

Pruritus

25%

Vomiting

20%

Dyspnea

20%

Urinary tract infection

18%

Rash maculo-papular

15%

Cough

15%

Abdominal Pain

15%

Back pain

15%

Increased Urinary Frequency

15%

Weight gain

13%

Arthralgia

10%

Dizziness

10%

Anxiety

10%

Bladder infection

10%

Nasal congestion

10%

Vaginal discharge

Colitis

Dry mouth

Dry skin

Fever

Anal pain

Edema limbs

Flatulence

Headache

Hot flashes

Myalgia

Small intestinal obstruction

Thromboembolic event

Urinary frequency

Urinary tract pain

Confusion

Renal and urinary disorders - Other, specify

Adrenal insufficiency

Anemia

Ascites

Gastroesophageal reflux disease

Hypomagnesemia

Lymphedema

Memory impairment

Mucositis oral

Pneumonitis

Rash acneiform

Sinus bradycardia

Upper respiratory infection

Urinary urgency

Vaginal hemorrhage

Alanine aminotransferase increased

Aspartate aminotransferase increased

Alkaline phosphatase increased

Colonic perforation

Dysarthria

Blood bilirubin increased

CPK increased

Creatinine increased

Myositis

Rectal hemorrhage

Hypothyroidism

Left ventricular systolic dysfunction

Lethargy

Muscle weakness left-sided

Myocarditis

Rectal pain

Weight Loss

Fall

Generalized muscle weakness

Hyperglycemia

Hyperkalemia

Pain in extremity

Peripheral sensory neuropathy

Pleural effusion

Skin infection

100%

80%

60%

40%

20%

Study treatment Arm

Durvalubmab

Durvalubmab + Tremelimumab

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: Cohort BExperimental Treatment2 Interventions

Cediranib (given orally at a dose of 20 mg daily, 5 days on 2 days off) in combination with Durvalumab (given intravenously at a dose of 1500 mg every 4 weeks)

Group II: Cohort AExperimental Treatment2 Interventions

Olaparib (given orally at a dose of 300 mg twice a day) in combination with Durvalumab (given intravenously at a dose of 1500 mg every 4 weeks)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olaparib

2007

Completed Phase 4

~2190

Cediranib

2016

Completed Phase 3

~4030

Durvalumab

2017

Completed Phase 2

~3750

Do I qualify?Apply below to find out

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

Leiomyosarcoma (LMS) treatments often target specific pathways to inhibit tumor growth and spread. Durvalumab, a PD-L1 inhibitor, works by blocking the PD-L1 protein on cancer cells, enhancing the immune system's ability to detect and destroy these cells. Olaparib, a PARP inhibitor, prevents cancer cells from repairing their DNA, leading to cell death, particularly in cells with existing DNA repair deficiencies. Cediranib, a VEGFR inhibitor, blocks vascular endothelial growth factor receptors, reducing blood supply to the tumor and inhibiting its growth. These mechanisms are crucial for LMS patients as they offer targeted approaches to disrupt cancer cell survival and proliferation, potentially improving treatment outcomes.

Integrating Precision Medicine into the Contemporary Management of Gynecologic Cancers.PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.The safety of antiangiogenic agents and PARP inhibitors in platinum-sensitive recurrent ovarian cancer.