What is the mechanism of action of this treatment?

Olaparib, a PARP inhibitor, works by preventing cancer cells from repairing their DNA, leading to cell death. Temozolomide, a chemotherapy drug, damages the DNA of cancer cells, stopping them from dividing and growing. For Pheochromocytoma patients, this combination is significant because it targets the cancer cells' ability to repair and proliferate, potentially reducing tumor growth and improving treatment efficacy.

What side effects are associated with this type of intervention?

The most common side effects of treatments for pheochromocytoma, particularly those similar to Olaparib (a PARP inhibitor) and Temozolomide (a chemotherapy agent), include nausea, fatigue, anemia, and thrombocytopenia. Additionally, Temozolomide may cause vomiting, neutropenia, and general myelosuppression. These side effects reflect the combined impact of both drug classes on the body.

What prior FDA approvals exist?

There is no specific mention of prior FDA approvals for the treatment of pheochromocytoma using Olaparib or Temozolomide in the provided context. However, the phase II trial is investigating the combination of Olaparib, a PARP inhibitor, and Temozolomide, a chemotherapy drug, for treating metastatic or unresectable neuroendocrine cancers, including pheochromocytoma. This suggests that while these drugs are being studied, they may not yet have specific FDA approval for this indication.

What other types of research exist?

As of 2024, promising novel alternatives to Olaparib and Temozolomide for Pheochromocytoma patients include targeted therapies such as tyrosine kinase inhibitors (e.g., Cabozantinib, Vandetanib) and immunotherapies (e.g., Pembrolizumab). These treatments have shown efficacy in other neuroendocrine tumors and may offer new options for Pheochromocytoma patients.

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PARP Inhibitor

Olaparib + Temozolomide for Neuroendocrine Cancer

Phase 2

Recruiting

Led By Jaydira Del Rivero

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

No prior treatment with temozolomide, dacarbazine, or a poly ADP ribose polymerase (PARP) inhibitor

No history of myelodysplastic syndrome (MDS) (or any dysplastic leukocyte morphology suggestive of MDS) or acute myeloid leukemia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomization to the first documentation of disease progression (per response evaluation criteria in solid tumors [recist] version 1.1) or death, assessed up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, olaparib and temozolomide, to treat advanced neuroendocrine cancers that have spread or can't be removed by surgery. Olaparib stops cancer cells from repairing themselves, while temozolomide kills them or stops their growth. The goal is to see if this combination works better than using temozolomide alone. Olaparib has shown activity in ovarian and other solid tumors, while temozolomide has been effective in treating various types of neuroendocrine tumors.

Who is the study for?

Adults with advanced neuroendocrine cancer (pheochromocytoma or paraganglioma) that's spread or can't be surgically removed. Must not have had certain prior treatments, no known allergies to PARP inhibitors, and must agree to contraception. Pregnant/nursing women are excluded.

What is being tested?

The trial is testing if adding Olaparib, a drug that prevents tumor cells from repairing DNA damage, to the usual chemotherapy Temozolomide helps more in treating advanced neuroendocrine cancers than chemotherapy alone.

What are the potential side effects?

Olaparib may cause nausea, fatigue, blood cell count changes leading to infections or bleeding problems, and potential allergic reactions. Temozolomide can cause similar side effects including hair loss and constipation.

Eligibility Criteria

Inclusion Criteria

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

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I have not been treated with temozolomide, dacarbazine, or PARP inhibitors.

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I have never had myelodysplastic syndrome or acute myeloid leukemia.

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I do not have severe lung disease affecting both lungs.

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I can swallow pills without any issues.

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My cancer can be measured and is at least 1 cm in size, or 1.5 cm if it's in the lymph nodes.

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My tumor is a confirmed advanced pheochromocytoma or paraganglioma that cannot be surgically removed.

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I have no allergies to PARP inhibitors or similar drugs.

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I have not had a bone marrow or cord blood transplant.

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I finished any cancer treatments or surgeries at least 28 days ago and have recovered.

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My kidney function, measured by creatinine levels or clearance, is within the normal range.

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I do not have any current infections.

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My tumor is confirmed to be pheochromocytoma or paraganglioma.

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I am 18 years old or older.

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I had MIBG therapy over 12 weeks ago and received less than 36 mCi/kg in total.

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My cancer has spread and cannot be removed by surgery.

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I am able to get out of my bed or chair and move around.

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I am not currently on combination antiretroviral therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomization to the first documentation of disease progression (per response evaluation criteria in solid tumors [recist] version 1.1) or death, assessed up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomization to the first documentation of disease progression (per response evaluation criteria in solid tumors [recist] version 1.1) or death, assessed up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomization to the first documentation of disease progression (per response evaluation criteria in solid tumors [recist] version 1.1) or death, assessed up to 5 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

Progression-free survival (PFS)

Secondary study objectives

Incidence of adverse events

Objective response

Overall survival (OS)

Other study objectives

Biochemical response

Biomolecular markers associated with clinical outcome

Side effects data

From 2016 Phase 2 trial • 175 Patients • NCT01055314

36%

Febrile neutropenia

31%

Death NOS

30%

Diarrhea

22%

Pain

21%

Hyperglycemia

16%

Anorexia

16%

Infections and infestations - Other, specify

16%

Alanine aminotransferase increased

14%

Hypokalemia

13%

Nausea

11%

Hyponatremia

10%

Weight loss

Aspartate aminotransferase increased

Mucositis oral

Anemia

Vomiting

Constipation

Dehydration

Hypophosphatemia

Platelet count decreased

Sepsis

Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify

Catheter related infection

Colitis

Abdominal pain

Hypotension

White blood cell decreased

GGT increased

Hypocalcemia

Urinary retention

Hypoalbuminemia

Fever

Typhlitis

Anxiety

Neutrophil count decreased

Urinary tract infection

Peripheral motor neuropathy

Enterocolitis

Lipase increased

Pleural effusion

Serum amylase increased

Skin infection

Epistaxis

Urinary tract obstruction

Blood bilirubin increased

Lymphocyte count decreased

Syncope

Wound infection

Dermatitis radiation

Hypertension

Sinus tachycardia

Edema limbs

Bone pain

Dyspnea

Hematuria

Hypercalcemia

Vulval infection

Upper gastrointestinal hemorrhage

Depressed level of consciousness

Thromboembolic event

Stridor

Allergic reaction

Back pain

Lung infection

Urticaria

Acute kidney injury

Muscle weakness lower limb

Musculoskeletal and connective tissue disorder - Other, specify

Pain in extremity

Peripheral sensory neuropathy

Proctitis

Skin ulceration

Apnea

Stoma site infection

Tumor pain

Left ventricular systolic dysfunction

Pancreatitis

Portal hypertension

Rectal hemorrhage

Creatinine increased

Enterocolitis infectious

Hyperkalemia

Investigations - Other, specify

Abdominal distension

Heart failure

Vascular disorders - Other, specify

Anal hemorrhage

Ascites

Vasovagal reaction

Penile pain

Bone marrow hypocellular

Gastrointestinal disorders - Other, specify

Soft tissue infection

Delirium

Tracheitis

Seizure

Hepatobiliary disorders - Other, specify

Esophageal pain

Anal mucositis

Menorrhagia

Sore throat

Anaphylaxis

Fracture

Hydrocephalus

Device related infection

Tooth infection

Gastric ulcer

Sinusitis

Skin and subcutaneous tissue disorders - Other, specify

Pharyngitis

Pyramidal tract syndrome

Anal ulcer

Depression

Ejection fraction decreased

Rash maculo-papular

Pruritus

Myositis

Nail infection

Pain of skin

Pleuritic pain

Pneumonitis

Pneumothorax

Postoperative hemorrhage

Renal and urinary disorders - Other, specify

Respiratory, thoracic and mediastinal disorders - Other, specify

Salivary duct inflammation

Small intestine infection

Alkaline phosphatase increased

Appendicitis

Spinal fracture

Disseminated intravascular coagulation

Ear and labyrinth disorders - Other, specify

Endocrine disorders - Other, specify

Esophageal stenosis

Esophagitis

Gastric hemorrhage

Gum infection

Tumor lysis syndrome

Upper respiratory infection

Hypertriglyceridemia

Hypoxia

Ileus

INR increased

Laryngeal edema

Multi-organ failure

Myelodysplastic syndrome

Oral hemorrhage

Oral pain

Pulmonary edema

Rectal fistula

Rectal pain

Respiratory failure

Bladder spasm

Chest wall pain

Confusion

Congenital, familial and genetic disorders - Other, specify

CPK increased

Dizziness

Encephalopathy

Eye disorders - Other, specify

Generalized muscle weakness

Hoarseness

Hypernatremia

Hypoglycemia

Hypomagnesemia

Insomnia

Irregular menstruation

Irritability

Joint range of motion decreased cervical spine

Kyphosis

Lethargy

Headache

Laryngeal mucositis

Pelvic pain

Esophageal infection

Abdominal infection

Acidosis

Anal fistula

Fall

Fatigue

Gait disturbance

100%

80%

60%

40%

20%

Study treatment Arm

Group 1 (Chemotherapy, Radiation Therapy, Cixutumumab)

Group 2 (Chemotherapy, Radiation Therapy, Temozolomide)

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

Active Control

Group I: Arm I (temozolomide, olaparib)Experimental Treatment6 Interventions

Patients receive temozolomide PO QD and olaparib PO BID on days 1-7. Treatment with temozolomide repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Cycles of olaparib repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT with contrast or MRI throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression.

Group II: Arm II (temozolomide)Active Control5 Interventions

Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with contrast or MRI throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Biospecimen Collection

2004

Completed Phase 3

~2020

Olaparib

2007

Completed Phase 4

~2190

Temozolomide

2010

Completed Phase 3

~1880

0 / 17Eligibility 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

Olaparib, a PARP inhibitor, works by preventing cancer cells from repairing their DNA, leading to cell death. Temozolomide, a chemotherapy drug, damages the DNA of cancer cells, stopping them from dividing and growing. For Pheochromocytoma patients, this combination is significant because it targets the cancer cells' ability to repair and proliferate, potentially reducing tumor growth and improving treatment efficacy.