What is the mechanism of action of this treatment?

Common cancer treatments often involve enzyme inhibition, which is crucial for targeting specific pathways that cancer cells use to grow and survive. Cabozantinib, a tyrosine kinase inhibitor, blocks enzymes involved in tumor growth and angiogenesis, thereby starving the tumor of nutrients and inhibiting its growth. Pamiparib, a PARP inhibitor, prevents cancer cells from repairing DNA damage, leading to cell death. These targeted therapies are significant for cancer patients as they offer the potential for more effective treatments with fewer side effects compared to traditional chemotherapy, improving overall outcomes and quality of life.

What side effects are associated with this type of intervention?

Enzyme inhibition treatments for cancer, such as Cabozantinib and Pamiparib, commonly cause a range of side effects. These can include fatigue, nausea, diarrhea, decreased appetite, and hyperglycemia. More severe adverse events may involve increased levels of amylase and lipase, anemia, and decreased neutrophil counts. While these treatments can be effective in halting tumor growth, patients often experience significant treatment-related toxicity that requires careful management.

What prior FDA approvals exist?

Several enzyme inhibitors have received FDA approval for cancer treatment. Tyrosine kinase inhibitors like cabozantinib, which targets multiple kinases including MET, VEGFR, and RET, are approved for various cancers such as medullary thyroid cancer and renal cell carcinoma. Other similar drugs include vandetanib and lenvatinib. PARP inhibitors like pamiparib, which inhibit the enzyme poly (ADP-ribose) polymerase, are used in cancers with BRCA mutations. FDA-approved PARP inhibitors include olaparib, rucaparib, and niraparib, which are used for ovarian, breast, and prostate cancers. These drugs work by blocking enzymes essential for DNA repair, thereby preventing cancer cell growth.

What other types of research exist?

Promising alternatives to Cabozantinib and Pamiparib for cancer treatment in 2024 include Niraparib, Olaparib, Selpercatinib, Infigratinib, Pembrolizumab, and Nivolumab. These therapies have shown efficacy in clinical trials for various advanced or refractory cancers.

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Tyrosine Kinase Inhibitor

Cabozantinib + Pamiparib for Advanced Cancer

Phase 1

Waitlist Available

Led By Siqing Fu

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Patients must have one of the specified genetic and pathologic features as defined in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory

Patients must be able to take oral medications without medical history of malabsorption or other chronic gastrointestinal disease

Must not have

Recent vaccination with live vaccine

Concomitant anticoagulation with specified agents

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing cabozantinib and pamiparib in patients with advanced or treatment-resistant solid tumors. The goal is to find the best dose and understand the side effects. These drugs work by blocking enzymes that cancer cells need to grow.

Who is the study for?

Adults with advanced solid tumors that are resistant to standard treatments or have no standard treatment options available. Participants must have specific genetic markers related to tumor growth, be able to take oral medication, and not have had certain recent treatments. They should also meet various health criteria like adequate blood cell counts and organ function, agree to use effective contraception, and not be pregnant or breastfeeding.

What is being tested?

The trial is testing the combination of two drugs, Cabozantinib and Pamiparib, for their effectiveness in stopping tumor growth by inhibiting enzymes needed for cell proliferation. It aims to determine the optimal dosages and document any side effects when used together on patients with refractory advanced solid tumors.

What are the potential side effects?

Potential side effects may include but are not limited to fatigue, digestive issues such as nausea or diarrhea, changes in blood pressure or heart rhythm disturbances (QTc prolongation), liver enzyme alterations indicating potential liver damage, possible bleeding complications if taking anticoagulants concurrently, and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

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

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My condition has a specific genetic feature confirmed by a certified lab.

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I can take pills and do not have chronic stomach or absorption problems.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am willing to provide tissue samples for the study.

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I have not been treated with drugs that target PARP and VEGF at the same time.

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My cancer can be measured or seen on scans.

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I am 18 years old or older.

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I haven't had radiation aimed at relieving symptoms on my only cancer spots during the study.

Exclusion Criteria

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

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I have not received a live vaccine recently.

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I am currently taking blood thinners.

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I have brain metastases or cranial epidural disease.

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I do not have any serious wounds, thyroid issues, or severe liver problems.

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I am on treatment for HIV or have active hepatitis B or C.

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My cancer has spread to major blood vessels or specific areas in my lungs.

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I am currently receiving treatment for cancer.

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I have not had significant bleeding or blood in my urine, vomit, or cough.

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I have recently undergone radiation therapy or treatment with radioactive substances.

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I have heart problems or recent blood clot issues.

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I have moderate to severe numbness, tingling, or pain in my hands or feet.

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I have a serious gut condition that could lead to complications.

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I do not have a serious infection or condition that could interfere with treatment.

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I still have side effects from previous treatments.

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I cannot swallow pills.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 months

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

Incidence of adverse events

Side effects data

From 2022 Phase 2 trial • 45 Patients • NCT02101736

95%

HYPOTHYROIDISM

73%

DIARRHEA

55%

WEIGHT LOSS

50%

FATIGUE

41%

ALANINE AMINOTRANSFERASE INCREASED

41%

Neutrophil Count Decreased

41%

ASPARTATE AMINOTRANSFERASE INCREASED

41%

VOMITING

41%

ANOREXIA

41%

NAUSEA

36%

PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME

36%

HEADACHE

36%

PAIN IN EXTREMITY

36%

HYPERTENSION

32%

PROTEINURIA

32%

PAIN

27%

White Blood Cell Count Decreased

27%

ABDOMINAL PAIN

23%

Decreased Platelet Count

23%

PLATELET COUNT DECREASE

23%

HYPONATREMIA

23%

Platelet Count Decreased

23%

Skin Hypopigmentation

23%

Renal & Urinary Disorders - Other, Ketonuria

23%

HAIR COLOR CHANGE

18%

HEMOGLOBIN INCREASED

18%

HYPOKALEMIA

18%

Upper Respiratory Infection

18%

HYPOPHOSPHATEMIA

18%

Alopecia

18%

Hyperkalemia

14%

Rash Acneiform

14%

Pruritis

14%

Rash Maculopapular

14%

HYPOGLYCEMIA

14%

HYPERGLYCEMIA

14%

BILIRUBIN INCREASED

14%

ACNEIFORM RASH

14%

Cough

14%

Blood Bilirubin Increased

14%

DIZZINESS

14%

Skin And Subcutaneous Disorders - Other, Achromotricia

14%

CONSTIPATION

14%

Fever

Papulopustular Rash

ALKALINE PHOSPHATASE INCREASED

LIPASE INCREASED

Creatinine Increased

Back Pain

ABSOLUTE NEUTROPHIL COUNT DECREASED

Paresthesia

TUMOR PAIN

Skin And Subcutaneous Tissue Disorders- Other, Rash Unspecified

ORAL PAIN

LYMPHOCYTE COUNT DECREASED

NASAL CONGESTION

WEIGHT GAIN

HYPOCALCEMIA

DRY SKIN

Gastrointestinal Disorders - Other, Buccal Cyst

Allergic Rhinitis

Hypotension

Skin And Subcutaneous Tissue Disorders- Other, Sore On Lips

Hypertension

SERUM AMYLASE INCREASED

Behaviour Disturbance

Investigations - Other, Eosinophilia

Sore Throat

JOINT RANGE OF MOTION DECREASED

Joint Range Of Motion Decreased

HEMATURIA

ANXIETY

Hypermagnesemia

Rash Ezcematoid

Musculoskeletal And Connective Tissue Disorder - Other, Tendinitis

Scalp Pain

DIFFICULTY WALKING, BACK PAIN, BOWEL/BLADDER URGENCY, LEGS GAVE OUT, AND PARESTHESIAS

Psychiatric Disorders - Other, Mood Swings

URINARY URGENCY

Sinus Tachycardia

Periodontal Disease

Peripheral Sensory Neuropathy

Scalp Lesion

Myalgia

Tooth Infection

RASH

Gastrointestinal Disorders - Other, Dental Pain

Peripheral Motor Neuropathy

Tachycardia

URINARY FREQUENCY

Conjunctivitis

Neuropathy

Sinusitis

Syncope

Activated Partial Thromboplastin Time Prolonged

Breast Pain

INSOMNIA

Infections And Infestations - Other, Gi Viral Infection

Stomach Pain

TENDONITIS

SKIN INFECTION

HYPOMAGNESEMIA

Muscle Weakness Lower Limb

Muscle Weakness Upper Limb

Skin And Subcutaneous Disorders - Other, Dry Skin Patches

Skin And Subcutaneous Tissue Disorders - Other, Skin Color Change

Skin And Subcutaneous Tissue Disorders- Other, Blister/Bug Bite On Finger

Surgical & Medical Procedures - Other, Dental Extractions

Investigations - Other, International Normalized Ration Increased

Skin And Subcutaneous Tissue Disorders- Other, Erythema

Infections And Infestations - Other, Covid-19

Investigations - Other, Increased Mean Corpuscular Volume

Skin And Subcutaneous Tissue Disorders- Other, Transient Erythema

SUBJECT WAS ADMITTED TO THE HOSPITAL ON 10/24/20 WITH GRADE 2 WEIGHT LOSS THAT THE PHYSICIAN FELT NE

Injury, Poisoning And Procedural Complications - Other, Ankle Injury

Injury, Poisoning And Procedural Complications- Other, Scalp Laceration

Musculoskeletal And Connective Tissue Disorders - Other, Extremity Cramps

Skin And Subcutaneous Tissue Disorders- Other, New Freckles/Moles

SINUS BRADYCARDIA

HYPERTHYROIDISM

Creatine Phosphokinase Increased

Skin And Subcutaneous Tissue Disorders - Other: Blue Lips (Not Cyanosis)

Urine Discoloration

SPINAL CORD COMPRESSION

ANEMIA

PARONYCHIA

BRUISING

HYPOALBUMINEMIA

Ear And Labyrinth Disorders - Other, Impacted Cerumen

Ear Pain

Elevated Amylase

Facial Pain

Gastrointestinal Disorders - Other, Stomatitis

Hoarseness

Laryngitis

Leg Pain

Localized Edema

Lung Infection

Metabolism And Nutrition Disorders - Other, Decreased Oral Intake

Metabolism Other - Decreased Vitamin D

Metbolism And Nutrition Disorders - Other, Hyperchloremia

Mucositis Oral

100%

80%

60%

40%

20%

Study treatment Arm

Cohort B

Cohort A

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: Treatment (cabozantinib, pamiparib)Experimental Treatment2 Interventions

Patients receive cabozantinib PO QD and pamiparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cabozantinib

2020

Completed Phase 2

~1760

Pamiparib

2017

Completed Phase 2

~750

0 / 23Eligibility 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

Common cancer treatments often involve enzyme inhibition, which is crucial for targeting specific pathways that cancer cells use to grow and survive. Cabozantinib, a tyrosine kinase inhibitor, blocks enzymes involved in tumor growth and angiogenesis, thereby starving the tumor of nutrients and inhibiting its growth. Pamiparib, a PARP inhibitor, prevents cancer cells from repairing DNA damage, leading to cell death. These targeted therapies are significant for cancer patients as they offer the potential for more effective treatments with fewer side effects compared to traditional chemotherapy, improving overall outcomes and quality of life.

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