What is the mechanism of action of this treatment?

The most common treatments for Biliary Tract Cancer (BTC) include targeted therapies like PARP inhibitors and immune checkpoint inhibitors. Rucaparib, a PARP inhibitor, works by blocking the PARP enzyme involved in DNA repair, leading to the accumulation of DNA damage and cancer cell death, especially in cancers with BRCA mutations. Nivolumab, a PD-1 inhibitor, enhances the immune system's response against cancer cells by blocking the PD-1 pathway, which cancer cells use to evade immune detection. These treatments are significant for BTC patients as they offer targeted and potentially more effective approaches to combat the cancer.

What side effects are associated with this type of intervention?

Rucaparib, a PARP inhibitor, commonly causes side effects such as nausea, fatigue, vomiting, and anemia. Nivolumab, a PD-1 inhibitor, can lead to immune-related adverse effects including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Other common treatments for BTC, such as chemotherapy (e.g., gemcitabine and cisplatin), often result in side effects like myelosuppression, nausea, vomiting, and increased risk of infection. Targeted therapies may also cause specific toxicities depending on the molecular target, such as hepatotoxicity or gastrointestinal disturbances.

What prior FDA approvals exist?

As of now, there are no specific FDA approvals for the combination of Rucaparib (a PARP inhibitor) and Nivolumab (a PD-1 inhibitor) for the treatment of Biliary Tract Cancer (BTC). However, other treatments involving PD-1 inhibitors, such as Nivolumab, have shown promise in various cancers, including BTC. For instance, Nivolumab has been studied in combination with other agents for its efficacy in BTC. Similarly, PARP inhibitors like Rucaparib are being explored for their potential benefits in cancers with homologous recombination repair deficiencies. While these specific combinations are still under investigation, the use of immunotherapy and targeted therapies represents a growing area of interest in the treatment of BTC.

What other types of research exist?

Promising novel alternatives for BTC patients include: 1) Ceritinib in combination with gemcitabine and cisplatin, especially for tumors with ALK or ROS1 fusions, due to its manageable toxicity profile and clinical benefits observed in cholangiocarcinoma patients. 2) Olaparib monotherapy for BRCA1/2-mutated intrahepatic cholangiocarcinoma, which has shown efficacy in a case report. 3) Dabrafenib plus trametinib for BRAFV600E-mutated biliary tract cancer, which has demonstrated positive results in phase 2 trials.

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Checkpoint Inhibitor

Rucaparib + Nivolumab for Biliary Tract Cancer

Phase 2

Waitlist Available

Led By Vaibhav Sahai, MBBS, MS

Research Sponsored by University of Michigan Rogel Cancer Center

Eligibility Criteria Checklist

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

Must have

Available archived tissue

ECOG performance status of 0-1

Must not have

Participants with an active, known or suspected autoimmune disease which may affect vital organ function, or has/may require systemic immunosuppressive therapy for management.

Active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to two years post treatment discontinuation

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if using rucaparib and nivolumab together can help patients with Biliary Tract Cancer live longer. Rucaparib stops cancer cells from repairing themselves, and nivolumab boosts the immune system to fight the cancer.

Who is the study for?

This trial is for adults with advanced biliary tract cancer who've had platinum-based chemotherapy but can't have surgery or other curative treatments. They must be in good physical condition, not have certain other cancers or serious medical issues, and agree to use effective contraception.

What is being tested?

The study tests if rucaparib combined with nivolumab improves survival for patients after first-line platinum chemotherapy. It's for those whose disease hasn't worsened during initial treatment and who meet specific health criteria.

What are the potential side effects?

Rucaparib may cause nausea, fatigue, blood count changes, and liver enzyme alterations. Nivolumab can lead to immune-related side effects like inflammation of organs, skin rash, hormone gland problems, and infusion reactions.

Eligibility Criteria

Inclusion Criteria

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

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I have tissue samples from previous procedures stored.

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I am fully active or can carry out light work.

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I've had platinum-based chemo for 4-6 months for advanced bile duct cancer without it getting worse.

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I am 18 years old or older.

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My liver function is moderately to mildly impaired.

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I can safely undergo CT or MRI scans with contrast.

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My cancer is a type of biliary tract cancer that cannot be removed or cured with surgery.

Exclusion Criteria

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

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I have an autoimmune disease that affects my organs or requires immunosuppressive therapy.

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I have another active cancer besides non-melanoma skin cancer or cervical carcinoma in situ.

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I do not have any current, uncontrolled infections.

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I have had a solid organ transplant or brain metastasis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to two years post treatment start

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to two years post treatment start

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to two years post treatment start for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Proportion of Patients Alive and Without Radiological or Clinical Progression at 4 Months

Secondary study objectives

Progression Free Survival (PFS) Time as Measured From Start of 1st Line Platinum Therapy

Progression Free Survival (PFS) Time as Measured From Treatment Start

The Proportion of Patients That Respond to Treatment

Side effects data

From 2022 Phase 3 trial • 564 Patients • NCT01968213

76%

Nausea

70%

Combined Asthenia/Fatigue

52%

Fatigue

39%

Combined Anaemia and/or decreased hemoglobin

38%

Constipation

38%

Vomiting

37%

Anaemia

35%

Diarrhoea

35%

Alanine aminotransferase increased

34%

Combined ALT/AST increased

33%

Abdominal pain

31%

Dysgeusia

29%

Combined Thrombocytopenia and/or decreased platelets

27%

Aspartate aminotransferase increased

25%

Decreased appetite

23%

Asthenia

22%

Arthralgia

20%

Headache

19%

Combined Neutropenia and/or decreased ANC

19%

Photosensitivity reaction

18%

Cough

17%

Thrombocytopenia

17%

Blood creatinine increased

16%

Dyspepsia

16%

Insomnia

16%

Dizziness

15%

Pruritus

15%

Rash

15%

Dyspnoea

15%

Abdominal pain upper

15%

Back pain

15%

Pyrexia

14%

Platelet count decreased

14%

Neutropenia

13%

Abdominal distension

13%

Upper respiratory tract infection

12%

Hypertension

12%

Oedema peripheral

12%

Hypomagnesaemia

10%

Nasopharyngitis

10%

Alopecia

10%

Taste disorder

10%

Dry skin

10%

Urinary tract infection

Mucosal inflammation

Influenza

Depression

Stomatitis

Erythema

Hypercholesterolaemia

Anxiety

Neutrophil count decreased

Dry mouth

Weight decreased

Myalgia

Oropharyngeal pain

White blood cell count decreased

Gastrooesophageal reflux disease

Influenza like illness

Hot flush

Neck pain

Pain in extremity

Blood alkaline phosphatase increased

Muscle spasms

Sinusitis

Combined Anemia and/or low hemoglobin

General physical health deterioration

Incarcerated hernia

Intestinal obstruction

Sepsis

Muscular weakness

Combined Thrombocytopenia and/or low platelets

Osteoarthritis

Gastrointestinal pain

Pulmonary embolism

Febrile neutropenia

Pancytopenia

Small intestinal obstruction

Dehydration

Combined Netropenia and/or low ANC

Malignant melanoma

Malignant neoplasm progression

Myelodysplastic syndrome

Seizure

Acute kidney injury

Renal failure

100%

80%

60%

40%

20%

Study treatment Arm

Rucaparib 600 mg Tablets

Placebo Tablets

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: Rucaparib and NivolumabExperimental Treatment2 Interventions

Rucaparib 600 mg PO BID days 1-28 Nivolumab 240 mg IV days 1 and 15

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2014

Completed Phase 3

~5220

Rucaparib

2016

Completed Phase 3

~2020

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 Biliary Tract Cancer (BTC) include targeted therapies like PARP inhibitors and immune checkpoint inhibitors. Rucaparib, a PARP inhibitor, works by blocking the PARP enzyme involved in DNA repair, leading to the accumulation of DNA damage and cancer cell death, especially in cancers with BRCA mutations. Nivolumab, a PD-1 inhibitor, enhances the immune system's response against cancer cells by blocking the PD-1 pathway, which cancer cells use to evade immune detection. These treatments are significant for BTC patients as they offer targeted and potentially more effective approaches to combat the cancer.

Future directions in drug development in pancreatic cancer.EGFR Target Therapy Combined with Gemox for Advanced Biliary Tract Cancers: a Meta-analysis based on RCTs.Dramatic response to dabrafenib and trametinib combination in a BRAF V600E-mutated cholangiocarcinoma: implementation of a molecular tumour board and next-generation sequencing for personalized medicine.