What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer include chemotherapy regimens such as FOLFIRINOX, which combines fluorouracil, leucovorin, irinotecan, and oxaliplatin. These treatments can cause side effects like neutropenia, fatigue, diarrhea, neuropathy, and nausea. Treatments targeting the Akt/mTOR pathway, similar to ABTL0812, may also lead to side effects such as hyperglycemia, mucositis, and increased risk of infections due to immunosuppression. It is important for patients to discuss these potential side effects with their healthcare provider to manage them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for pancreatic cancer, including combination chemotherapy regimens like FOLFIRINOX (leucovorin, fluorouracil, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel. These treatments have shown efficacy in improving survival rates in patients with metastatic pancreatic cancer. While ABTL0812, which induces autophagy and inhibits the Akt/mTOR pathway, is still under investigation, other targeted therapies that affect similar pathways include everolimus, an mTOR inhibitor, which is approved for certain types of neuroendocrine tumors of pancreatic origin.

What other types of research exist?

Promising novel alternatives to ABTL0812 for pancreatic cancer patients include: 1) PARP inhibitors (e.g., olaparib) for patients with BRCA mutations, 2) Immunotherapy agents such as pembrolizumab for patients with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR), 3) Targeted therapies like larotrectinib or entrectinib for tumors with NTRK gene fusions, and 4) Newer agents targeting the KRAS mutation, such as sotorasib. These alternatives have shown potential in recent clinical trials and may be considered for treatment in 2024.

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Cancer Metabolism Inhibitor

ABTL0812 + FOLFIRINOX for Pancreatic Cancer (PanC-ASAP Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Ability Pharmaceuticals SL

Eligibility Criteria Checklist

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

Must have

Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 guidelines with at least one 'target lesion' to be used to assess response. Tumors within a previously irradiated field will be designated as 'non-target' lesions unless progression is documented

Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

Must not have

Patient had myocardial infarction within ≤ 6 months prior to study entry, LVEF < 50%, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina pectoris, or unstable cardiac arrhythmia requiring medication

Patients previously treated with an inhibitor of the PI3K/Akt/mTOR pathway by a systemic route

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Summary

This trial tests a new drug, ABTL0812, combined with usual chemotherapy for patients with advanced pancreatic cancer. The goal is to see if ABTL0812 can make the chemotherapy more effective. The study includes two stages: an initial stage to find the best amount and a second stage to compare the new combination against usual care.

Who is the study for?

Adults with confirmed metastatic pancreatic cancer, good blood counts and organ function, who haven't been treated with PI3K/Akt/mTOR pathway inhibitors. They must not have other serious medical conditions or a history of certain heart diseases. Participants need to use effective contraception and be able to follow the study protocol.

What is being tested?

The trial is testing ABTL0812 in combination with FOLFIRINOX chemotherapy as a first-line treatment for metastatic pancreatic cancer. It's an open-label Phase I followed by a randomized Phase II study comparing this combination against placebo plus FOLFIRINOX.

What are the potential side effects?

Potential side effects may include typical chemotherapy-related issues like nausea, fatigue, lowered blood cell counts leading to increased infection risk, liver enzyme changes, diarrhea or allergic reactions. Specific side effects of ABTL0812 are not detailed but could align with common drug class effects.

Eligibility Criteria

Inclusion Criteria

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

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I have at least one tumor that can be measured and tracked for treatment response.

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I am fully active or can carry out light work.

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I am older than 18 years.

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My blood counts meet the required levels without needing transfusions.

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My cancer has spread to other parts of my body.

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I am using two effective forms of birth control during and 6 months after the study.

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My cancer is a confirmed type of pancreatic cancer.

Exclusion Criteria

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

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I have had a heart attack in the last 6 months or have serious heart issues.

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I have been treated with a PI3K/Akt/mTOR pathway inhibitor.

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I am able to make my own health decisions and am not under legal supervision.

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My cancer is not classified as carcinoma, adenocarcinoma, or ductal adenocarcinoma.

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I have a history of chronic diarrhea or inflammation in my colon or rectum, or unresolved blockages.

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I have active Hepatitis B/C, HIV, or Covid-19 that is not under control.

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My cancer is advanced but hasn't spread far and can be surgically removed.

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I had chemotherapy for early-stage cancer that was near vital organs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

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

Phase I - RP2D

Phase II - PFS

Secondary study objectives

Adverse events

DOR

ORR

+5 more

Other study objectives

PK - AUC

PK - Cmax

Quality of Life Questionnaire QLC-C30

+1 more

Side effects data

From 2022 Phase 3 trial • 528 Patients • NCT03504423

75%

Nausea

67%

Diarrhoea

59%

Fatigue

46%

Anaemia

43%

Decreased appetite

41%

Neuropathy peripheral

41%

Vomiting

37%

Constipation

37%

Hypokalaemia

35%

Abdominal pain

34%

Weight decreased

31%

Platelet count decreased

28%

Neutrophil count decreased

27%

Blood alkaline phosphatase increased

23%

Alanine aminotransferase increased

22%

Aspartate aminotransferase increased

21%

Alopecia

21%

Peripheral sensory neuropathy

21%

Hypoalbuminaemia

20%

Hyponatraemia

20%

Stomatitis

20%

Dysgeusia

19%

Neutropenia

19%

Dizziness

18%

Hypomagnesaemia

17%

Back pain

17%

Oedema peripheral

17%

Hypertension

16%

Hypophosphataemia

15%

Pyrexia

15%

Dehydration

15%

White blood cell count decreased

14%

Lymphocyte count decreased

14%

Insomnia

13%

Asthenia

13%

Paraesthesia

13%

Thrombocytopenia

13%

Hyperglycaemia

12%

Hypocalcaemia

12%

Dyspepsia

12%

Cough

12%

Temperature intolerance

11%

Dyspnoea

10%

Mucosal inflammation

10%

Abdominal distension

10%

Anxiety

International normalised ratio increased

Activated partial thromboplastin time prolonged

Headache

Gastrooesophageal reflux disease

Hiccups

Hypotension

Epistaxis

Abdominal pain upper

Flatulence

Rash

Pulmonary embolism

Dry mouth

Rhinorrhoea

Arthralgia

Depression

Dry skin

Blood bilirubin increased

Pruritus

Myalgia

Non-cardiac chest pain

Ascites

Palmar-plantar erythrodysaesthesia

Muscular weakness

Chills

Deep vein thrombosis

Infusion related reaction

Sinus tachycardia

Cholinergic syndrome

Embolism

Fall

Sepsis

Haematochezia

Dysphagia

Haemorrhoids

Weight increased

Hyperkalaemia

Hypoglycaemia

Muscle spasms

Pain in extremity

Oropharyngeal pain

Hyperhidrosis

Syncope

Hypertensive crisis

Vision blurred

blood creatinine increased

Musculoskeletal pain

Candida infection

Oral pain

Upper respiratory tract infection

Dysphonia

Leukocytosis

Rhinitis allergic

Pneumonia

Rhinitis

Hyperbilirubinaemia

Tachycardia

Diabetes mellitus

General physical health deterioration

Febrile neutropenia

Hypernatraemia

Flushing

Urinary tract infection

Flank pain

Contusion

Colitis

Night sweats

Abdominal discomfort

Atrial fibrillation

Abdominal pain lower

Oesophagitis

Proctalgia

Gastritis

Hypermagnesaemia

Dysuria

Pancreatic enzymes decreased

Influenza

Dysarthria

Hyperphosphataemia

Device related infection

Bile duct obstruction

Immune system disorders

Bacteraemia

Neutrophil count increased

Acute kidney injury

Pollakiuria

Pleural effusion

Localised oedema

Corona virus infection

Gamma-glutamyltransferase increased

Tremor

Pain

Urinary retention

Skin hyperpigmentation

Gastrointestinal haemorrhage

Catheter site pain

Peripheral swelling

Cholecystitis

Catheter site infection

Oral candidiasis

Lymphocyte count increased

Neck pain

Disturbance in attention

Dysaesthesia

Hypoaesthesia

Micturition urgency

Nasal congestion

Upper gastrointestinal haemorrhage

Eructation

Urinary incontinence

Bradycardia

Polyneuropathy

Septic shock

Rash maculo-papular

Thrombophlebitis

Rectal haemorrhage

Electrocardiogram QT prolonged

Bone pain

Musculoskeletal chest pain

Proteinuria

Malnutrition

Oral herpes

Erythema

White blood cell count increased

Rash papular

Sinus bradycardia

Paraesthesia oral

Cholestasis

Memory impairment

Throat irritation

Oral fungal infection

Palpitations

Visual impairment

blood phosphorus decreased

Joint swelling

Dyspnoea exertional

Odynophagia

Ecchymosis

Orthostatic hypotension

Biliary dilatation

Hypersensitivity

Productive cough

Abdominal hernia

Diabetic ketoacidosis

Atelectasis

Pneumonitis

Scab

Enterocolitis

Large intestine perforation

Cholangitis

Cholangitis acute

Vulvovaginal mycotic infection

Pelvic pain

Venous thrombosis

Ventricular extrasystoles

Dyshidrotic eczema

Intestinal obstruction

Biliary tract infection

Blood bilirubin decreased

Nasal dryness

Enteritis

Gastrointestinal pain

Gastroenteritis

Herpes zoster

Ligament sprain

Lymphadenopathy

Gallbladder obstruction

Obstruction gastric

Drug hypersensitivity

Cellulitis

Herpes simplex

Haematuria

Mouth ulceration

Glucose tolerance impaired

Ataxia

Hypertriglyceridaemia

Pancreatic failure

Clostridium difficile colitis

Renal failure

Urinary tract pain

Cerebrovascular accident

Lip ulceration

Melaena

Pancreatitis

Salivary hypersecretion

Small intestinal obstruction

Early satiety

Feeling cold

Generalised oedema

Rash pustular

Gingival pain

Pharyngeal inflammation

Dermatitis acneiform

Skin discolouration

Jaundice cholestatic

Heart rate increased

Protein total decreased

Rash erythematous

Clostridium difficile infection

Pancytopenia

Blood creatinine increased

Leukopenia

Abnormal faeces

Aphthous ulcer

Pharyngitis

Limb injury

Post procedural complication

Thermal burn

Transaminases increased

Gout

Encephalopathy

Presyncope

Agitation

Mental status changes

Chromaturia

Sneezing

Upper-airway cough syndrome

Sinusitis

Dizziness postural

Gait disturbance

Procedural pain

Hepatic enzyme increased

Aphasia

Pallor

Device malfunction

Laryngeal inflammation

Decubitus ulcer

Device occlusion

Urticaria

Faeces pale

Ischaemic hepatitis

Type 2 diabetes mellitus

Tumour pain

Thrombosis

Confusional state

Nail discolouration

Haematemesis

Chest discomfort

Abscess

Fistula

Peroneal nerve palsy

Toothache

Device related thrombosis

Prothrombin time prolonged

Nocturia

Hepatocellular injury

Cardiac murmur

Speech disorder

Duodenal obstruction

Lower gastrointestinal haemorrhage

Oedema

Swelling

Neurotoxicity

Tooth fracture

Hypercalcaemia

Stress cardiomyopathy

Muscle twitching

Erythema multiforme

Acute left ventricular failure

Blood sodium decreased

Malaise

Glossodynia

Haemorrhoidal haemorrhage

Steatorrhoea

Hypoxia

Restlessness

Blood albumin decreased

Dry eye

Eye pain

Lacrimation increased

Ocular hyperaemia

Photophobia

blood cholesterol increased

blood magnesium decreased

100%

80%

60%

40%

20%

Study treatment Arm

CPI-613, mFolfirinox

Folfirinox

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B) PLACEBO + FOLFIRINOXExperimental Treatment2 Interventions

FOLFIRINOX will be dosed according to the standard following regimen: * oxaliplatin 85 mg/m2, administered as 2-hour iv infusion * leucovorin 400 mg/m2, administered as 2-hour iv infusion * irinotecan 180 mg/m2, administered as 1.5-hour iv infusion * fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities. Placebo will be administered at the same volume than ABTL0812 in arm A) FOLFIRINOX, then daily during chemotherapy cycles. Also, placebo will be maintained once chemotherapy is discontinued.

Group II: Arm A) ABTL0812 + FOLFIRINOXExperimental Treatment2 Interventions

FOLFIRINOX will be dosed according to the standard following regimen: * oxaliplatin 85 mg/m2, administered as 2-hour iv infusion * leucovorin 400 mg/m2, administered as 2-hour iv infusion * irinotecan 180 mg/m2, administered as 1.5-hour iv infusion * fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities. ABTL0812 will be administered daily at its RP2D. ABTL0812 will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, ABTL0812 will be maintained once chemotherapy is discontinued, if ABTL0812 is tolerated and if the patient is in response or stable disease.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

ABTL0812

2014

Completed Phase 2

~180

Folfirinox

2018

Completed Phase 3

~760

0 / 15Eligibility 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 treatments for pancreatic cancer often target key cellular pathways to inhibit tumor growth and promote cancer cell death. ABTL0812, for example, induces autophagy and inhibits the Akt/mTOR pathway, which is crucial because these pathways are involved in cell survival and proliferation. By inducing autophagy, cancer cells are driven to a state of self-digestion, leading to cell death. Inhibiting the Akt/mTOR pathway disrupts signals that promote tumor growth and survival. Other treatments, such as gemcitabine, work by interfering with DNA replication, while newer targeted therapies may inhibit specific genetic mutations or proteins involved in cancer progression. Understanding these mechanisms helps in tailoring treatments to effectively combat pancreatic cancer, potentially improving patient outcomes.

Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome.