Trial Title:
EF-39 PANOVA-4: Study of Tumor Treating Fields Concomitant With Atezolizumab, Gemcitabine and Nab-Paclitaxel as First-LineTreatment for Metastatic Pancreatic Ductal Adenocarcinoma
NCT ID:
NCT06390059
Condition:
Metastatic Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Paclitaxel
Gemcitabine
Atezolizumab
Conditions: Keywords:
EF-39
PANOVA-4
metastatic pancreatic cancer
tumor treating fields
atezolizumab
gemcitabine and nab-paclitaxel
first line treatment
mPDAC
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Prospective, open-label, single arm, multi-center, historical control pilot study.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Device
Intervention name:
Tumor Treating Fields
Description:
The NovoTTF-200T is a portable, battery operated system intended for continuous home use,
which delivers TTFields at a frequency of 150kHz to the patient by means of insulated
transducer arrays. The NovoTTF-200T produces TTFields that exert electric forces intended
to disrupt cancer cell division.
TTFields at 150 kHz application will be continuous for at least 18 hours a day on
average. TTFields will be continued until disease progression according to RECISTv1.1 or
loss of clinical benefit.
Arm group label:
TTFields + atezolizumab + gemcitabine and nab-paclitaxel
Other name:
NovoTTF-200T
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Atezolizumab is a humanized IgG1 monoclonal antibody which targets human PD-L1and
inhibits its interaction with its receptors, PD-1 and B7.1 (CD80). Both of these
interactions are reported to provide inhibitory signals to T cells. Atezolizumab is
administered as an intravenous solution.
Atezolizumab may continue until disease progression according to RECIST v1.1 or loss of
clinical benefit.
Arm group label:
TTFields + atezolizumab + gemcitabine and nab-paclitaxel
Other name:
Tecentriq (Brand name)
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Gemcitabine is a standard of care chemotherapy drug administered as an intravenous
infusion.
Gemcitabine may continue until disease progression according to RECIST v1.1 or loss of
clinical benefit.
Arm group label:
TTFields + atezolizumab + gemcitabine and nab-paclitaxel
Other name:
Gemzar
Intervention type:
Drug
Intervention name:
nab-paclitaxel
Description:
Nab-paclitaxel is a standard of care chemotherapy drug administered as an intravenous
infusion.
Nab-paclitaxel may continue until disease progression according to RECIST v1.1 or loss of
clinical benefit.
Arm group label:
TTFields + atezolizumab + gemcitabine and nab-paclitaxel
Other name:
Abraxane
Summary:
The PANOVA-4 study is designed to evaluate the safety and efficacy of Tumor Treating
Fields (TTFields) therapy together with atezolizumab, gemcitabine and nab-paclitaxel, for
the treatment of metastatic pancreatic cancer. The study is intended for patients who
have been diagnosed with metastatic pancreatic cancer and have not received prior
systemic therapy.
Detailed description:
The PANOVA-4 study is an international, multi-center, research study for female and male
adult patients diagnosed with metastatic pancreatic ductal adenocarcinoma (mPDAC).
The purpose of the study is to test the efficacy and safety of TTFields, delivered using
the NovoTTF-200T Treatment Kit, concomitantly with atezolizumab, gemcitabine and
nab-paclitaxel as first line treatment for Metastatic Pancreatic Ductal Adenocarcinoma
(mPDAC).
The chemotherapy used in this study, gemcitabine and nab-paclitaxel, are standard-of-care
treatment for metastatic pancreatic cancer. The atezolizumab drug and the NovoTTF-200T
device are investigational for this tumor type. Atezolizumab is an immunotherapy drug
that works with the immune system to help fight cancer. NovoTTF-200T is a non-invasive
medical device that delivers Tumor Treating Fields (TTFields) at 150kHz to the cancer in
the abdominal region, where the tumor is located.
The study is expected to enroll 76 patients in centers around the world. The expected
duration on study per patient is approximately 12 months.
Patients with previously untreated mPDAC who meet all inclusion criteria and none of the
exclusion criteria as determined by the investigator will initiate study treatment within
28 days from signing the Informed Consent Form (ICF) to receive TTFields (150 kHz),
atezolizumab, gemcitabine and nab-paclitaxel.
All patients enrolled in the study will receive continuous TTFields therapy concomitant
with monthly atezolizumab treatments for their metastatic pancreatic cancer and weekly
gemcitabine and nab-paclitaxel.
While on the study, patients will be asked to visit the clinic every 4 weeks, in order to
perform a physical examination, blood tests,and some other assessments. Patients will be
asked to have a radiological examination (CT scan of the chest abdomen and pelvis) every
8 weeks to assess the status of the disease.
Study treatments will continue until disease progression according to RECIST v1.1, or
loss of clinical benefit.
Patients who experience disease progression will be permitted to continue study
treatments if there is evidence of clinical benefit.
Subjects will return to the clinic for one final visit approximately 30 days after
discontinuation of the last study treatment.
Following the final visit, the subjects will be contacted every three months by telephone
to answer basic questions about their health status.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed Informed Consent Form for the study protocol.
2. 18 years of age and older at the time of signing Informed Consent Form.
3. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
4. Histologically or cytologically confirmed de-novo diagnosis of metastatic pancreatic
ductal adenocarcinoma (PDAC).
5. No prior treatment for PDAC.
6. Life expectancy equal to or greater than 3 months.
7. Measurable disease in the abdomen, as defined by RECIST (Response Evaluation
Criteria in Solid Tumors) v1.1.
8. Preferably, tumor accessible for tissue collection. Consent to provide blood and
tumor tissue for exploratory study is highly encouraged. Patients who cannot or are
unwilling to provide tissue or blood for the exploratory study are not excluded from
the study.
- If tumor tissue is available, a formalin-fixed, paraffin-embedded (FFPE) tumor
specimen in a paraffin block (preferred) or approximately 10-15 slides
containing unstained, freshly cut, serial sections should be submitted along
with an associated pathology report prior to study treatment initiation.
- If FFPE specimens described above are not available, any type of specimens
(including fine-needle aspiration, cell pellet specimens [e.g., from pleural
effusion], and lavage samples) are also acceptable. This specimen should be
accompanied by the associated pathology report.
- As mentioned above, if tumor tissue is not available (e.g., depleted because of
prior diagnostic testing), patients are still eligible.
9. Amenable and assigned by the investigator to receive therapy with gemcitabine and
nab- paclitaxel.
10. Adequate hematologic and end-organ function, defined by the following laboratory
test results, obtained within 14 days prior to initiation of study treatment:
1. ANC (absolute neutrophil count) ≥ 1.5 X 109/L (1500/μL) without granulocyte
colony-stimulating factor support within 14 days prior to initiation of study
treatment.
2. Lymphocyte count ≥ 0.5 X 109/L (500/μL).
3. WBC (white blood cell) count ≥2.5x109/L (2500/ μL).
4. Platelet count ≥ 100 X 109/L (100,000/μL) without transfusion.
5. Hemoglobin ≥ 90 g/L (9 g/dL). Patients may be transfused to meet this
criterion.
6. AST (aspartate aminotransferase), ALT (alanine aminotransferase), and ALP
(alkaline phosphatase) ≤ 2.5 X upper limit of normal (ULN), with the following
exceptions:
• Patients with documented liver metastases: AST and/or ALT ≤ 5 X ULN. Patients
with documented liver or bone metastases: ALP ≤ 5 X ULN.
7. Total bilirubin ≤ 1.5 X ULN with the following exception:
• Patients with known Gilbert disease: total bilirubin ≤ 3 X ULN.
8. Creatinine ≤ 1.5 X ULN.
9. Albumin ≥ 25 g/L (2.5 g/dL).
10. For patients not receiving therapeutic anticoagulation: INR/PT (international
normalized ratio/ prothrombin time) or aPTT/PTT (activated partial
thromboplastin time/partial thromboplastin time) ≤ 1.5 X ULN.
11. For patients receiving therapeutic anticoagulation: stable anticoagulation regimen.
12. Negative hepatitis B surface antigen (HBsAg) test at screening
13. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb
at screening accompanied by either of the following:
- Negative total hepatitis B core antibody (HBcAb)
- Positive total HBcAb test followed by a negative (per local laboratory
definition) hepatitis B virus (HBV) DNA (deoxyribonucleic acid) test. The HBV
DNA test must be performed for patients who have a negative HBsAg test, a
negative HBsAb test, and a positive total HBcAb test.
14. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV
antibody test followed by a negative HCV RNA (Ribonucleic acid) test at screening
The HCV RNA test must be performed for patients who have a positive HCV antibody
test.
15. For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception and agreement to refrain from
donating eggs, as defined below:
- Women must remain abstinent or use contraceptive methods with a failure rate of
<1% per year during the treatment period, for 5 months after the final dose of
atezolizumab, for 6 months after the final dose of gemcitabine and for 6 months
after the final dose of nab-paclitaxel. Women must refrain from donating eggs
during this same period.
- A woman is considered to be of childbearing potential if she is post-menarchal,
has not reached a postmenopausal state (≥12 continuous months of amenorrhea
with no identified cause other than menopause),and is not permanently infertile
due to surgery (i.e. removal of ovaries, fallopian tubes, and/or uterus) or
another cause as determined by the investigator (e.g., Müllerian agenesis). The
definition of childbearing potential may be adapted for alignment with local
guidelines or regulations.
- Examples of contraceptive methods with a failure rate of <1% per year include
bilateral tubal ligation, male sterilization, hormonal contraceptive that
inhibit ovulation, hormone-releasing intrauterine devices, and copper
intrauterine devices.
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
post-ovulation methods) and withdrawal are not adequate methods of
contraception. If required per local guidelines or regulations, locally
recognized adequate methods of contraception and information about the
reliability of abstinence will be described in the local Informed Consent Form.
- All patients who are capable of becoming pregnant must take a pregnancy test
which is negative within 72 hours before initiation of study treatment.
16. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive methods, and agreement to refrain from donating sperm, as defined
below:
With a female partner of childbearing potential who is not pregnant, men must remain
abstinent or use a condom plus an additional contraceptive method that together
result in a failure rate of <1% per year during the treatment period and for 6
months after the final dose of gemcitabine and for 6 months after the final dose of
nab-paclitaxel. Men must refrain from donating sperm during this same period.
With a pregnant female partner, men must remain abstinent or use a condom during the
treatment period and for 6 months after the final dose of gemcitabine and for 6
months after the final dose of nab-paclitaxel to avoid exposing the embryo.
The reliability of sexual abstinence should be evaluated in relation to the duration
of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and
withdrawal are not adequate methods of contraception. If required per local
guidelines or regulations, locally recognized adequate methods of contraception and
information about the reliability of abstinence will be described in the local
Informed Consent Form.
17. Able to operate the NovoTTF-200T device independently or with the help of a
caregiver.
Exclusion Criteria:
1. Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases.
Asymptomatic patients with treated CNS lesions are eligible, provided that all of
the following criteria are met:
- The patient has no history of intracranial hemorrhage or spinal cord
hemorrhage.
- The patient has not undergone stereotactic radiotherapy within 7 days prior to
initiation of study treatment, whole-brain radiotherapy within 14 days prior to
initiation of study treatment, or neurosurgical resection within 28 days prior
to initiation of study treatment.
- The patient has no ongoing requirement for corticosteroids as therapy for CNS
disease.
- Anticonvulsant therapy at a stable dose is permitted.
2. History of leptomeningeal disease.
3. Uncontrolled tumor-related pain
- Patients requiring pain medication must be on a stable regimen at study entry.
- Symptomatic lesions (e.g., bone metastases or metastases causing nerve
impingement) amenable to palliative radiotherapy should be treated prior to
treatment initiation. Patients should be recovered from the effects of
radiation. There is no required minimum recovery period. Palliative
radiotherapy is permitted, provided it does not interfere with the assessment
of tumor target lesions (e.g., the lesion to be irradiated must not be the only
site of measurable disease).
- Asymptomatic metastatic lesions that would likely cause functional deficits or
intractable pain with further growth (e.g., epidural metastasis that is not
currently associated with spinal cord compression) should be considered for
loco-regional therapy, if appropriate, prior to treatment initiation.
4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage
procedure (i.e., more than one time per month).
• Patients with indwelling catheters (e.g. PleurX®) are allowed
5. Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12
mg/dL, or corrected calcium>ULN)
6. Active or history of autoimmune disease, including but not limited to myasthenia
gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease, vascular thrombosis associated with
antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome,
Guillain-Barré syndrome or multiple sclerosis (see Appendix 2 for a more
comprehensive list of autoimmune diseases and immune deficiencies), with the
following exceptions:
- Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid-replacement hormone may be eligible for this study
- Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen
are eligible for this study
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g. patients with psoriatic arthritis would
be excluded) are permitted provided that they meet the following conditions:
- Rash must cover <10% of body surface area
- Disease is well controlled at baseline and only requiring low-potency
topical steroids
- No acute exacerbations of underlying condition within the last 12 months
requiring treatment with either psoralen plus ultraviolet A radiation,
methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or
high-potency or oral steroids
7. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest computed tomography (CT) scan.
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
8. Positive human immunodeficiency (HIV) test at screening or at any time prior to
screening.
9. Current treatment with anti-viral therapy for HBV (hepatitis B virus).
10. Active tuberculosis.
11. Severe infection within 4 weeks prior to initiation of study treatment, including
but not limited to hospitalization for complications of infection, bacteremia, or
severe pneumonia, or any active infection that, in the opinion of the investigator,
could impact patient safety.
12. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of
study treatment, or anticipation of need for such a vaccine during atezolizumab
treatment or within 5 months after the final dose of atezolizumab.
13. Prior allogeneic stem cell or solid organ transplantation.
14. History of malignancy within 5 years prior to initiation of study treatment, with
the exception of the cancer under investigation in this study and malignancies with
a negligible risk of metastasis or death (e.g., 5-year OS (overall survival) rate >
90%) treated with an expected curative outcome, such as adequately treated carcinoma
in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer,
ductal carcinoma in situ, or Stage I uterine cancer.
15. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins.
16. Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within
3 months prior to initiation of study treatment, unstable arrhythmia, or unstable
angina.
17. Major surgical procedure within 28 days prior to initiation of study treatment or
anticipation of need for a major surgical procedure during the course of the study.
For patients undergoing laparoscopy (without resection) for PDAC, within 14 days
prior to initiation of study treatment.
18. Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug or
device, may affect the interpretation of the results, or may render the patient at
high risk from treatment complications.
19. History of any psychiatric condition that might impair patient's ability to
understand or comply with the requirements of the study or to provide consent.
20. Concurrent anti-tumor therapy beyond gemcitabine and nab-paclitaxel.
21. Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
including anti-CTLA-4 (cytotoxic T lymphocyte antigen-4), anti PD-1 (programmed cell
death protein 1), and anti PD-L1 (programmed death-ligand 1) therapeutic antibodies.
22. Treatment with systemic immunostimulatory agents (including but not limited to
interferons or interleukin 2) within 4 weeks or 5 half-lives of the drug, whichever
is longer, prior to initiation of study treatment.
23. Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti
- tumor necrosis factor-α [TNF-α] agents) within 2 weeks prior to initiation of
study treatment, or anticipation of need for systemic immunosuppressive medication
during study treatment, with the following exceptions:
- Patients who received acute, low-dose, systemic immunosuppressant medications
or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48
hours of corticosteroids for a contrast-agent allergy) are eligible for the
study. It is recommended that patients requiring use of steroids for a
contrast-agent allergy will undergo chest CT without contrast-agent and abdomen
and pelvis MRI (Magnetic Resonance Imaging) with Gadolinium.
- Patients who received mineralocorticoids (e.g., fludrocortisone), inhaled or
low-dose corticosteroids for COPD (chronic obstructive pulmonary disease) or
asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal
insufficiency are eligible for the study.
24. Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 28 days prior to initiation of study treatment.
25. Implantable electronic medical devices in the torso, such as pacemakers.
26. Known allergies to medical adhesives or hydrogel, or to one of the chemotherapies
used in this study or biopharmaceuticals produced in Chinese hamster ovary cell
products or to any component of the atezolizumab formulation.
27. Treatment with therapeutic oral or IV (intravenous) antibiotics within 2 weeks prior
to initiation of study treatment.
Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract
infection or chronic obstructive pulmonary disease exacerbation) are eligible for
the study.
28. Pregnant or breast-feeding, or intending to become pregnant during study treatment
or within 5 months after the final dose of atezolizumab or within 6 months after the
last dose of gemcitabine or within 6 months after the last dose of nab-paclitaxel,
whichever is later.
29. Unable to follow the protocol for medical, psychological, familial, geographic or
other reasons.
30. Admitted to an institution by administrative or court order.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Teresa Macarulla Mercade
Phone:
34 (93) 274 6085
Email:
tmacarulla@vhebron.net
Facility:
Name:
University Hospital Foundation Jimenez Diaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Angela Lamarca Lete
Phone:
34 951 504800
Email:
angela.lamarca@quironsalud.es
Contact backup:
Last name:
1
Facility:
Name:
Clara Campal Comprehensive Cancer Center (CIOCC)
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Antonio Cubillo Gracian
Phone:
34 91 756 7800
Email:
acubillo@hmhospitales.com
Facility:
Name:
Regional University Hospital of Malaga
Address:
City:
Málaga
Zip:
29010
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Inmaculada Ales
Phone:
34 951308129
Email:
inales@hotmail.com
Facility:
Name:
University Clinic of Navarra - Pamplona
Address:
City:
Pamplona
Zip:
31008
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Mariano Ponz-Sarvise
Phone:
34 948 255 400
Email:
mponz@unav.es
Start date:
August 28, 2023
Completion date:
August 2026
Lead sponsor:
Agency:
NovoCure GmbH
Agency class:
Industry
Source:
NovoCure Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06390059
