RAmucirumab Combined wIth Standard Nab-paclitaxel and Gemcitabine as First-line Chemotherapy in Patients With Advanced Pancreatic Adenocarcinoma

NCT03745430 | Completed Phase 1

• 2 other identifiers: HE3/162017-004792-30
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 13

Brief Summary

RACING (RAmucirumab Combined wIth standard Nab-paclitaxel and Gemcitabine as first-line chemotherapy in patients with advanced pancreatic adenocarcinoma) trial is a Greek, investigator-initiated, single-arm, open-label phase Ib-II study. Patients with advanced cytologically or histologically proven pancreatic adenocarcinoma will be treated with a combination of Ramucirumab with Nab-paclitaxel and Gemcitabine (for a maximum of 8 cycles followed by Ramucirumab maintenance) until disease progression or excessive Adverse Events (AEs) or Investigator's decision or patient's refusal of further treatment or death, whichever comes first.

Conditions

Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Assessment of safety by identifying the Recommended Dose (RD) of the combination of Ramucirumab with Nabpaclitaxel and Gemcitabine.

  From enrollment up to 90 days after the last administration of any investigational product

• Phase II: Overall Response Rate is defined as the proportion of patients with confirmed Complete Response or confirmed Partial Response as best overall response to treatment, based on RECIST v. 1.1 guidelines in the considered analysis population.

  Up to 33 months

Secondary Outcomes (16)

• Overall survival (OS)

  Up to 33 months

• Progression-free survival

  Every 8 weeks until month 8 and then every 12 weeks, up to 33 months

• Phase I:Toxicity profile of the combination during the first 2 cycles of therapy

  From the first administration of study treatment and up to week 8 (during the first 2 cycles of the treatment, each cycle is 28 days)

• Phase II: Number of participants with Serious and Non-Serious Adverse Events graded according to National Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0

  From enrollment up to 33 months.

• Investigation of SPARC gene mutation, m-RNA and protein expression

  At baseline, in cycles 1 and 3 (each cycle is 28 days), at maintenance therapy and at the date of first documented progression up to 33 months

Study Arms (1)

Ramucirumab+Nab-paclitaxel+Gemcitabine

EXPERIMENTAL

Nab-paclitaxel and Gemcitabine will be administered on days 1, 8 and 15 every 4 weeks for a maximum of 8 cycles.

Drug: Ramucirumab

Interventions

Ramucirumab DRUG

8 mg/kg (days 1 and 15, q4w) until disease progression

Also known as: Cyramza

Ramucirumab+Nab-paclitaxel+Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent
• Histologically or cytologically proven pancreatic adenocarcinoma.
• Metastatic or locally advanced unresectable disease confirmed clinically/radiologically by CT-scan or MRI (Magnetic Resonance Imaging)
• No prior therapy for metastatic disease.
• At least one measurable or evaluable lesion as assessed by CT-scan or MRI according to RECIST v1.1
• Age 18 years,
• ECOG Performance status (PS) 0-1
• The patient has adequate hepatic function as defined by a total bilirubin 1.5 mg/dL (25.65 μmol/L), and aspartate transaminase (AST) and alanine transaminase (ALT) 2.5 times the upper limit of normal (ULN; or 5.0 times the ULN in the setting of liver metastases)
• Female patients must commit to using reliable and appropriate methods of contraception during the trial until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another reliable contraceptive method during the trial until at least 6 months after the end of study treatment.
• Patients must have a low or intermediate risk of arterial or venous thrombotic events (Khorana risk score 0-2). Patients at a high VTE risk (Khorana RS3) are eligible if they receive LMWH prophylaxis (Appendix D).

You may not qualify if:

• The patient has pancreatic cancer with histology other than adenocarcinoma
• Prior therapy for metastatic disease. Adjuvant Gemcitabine is permitted if 6 or more months have elapsed from last cycle to date of relapse.
• Exclusive presence of bone metastasis only
• Concomitant unplanned antitumor therapy
• Treatment with any other investigational medicinal product within 28 days prior to study entry
• Other serious and uncontrolled non-malignant chronic disease
• The patient has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
• The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal antiinflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325mg/day) is permitted.
• The patient has experienced grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis within 3 months prior to first dose of protocol therapy.
• Other concomitant or previous malignancy
• The patient has symptomatic congestive heart failure (CHF; New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia
• Bowel obstruction
• The patient has a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation.
• Palliative radiation therapy within 4 weeks prior to registration
• The patient has a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy.

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead
• Eli Lilly and Company: collaborator
• Celgene Corporation: collaborator

Study Sites (13)

Agios Savvas Anticancer Hospital

Athens, Attica, 11522, Greece

Location

Aretaieio Hospital

Athens, Attica, 11528, Greece

Location

"Attikon" University Hospital

Chaïdári, Attica, 12462, Greece

Location

Metropolitan General Hospital

Cholargós, Attica, 15562, Greece

Location

Metropolitan Hospital

Neo Faliro, Attica, 18547, Greece

Location

Ygeia Hospital

Psychikó, Attica, 15123, Greece

Location

3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

Athens, Nea Kifisia, 14564, Greece

Location

Agii Anargiri Cancer Hospital

Athens, Nea Kifisia, 14564, Greece

Location

University Hospital of Patra

Rio, Patra, 26504, Greece

Location

EUROMEDICA General Clinic of Thessaloniki

Thessaloniki, Thessaloniki, 54645, Greece

Location

Haematology- Oncology Section, Dept of Clinical Therapeutics, General Hospital of Athens "Alexandra"

Athens, 11528, Greece

Location

Department of Medical Oncology, Ioannina University Hospital

Ioannina, 45500, Greece

Location

General University Hospital of Larissa

Larissa, 41110, Greece

Location

MeSH Terms

Interventions

Ramucirumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• George Papaxoinis, MD

  2nd Medical Department, Agios Savvas Anticancer Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 19, 2018
• Study Start: January 29, 2019
• Primary Completion: June 17, 2022
• Study Completion: April 23, 2023
• Last Updated: May 24, 2023

Record last verified: 2023-05

Locations

GR (13)