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RP72 Monotherapy and in Combination With Gemcitabine in Patients With Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04338763
Recruitment Status : Not yet recruiting
First Posted : April 8, 2020
Last Update Posted : October 19, 2020
Sponsor:
Collaborator:
Amarex Clinical Research
Information provided by (Responsible Party):
Rise Biopharmaceuticals, Inc.

Brief Summary:

This is a Phase I, multi center study to evaluate the safety and efficacy and determine the maximum tolerated dose (MTD) of RP72 as monotherapy and RP72 in combination with Gemcitabine in patients with pancreatic cancer.

The study has two arms:

Arm A: RP72 monotherapy

Arm B: RP72 in combination with Gemcitabine

Both treatment arms will follow a standard 3+3 design. Up to 48 adult patients with pancreatic cancer will be enrolled in this study.


Condition or disease Intervention/treatment Phase
Pancreatic Cancer Pancreatic Cancer Non-resectable Pancreatic Cancer Metastatic Drug: RP72 Drug: Gemcitabine Phase 1

Detailed Description:

RP72 (Rise Prot-72) is a small molecular weight protein which directly binds to CXCR1 and CXCR2, which are the receptors of CXCL8 [Interleukin 8 (IL-8) or chemokine (C-X-C motif) ligand 8] and ELR-CXC chemokine. Therefore, RP72 can inhibit the binding of CXCL8 to its receptors CXCR1/2 and further block CXCL8-mediated signal transduction. Nonclinical studies have demonstrated that RP72 binds to the receptors of CXCL8 and blocks activation of CXCL8-mediated signaling transduction pathways, which decreases proliferation of susceptible tumor cells, especially the pancreatic cancer cells.

In this Phase I study, RP-72 will be used as monotherapy or in combination with gemcitabine in adult patients with pancreatic cancer. The study aims to to evaluate the safety and efficacy, and to determine the MTD and recommended Phase II dose of RP72 monotherapy and RP72 in combination with Gemcitabine in patients with Pancreatic Cancer.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study to Evaluate the Safety and Efficacy of RP72 Monotherapy and in Combination With Gemcitabine in Patients With Pancreatic Cancer
Estimated Study Start Date : November 1, 2020
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A: RP72 monotherapy Drug: RP72
RP72 is formulated as a sterile lyophilized powder which is reconstituted in sterile water for injection (WFI) prior to administration. IV injection of RP72 will be administered thrice weekly in the first 28-day treatment cycle (Cycle 1). RP72 will continue to be administered thrice weekly for 4 weeks for Cycle 2 and each subsequent 28-day treatment cycle.
Other Name: Rise Prot-72

Experimental: Arm B: RP72 in combination with Gemcitabine Drug: RP72
RP72 is formulated as a sterile lyophilized powder which is reconstituted in sterile water for injection (WFI) prior to administration. IV injection of RP72 will be administered thrice weekly in the first 28-day treatment cycle (Cycle 1). RP72 will continue to be administered thrice weekly for 4 weeks for Cycle 2 and each subsequent 28-day treatment cycle.
Other Name: Rise Prot-72

Drug: Gemcitabine
Gemcitabine is an anti-cancer chemotherapy drug. IV infusion of Gemcitabine will be administered once weekly in the first 28-day treatment cycle (Cycle 1). Gemcitabine will continue to be administered once weekly for the first 3 weeks and then one week rest in Cycle 2 and each subsequent 28-day treatment cycle.




Primary Outcome Measures :
  1. Determination of the maximum tolerated dose (MTD) and the recommended dose for phase II of RP72 monotherapy and RP72 in combination with Gemcitabine [ Time Frame: Over the 28 day treatment period ]
    The MTD is defined as 1 dose level (cohort) below the dose in which dose limiting toxicities (DLTs) were observed in ≥ 33% of the participants.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years (in certain territories, the minimum age requirement may be higher, e.g. age ≥ 20 years in Taiwan)
  2. Written informed consent
  3. Patient must meet one of the following criteria based on:

    Arm A (RP72 monotherapy): Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic cancer that has progressed on (or intolerant of) one or more standard treatment regimen(s) or for which no effective therapy is available. Note: Prior exposure to gemcitabine as a single agent or in combination with other agents (as part of multi-agent chemotherapy regimen) is acceptable.

    Or

    Arm B (RP72 in combination with Gemcitabine): Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic cancer that has progressed on (or intolerant of) one or more standard treatment regimen(s) and is expected (or currently receiving) standard treatment with gemcitabine.Note: Patients who have already started on gemcitabine need to have no evidence of disease progression at the time of screening in order to be eligible for the study.

    Note: The definition of unresectability will follow the criteria of NCCN guidelines (Carroll et al. version 2.2016, PANC-B)

  4. Fasting blood glucose <160 mg/dl, prior to study enrollment. (For higher values, blood glucose may be controlled by dietary intervention, oral hypoglycemics and/ or insulin prior to enrollment)
  5. Estimated life expectancy of ≥12 weeks
  6. Adequate hematologic and end-organ function
  7. Measurable / assessable disease according to RECIST v.1.1
  8. ECOG performance status 0 or 1
  9. Subjects who are eligible and able to participate in the study and accept to enter the study by signing written informed consent forms
  10. Patients are recovered from toxicities from prior systemic therapies and have adequate hematopoietic, liver and renal function at screening and before using study medication

    • Haemoglobin ≥ 8 g/dL
    • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
    • Absolute lymphocyte count ≥ 1000/mm3,
    • Platelets ≥ 80,000 /mm3
    • Total white blood cell (WBC) ≥ 3,000 cells /mm3
    • Coagulation tests (prothrombin time [PT], activated partial thromboplastin time [aPTT], International Normalized Ratio [INR]) < 1.5×ULN,
    • Total bilirubin ≤ 1.5×ULN,
    • Aspartate Aminotransferase (AST)/Serum Glutamic Oxaloacetic Transaminase(SGOT) and/or Alanine Aminotransferase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT) ≤ 3 x ULN (or ≤ 5×ULN if liver metastases are present
    • Albumin > 2.5 g/dL
    • Creatinine Clearance (CrCl) > 60 mL/min[Cockcroft-Gault equation]
  11. All male subjects and female subjects with child-bearing potential (between puberty and 2 years after menopause) should use appropriate contraception method(s) for at least 4 weeks after RP72 treatment shown below.

    • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception).
    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
    • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
    • Combination of any two of the following (a+b or a+c, or b+c):

      1. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
      2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
      3. Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.

Exclusion Criteria:

  1. Patients with endocrine or acinar pancreatic carcinoma.
  2. Patients who present with jaundice; Note: Patients who present with jaundice will be allowed to enroll after control with temporary or permanent internal/external drainage.
  3. Any severe infection, uncontrolled systemic disease (e.g., cardiopulmonary insufficiency, fatal arrhythmias, hepatitis, etc) that, in the opinion of the investigator, may impair the patient's tolerance of study treatment.
  4. Major surgery within 4 weeks from the first dose of the study drug
  5. Female subjects that are lactating, pregnant, or planned to become pregnant
  6. Investigational medicinal product within 4 weeks from the first dose of the study drug
  7. Concurrent use of immunosuppressive medication. The following are exceptions to this criterion:

    • Intranasal, inhaled, topical steroids, or local steroid injections
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
    • Steroids as premedication for hypersensitivity reactions
  8. Active autoimmune diseases requiring treatment or a history of autoimmune disease.
  9. Documented HIV history
  10. Active hepatitis B infection requiring acute therapy. Note: Subjects infected by the hepatitis B virus will be eligible for the study if they have no signs of hepatic decompensation and meet the liver function tests eligibility criteria.
  11. Chronic active hepatitis C infection as manifest by positive anti-HCV antibody and positive HCV RNA assay at the time of screening
  12. History of malignancy other than pancreatic cancer < 3 years prior to enrolment, except non-melanoma skin cancer or carcinoma in situ of the cervix treated locally
  13. Known hypersensitivity to any component of the RP72 and/or Gemcitabine formulations (including kanamycin or other aminoglycosides)
  14. Subjects that received radiation to ≥ 25% of their bone marrow within 4 weeks of the first dose of study drug.
  15. Evidence of central nervous system (CNS) metastasis. Note: Subjects who have a central nervous system metastasis that has been treated, stable and has not needed treatment for at least 4 weeks at the time of screening will be allowed to enroll in the study.
  16. Subjects that have on-going moderate to severe organ impairment, other than the study indication, that may confound the efficacy evaluation, safety evaluation or usage of standard chemotherapy
  17. Corrected QT interval (QTc) ≥ 470 msec on the 12-lead ECG

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04338763


Contacts
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Contact: Kush Dhody, MBBS, MS, CCRA (301) 956-2536 kushd@amarexcro.com

Sponsors and Collaborators
Rise Biopharmaceuticals, Inc.
Amarex Clinical Research
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Responsible Party: Rise Biopharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04338763    
Other Study ID Numbers: RP-72-002
First Posted: April 8, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rise Biopharmaceuticals, Inc.:
Pancreatic Cancer
RP72
Rise Prot-72
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs