E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent or Progressive KRAS Wild Type Colorectal Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010030 |
E.1.2 | Term | Colorectal cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine the effects of Imprime PGG in combination with cetuximab compared to cetuximab alone on PFS in subjects with recurrent or progressive KRAS WT colorectal cancer. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to determine the following in subjects treated with Imprime PGG in combination with cetuximab compared to cetuximab alone:
• Progression free survival (PFS)
• Rates of complete response (CR), partial response (PR), and overall response (CR + PR)
• Safety of dosing regimen
• Pharmacokinetic (PK) profile of Imprime PGG and cetuximab
• Changes in Quality of Life
Exploratory objectives are to determine the plasma levels of cytokines, chemokines and other factors associated with innate immune activation may be measured by immune assays (i.e Luminex® technology). Specific examples of immune biomarkers that may be measured in this study include, but are not limited to, components of the complement cascade such as C5a and cytokines and chemokines such as macrophage inflammatory protein 1, monocyte chemotactic protein 1, Interleukin (IL)-10, VEGF, and IL-12. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Is ≥18 years old;
2. Has recurrent or metastatic carcinoma of the colon or rectum with documented histological or cytological confirmation;
3. Must be KRAS WT;
• In France – Must be KRAS WT (On exon 2);
4. Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1;
5. Has never received cetuximab or panitumumab, and has not received any treatment for colorectal cancer within 30 28 days prior to the first dose of study treatment under this protocol;
6. Has an Eastern Cooperative Oncology Group (ECOG) score of 0-1, with a life expectancy of 3 months;
7. Has received prior chemotherapy threatment for colorectal cancer as specified below:
• In Germany- prior therapy with an oxaliplatin based regimen and an irinotecan based regimen (irinotecan regimen not required if irinotecan is contraindicated for that subject)
• In France- Has received prior chemotherapy regimens for metastatic colorectal cancer with oxaliplatin and fluorpyrimidines (5FU/FA or capecitabine) with or without bevacizumab; irinotecan alone or in association with fluorpyrimidines (5FU/FA or capecitabine) with or without bevacizumab
• In All Other Countries- has received at least 2 prior chemotherapeutic regimens for colorectal cancer;
8. Has adequate bone marrow reserve as evidenced by:
a. Absolute neutrophil count greater or equal to 1,500/μL
b. Platelets greater or equal to 100,000/μL;
9. Has adequate renal function as evidenced by serum creatinine less than or equal to 2.5 times the upper limit of normal (ULN) for the reference lab;
10. Has adequate hepatic function as evidenced by:
a. AST less than or equal to 3 times ULN for the reference lab (less than or equal to 5 times ULN for subjects with known hepatic metastases)
b. ALT less than or equal to 3 times ULN for the reference lab (less than or equal to 5 times ULN for subjects with known hepatic metastases)
c. Bilirubin less than 1.5 mg/dL, or direct bilirubin less than 1.0 mg/dL
d. Serum Albumin greater than 3.0 gm/dL
11. Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Independent Ethics Committee (IRB/IEC); and
12. If the subject is a woman of childbearing potential or a fertile man, he/she must agree to use an effective form of contraception during the study and for 60 days following the last dose of study drug (an effective form of contraception is abstinence, a hormonal contraceptive, or a double-barrier method).
|
|
E.4 | Principal exclusion criteria |
1. Has a known hypersensitivity to cetuximab, murine proteins, or any component of cetuximab;
2. Has a known hypersensitivity to baker’s yeast or has an active yeast infection;
3. Has had previous exposure to Betafectin® or Imprime PGG;
4. Has an active, uncontrolled infection;
5. Has known untreated or symptomatic brain metastases;
6. Had a second malignancy within the previous 5 years, except for basal cell carcinoma, cervical intra-epithelial neoplasia, or treated prostate cancer with a prostate-specific antigen (PSA) of 2.0 ng/mL;
7. Has known human immunodeficiency virus or acquired immune deficiency syndrome, hepatitis B, hepatitis C, connective tissue disease, or other clinical diagnosis, ongoing or intercurrent illness that in the Investigator’s opinion should preclude the subject from participation;
8. If female, is pregnant or breast-feeding;
9. Is receiving concurrent standard and/or investigational anti-cancer therapy or has received such therapy within a period of 28 days prior to the first scheduled day of dosing (investigational therapy is defined as treatment for which there is currently no regulatory-authority-approved indication); or
10. Has previously received an organ or progenitor/stem cell transplant.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is Progression Free Survival which is defined as the time from the date of the first dose of study drug until the first date on which progressive disease is determined, or death due to any cause is documented, and will be censored at the date of the last contact for subjects who are lost-to-follow-up or who are alive at the time of analysis. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Quarterly after completion of study drug. |
|
E.5.2 | Secondary end point(s) |
• Progression free survival (PFS)
• Rates of complete response (CR), partial response (PR), and overall response (CR + PR)
• Safety of the dosing regimen
• Changes in Quality of Life |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 6 weeks from Cycle 1/Day 1 through Week 36, then every
8 weeks through 1 year from Cycle 1/Day 1. Finally, evaluation will be performed every 12 weeks thereafter.
• Progression free survival (PFS)
• Rates of complete response (CR), partial response (PR), and overall response (CR + PR)
• Changes in Quality of Life
Weekly:
• Safety of the dosing regimen
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |