| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Cancer Patients with Solid Tumors with Chemotherapy Induced Anemia |
|
| E.1.1.1 | Medical condition in easily understood language |
| Condition of low levels of red blood cells brought on by chemical treatment for cancer causing symptoms such as tiredness, lethargy, weakness, dizzy spells and feeling faint |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10002034 |
| E.1.2 | Term | Anaemia |
| E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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| 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 |
| To determine the safety, tolerability and pharmacokinetics of two multiple oral dose levels of 5-aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) given in cancer patients with solid tumors with chemotherapy induced anemia (CIA). |
|
| E.2.2 | Secondary objectives of the trial |
| To assess pharmacodynamic responses of orally 5-ALA and SFC administered to cancer patients with solid tumors with CIA. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adult patients between 18 and 80 years old (inclusive) at Screening, with active solid tumors.
2. Received chemotherapy within 6 weeks of the first dosing of study drug for this trial.
3. Patients who are anticipated to receive 2 or more additional chemotherapy treatments during the study duration (following the first dosing and before the final dosing).
4. Anemia that is thought to be due to chemotherapy (Screening hemoglobin [Hb] between 9.0 g/dL and 11.0 g/dL, inclusive AND at least 1 g/dL less than the Hb prior to starting the current course of chemotherapy AND Hb ≥11 g/dL at the time of starting that course of
chemotherapy). Patients should not have been anemic Hb <11 g/dL at time of starting the current course of chemotherapy.
5. Adequate renal function and adequate hepatic function (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] ≤2.5 x upper limit of normal [ULN]); serum creatinine ≤1.5 x ULN; total bilirubin ≤1.5 x ULN these results should be at less than Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (patients with Gilbert’s Syndrome may be included).
6. Patients should not be iron deficient (Fe/total iron binding capacity [TIBC] x 100 should be over 15%).
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1 at the time of Screening.
8. Male and female patients must practice effective contraception and females of childbearing potential must have a negative pregnancy test prior to enrolment.
9. Patient is informed of the nvestigational nature of this study and has given written, witnessed informed consent.
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| E.4 | Principal exclusion criteria |
1. Patients with non solid, bone marrow based tumors.
2. Patients with renal cancer or inflammatory breast cancer.
3. Patients who have received any red blood cell (RBC) transfusion within 28 days before randomization.
4. Patients diagnosed with hemochromatosis.
5. Patients who have received any erythropoiesis-stimulating agents (ESA) treatment within 3 months prior to Screening.
6. Patients who have received a bone marrow or stem cell transplant in the 6 months prior to Screening or planned during the study, or with planned stem cell harvest of bone marrow during the study.
7. Patients with a history of, or active pure red cell aplasia (PRCA).
8. Other underlying disorder, which could cause anemia (e.g., hematologic disorder, iron or vitamin B12 deficiency, or gastrointestinal bleeding) as detected with ongoing diagnostic tests or with obvious clinical evidence.
9. Planned elective surgery during the study where significant blood loss is expected.
10. Planned radiation treatment during the study.
11. Active, unstable systemic or chronic infection.
12. Severe, unstable, active chronic inflammatory disease (e.g. ulcerative colitis, peptic ulcer disease, rheumatoid arthritis).
13. Uncontrolled hypertension (diastolic blood pressure >100 mmHg).
14. Unstable angina or uncontrolled cardiac arrhythmia.
15. History of Cerebro-vascular Accident (CVA), Transient Ischemic Attack (TIA), Acute Coronary Syndrome (ACS) including unstable angina and myocardial infarction or other arterial thrombosis within 6 months before study enrolment.
16. History of Deep Venous Thrombosis (DVT) or Pulmonary Embolus (PE) within 12 months before study enrolment. Prior superficial thrombophlebitis is not an exclusion criterion.
17. Known positive human immunodeficiency virus (HIV) test or acquired immunodeficiency syndrome (AIDS) status.
18. Positive serology for hepatitis B surface antigen or hepatitis C antibody.
19. Patient has known sensitivity to any erythropoietic agents, the investigational products (including iron) or its excipients to be administered during this study.
20. Any gastrointestinal disorder or past gastrointestinal surgery that could alter the absorption of orally administered compounds.
21. Patients who are unwilling to refrain from sun tanning or other bright light exposure for the duration of the study.
22. Patients who are pregnant or breast feeding.
23. Patients who are deemed otherwise not suitable for enrolment by the Investigator.
24. Patients with previous history of photosensitivity.
25. Patients who have acute or chronic types of porphyria or family history of porphyria.
26. Patients with hypersensitivity to 5-ALA or porphyrins.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
-Safety and Tolerability Assessments:
1. Adverse Events
2. Vital Signs: Blood presure and pulse rate and oral body temperature
3. 12-Lead Electrocardiogram
4. Clinical Laboratory Evaluations: Clinical Chemistry, Hematology, Urinalysis.
5. Glomerular Filtration Rate
6. Fecal Occult Blood
7. Physical Examination
8. Body Weight
9. Functional Assessment of Cancer Therapy Anemia (FACT-An)
-Pharmacokinetics
Clinical Laboratory analysis
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|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Safety and Tolerability
1.Scr, w0,w1, w2, w4, w6, w8, Post.
2.
-Blood presure and pulse rate: Scr, w0-predose to postdose, w1, w2, w4, w6, w8, Poststudy.
-Oral body temperature: Scr, w4, Poststudy.
3. Scr, w4, Poststudy.
4.
- Clinical Chemistry: Scr, w0 predose, w2, w4, w6, w8, Poststudy.
- Hematology: Scr, w0 predose, w1, w2, w4, w6, w8, Poststudy.
- Urinalysis: Scr, w2, w4, w8, Poststudy.
5.W0-predose,w2, w4, w6, w8, Poststudy.
6.Scr.
7.Scr, w4,Poststudy.
8.Scr, w0, w1, w2, w4, w6, w8, Poststudy.
9. w0-predose, w2, w4, w6, w8.
-Pharmacokinetics
Clinical Laboratory analysis
-5-ALA in plasma: Scr, w0 (Day 1) predose to 8h postdose.
-5-ALA urine: day 1 predose to postdose, w4, w8, Poststudy.
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| E.5.2 | Secondary end point(s) |
-Pharmacodynamics. Clinical Laboratory analysis
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Pharmacodynamics. Clinical Laboratory analysis:
-Blood sampling for porphyrin, HO-1: Scr, Day 1 predose to postdose.
- Urine for porphyrin, porphobilinogen: Day 1 predose to postdose, w4, w8, Poststudy.
- Blood sampling for iron, TIBC, UIBC, ferritin, transferrin: Scr, w0-predose, w4, w8, Poststudy.
Exploratory Biomarkers: Hepcidin, Erythropoietin, eGFR, Interleukin-6, TNF alpha: w0-predose, w2, w4, w6, w8,
Poststudy. |
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| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| 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 | No |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
| The final scheduled visit for the last patient. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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