Overview

Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PROMITIL) in Cancer Patients With Solid Tumors.

Status:
Completed
Trial end date:
2018-06-01
Target enrollment:
0
Participant gender:
All
Summary
This is a Phase I, multi-center, Dose-Escalating, Safety Study of an Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, PROMITIL) in Cancer Patients with Solid Tumors. The study comprised of: Escalated cohorts A-H: 27 male or female participants, ages 18-80, BMI 18-36 diagnosed with inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have failed to respond to standard therapy or for whom no standard therapy is available. Eligible subjects will be assigned, successively in order of accrual, to one of eight cohorts, to receive escalating doses of intravenously infused PROMITIL. PROMITIL will be administered as an intravenous infusion. Dose escalation will only proceed in the absence of dose-limiting toxicity (DLT). For this purpose, each cohort will only begin its first cycle of PROMITIL when the cohort preceding it has successfully completed its first 4-week cycle without any signs of DLT. Expanded cohort: 17 adult patients with metastatic CRC. The purpose of this expanded cohort is to further evaluate the safety of Promitil and to search for signs of antitumor activity of Promitil in this specific patient population. Combination Cohort (Promitil concomitantly with Capecitabine): 23 adult patients with metastatic CRC. Triple combination Cohort: 13 additional subjects with metastatic CRC, received combination of Promitil concomitantly with Bevacizumab (5 mg/kg) on day 1 of a 28 day cycle and Capecitabine on days 1-14 of a 28 day cycle. 3 weekly cohort- 9 subjects with metastatic CRC will receive Promitil and Bevacizumab (7.5 mg/kg) on day 1 of a 21 day cycle.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Lipomedix Pharmaceuticals Inc.
Treatments:
Bevacizumab
Capecitabine
Mitomycin
Mitomycins
Criteria
Inclusion Criteria:

1. Patients diagnosed with inoperable, recurrent or metastatic malignant solid tumors,
deemed incurable, and who have either:

- Failed to respond to standard therapy or

- For whom no standard therapy is available or

- Refuse to receive standard therapies

2. Histologically or cytologically confirmed diagnosis of solid tumor on file.

3. Age 18-80 years

4. BMI: 18-36

5. ECOG Performance Status ≤ 2

6. Estimated life expectancy of at least 3 months

7. Adequate bone marrow function (an absolute neutrophil count ≥1500/mm3, hemoglobin ≥9.5
g/dl, HgbA1C≤7%, and a platelet count ≥100,000/mm3(

8. Adequate liver function (serum bilirubin ≤2.0 mg/100 ml; alanine aminotransferase ≤2×
ULN)

9. Adequate renal function (serum creatinine ≤1.5 mg/100 ml or creatinine clearance ≥45
ml/min/1.73m2)

10. No prior intravenous treatment with Mitomycin-C either alone or in combination

11. No other myelosuppressive treatment within 4 weeks before start of the study drug.

12. No other anti-cancer treatment within 2 weeks before start of the study drug

13. No prior extensive radiotherapy (e.g., whole pelvis total neuroaxis or greater than
50% of neuroaxis, whole abdomen, whole body or half-body) or bone marrow
transplantation with high dose chemotherapy and/or total body irradiation.
Re-irradiation of a field in abdomen/pelvis will be considered as extensive
radiotherapy, excluding such patients from the study.

14. Women of child bearing potential practicing an acceptable method of birth control.

15. Understanding of study procedures and willingness to comply for the entire length of
the study and to give written informed consent.

16. Additional criteria only for the Expanded Cohort and both Combination cohorts:
Patients with histologically or cytologically confirmed recurrent and/or metastatic
measurable or nonmeasurable CRC, with tissue or cytological diagnosis of cancer on
file.

17. Additional criteria only for the Expanded Cohort and both Combination cohort: Patients
who demonstrated either progression or intolerance when treated with irinotecan and
fluopyrimidine-based chemotherapy, and, in the case of K-ras wild type tumors,
anti-EGFR antibodies (Cetuximab, Panitumumab). Prior treatment with oxaliplatin or
bevacizumab is allowed but not required.

18. Additional criteria only for the Expanded Cohort and both Combination cohorts: A ≥28
day treatment-free interval between last chemotherapeutic treatment and first
treatment with Promitil, with the exception of Capecitabine and biological therapies,
where 14-day treatment-free intervals suffice. this is also relevant for patients in
the Combination Cohort that are currently taking Capecitabine prior to enter the
study).

19. Additional criteria for the Triple Combination Cohort with bevacizumab only: Prior
exposure to oxaliplatin should have terminated at least 6 months before start of
PROMITIL, whether given as adjuvant therapy or as therapy for metastatic disease.

20. Additional criteria for the triple Combination Cohort with bevacizumab only: A ≥ 28
day treatment-free interval from last bevacizumab treatment

Exclusion Criteria:

1. Known hypersensitivity to the study drug or to any of its components

2. CHF (NYHA = Class IV) or LVEF≤40%

3. COPD > Stage 3 (FEV1<50%, FEV1/FVC<70%);

4. Cirrhosis (Child-Pugh Class C score);

5. Serum Albumin level < 3 g/dl

6. Any other severe concurrent disease which in the judgment of the investigator would
make the subject inappropriate for entry into this study

7. History of human immunodeficiency virus (HIV) infection

8. History of chronic active hepatitis including subjects who are carriers of hepatitis B
virus (HBV) or hepatitis C virus (HCV).

9. Presence of uncontrolled infection.

10. Evidence of active bleeding or bleeding diathesis

11. Brain metastases in symptomatic patients requiring ≥4 mg dexamethasone/day. However,
patients with treated brain metastases by surgery or radiation who are stable and
symptom-free (<4 mg dexamethasone/day) for a minimum period of 4 weeks post-treatment
are eligible.

12. Pregnant or lactating

13. Treatment with other investigational drugs within 14 days of start of the study drug
for non-myelosuppressive agents, and within 28 days of start of the study drug for
myelosuppressive agents.

14. Additional criteria for the Combination cohorts: Uncontrolled ascites (defined as 2 or
more palliative taps in the last 30 days before screening).

15. Additional criteria for the Combination cohorts with bevacizumab only: uncontrolled
clinically significant cardiac disease, hypertension, arrhythmias, or angina pectoris;
acute myocardial infarction or cerebrovascular accident within 12 months of initiation
of PROMITIL treatment.

16. Additional criteria for the Combination cohorts with bevacizumab only: Any
contraindication for treatment with Bevacizumab (e.g active bleeding, recent extensive
surgery).