Phase I/II, Study of PM14 in Combination with Irinotecan in Pretreated Patients with Selected Advanced Solid Tumors

Phase 1

• Conditions: Advanced Solid Tumors; MedDRA version: 20.0Level: LLTClassification code 10007050Term: CancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-000415-23-ES
• Lead Sponsor: Pharma Mar, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-01
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1) Voluntarily signed and dated written informed consent prior to any specific study procedure.
2) Age = 18 years.
3) Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 1.
4) Histologically or cytologically-confirmed selected advanced solid tumors (see below) for which the standard of care therapies have failed, or are intolerant to standard of care therapies that are known to provide clinical benefit.
a) Gastrointestinal: esophageal carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, biliary tract
carcinoma, hepatocarcinoma and poorly differentiated (grade 3) gastroenteropancreatic neuroendocrine neoplasms (Ki 67
index >20%; mitotic count >20%).
b) Lung: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
c) Sarcoma: liposarcoma, leiomyosarcoma, synovial sarcoma and Ewing’s sarcoma.
d) Gynecological: epithelial ovarian carcinoma (including primary peritoneal disease and/or fallopian tube carcinomas
and/or endometrial adenocarcinomas), endometrial carcinoma and carcinoma of cervix.
e) Breast: ductal or lobular carcinoma.
f) Genitourinary tract tumors: urothelial bladder carcinoma, clear cell renal carcinoma and prostate adenocarcinoma.
g) Other: malignant pleural mesothelioma, extrapulmonary small cell carcinoma, and adrenocortical carcinoma.
5) In the Expansion stage only (tumor-specific cohort[s] at the RD):
a) Measurable disease according to RECIST v.1.1.
b) Documented disease progression per RECIST v.1.1 during or immediately after last therapy according to any of the
aforementioned criteria.
6) Washout periods:
a) At least three weeks since the last chemotherapy, radiotherapy (RT) >30 Gy, or monoclonal antibody (MAb)-containing
therapy.
b) At least two weeks since the last biological/investigational single-agent therapy (excluding MAbs) and/or palliative RT
(=10 fractions or =30 Gy total dose).
c) In patients with hormone-sensitive breast cancer progressing while on hormone therapy (except for luteinizing hormonereleasing hormone [LHRH] analogues in pre-menopausalwomen or megestrol acetate), all other hormonal therapies must be stopped at least one week before study treatment start.
d) Castrate-resistant prostate cancer (CRPC) patients may continue receiving hormone therapy prior to and during study
treatment.
Note: washout periods will be referred to the day of first cycle administration (Day 1), not to the day of registration.
7) Adequate bone marrow, renal, hepatic, and metabolic function (assessed = 7 days before registration):
a) Platelet count = 100 x 109/L, hemoglobin = 9.0 g/dL and absolute neutrophil count (ANC) = 2.0 x 109/L.
b) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3.0 x the upper limit of normal
(ULN), even in the presence of liver metastases.
c) Alkaline phosphatase (AP) = 2.5 x ULN (= 5 x ULN if diseaserelated/
in the case of liver metastases).
d) Total bilirubin = 1.5 x ULN or direct bilirubin = ULN.
e) Calculated creatinine clearance (CrCL) = 30 mL/minute (using
Cockcroft-Gault formula).
f) Creatine phosphokinase (CPK) = 2.5 x ULN.
g) Serum albumin = 3.0 g/dL.*
8) Recovery to grade = 1 or to baseline from any adverse event (AE)
derived from previous treatment (excluding alopecia and/or
cutaneous toxicity and/or peripheral neuropathy and/or fatigue
grade = 2).
* Albumin transfusion to increase the blood level in order to fulfill the
inclusion criterion is strictly forbidden.
Are the trial subjects under 18? no
Number of subjects for this ag

Exclusion Criteria

1) Concomitant diseases/conditions:
a) History or presence of unstable angina, myocardial infarction,
congestive heart failure, or clinically significant valvular heart
disease within the previous year.
b) Symptomatic arrhythmia or any uncontrolled arrhythmia
requiring ongoing treatment.
c) Myopathy or any clinical situation that causes significant and
persistent elevation of CPK (> 2.5 x ULN in two different
determinations performed one week apart).
d) Ongoing chronic alcohol consumption or cirrhosis with Child-
Pugh score B or C. Known Gilbert disease.
e) Active uncontrolled infection.
f) Known human immunodeficiency virus (HIV) or known
hepatitis C virus (HCV) infection or active hepatitis B. For
hepatitis B, this includes positive tests for both Hepatitis B
surface antigen (HBsAg) and quantitative Hepatitis B
polymerase chain reaction (PCR). For hepatitis C, this includes
positive tests for both Hepatitis C antibody and quantitative
Hepatitis C PCR.
g) Any past or present chronic inflammatory colon and/or liverdisease, past intestinal obstruction, pseudo or sub-occlusion or
paralysis.
h) Evident symptomatic pulmonary fibrosis or interstitial
pneumonitis, pleural or cardiac effusion rapidly increasing
and/or necessitating prompt local treatment within seven days.
i) Any other major illness that, in the Investigator’s judgment,
will substantially increase the risk associated with the
patient’s participation in this study (e.g., COVID-19).
2) Prior treatment with lurbinectedin (Zepzelca®), trabectedin
(Yondelis®) or topoisomerase I inhibitors is excluded, if the last
dose was administered within six months prior to the first infusion
of PM14 and irinotecan.
3) Use of (strong or moderate) inhibitors or strong inducers of
CYP3A4 activity within two weeks prior to the first infusion of
PM14 and irinotecan.
4) Active or untreated central nervous system (CNS) involvement.
Exception: patients with previously treated CNS metastases are
eligible provided they have to show radiographic stability
(defined as no CNS progression for at least four weeks from postradiotherapy
brain scan to brain scan performed during study
screening), and patients should not have neurologic
sign/symptoms secondary to the brain metastases or RT. Any
steroid treatment must be completed =14 days before the first
dose of study treatment. Note: for all SCLC patients regardless of
prior history of brain metastases or patients with other solid
tumors and previously treated CNS metastases, adequate CNS
imaging (contrast enhanced-computed tomography [CT] or
magnetic resonance imaging [MRI], if applicable) will be
performed at baseline to document any disease involvement.
5) Limitation of the patient’s ability to comply with the treatment or
follow-up protocol.
6) Women who are pregnant or breast feeding and fertile patients
(men and women) who are not using an effective method of
contraception.
Women of childbearing potential (WOCBP) must agree to use an effective contraception method to avoid pregnancy during the course of the trial (and for at least six months after the last infusion). Fertile male patients must agree to refrain from
fathering a child or donating sperm during the trial and for four months after the last infusion.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified