Informations générales (source: ClinicalTrials.gov)
Phase I, Open-label, Dose-escalating, Clinical and Pharmacokinetic Study of PM14 Administered Intravenously to Patients with Advanced Solid Tumors
Interventional
Phase 1
PharmaMar (Voir sur ClinicalTrials)
septembre 2017
août 2025
05 avril 2025
Despite recent advances in the treatment of solid tumors in general, advanced
(metastatic) disease remains mostly incurable and there is an urgent need to develop new
therapeutic options for these patients, particularly investigational drugs with novel
mechanisms of action. The investigation of new combination regimens of non-crossresistant
agents with acceptable-and not completely overlapping-toxicities has been a major way to
improve response rate and outcome of patients with advanced solid tumors.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Christophe Massard | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Voluntarily signed and dated written informed consent (IC), obtained prior to any
specific study procedure.
2. Age ≥18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1
4. For the Dose escalation phase:
Patients with pathologically confirmed diagnosis of advanced solid tumors for whom
no curative standard therapy exists.
For the Expansion phase:
Patients with pathologically confirmed diagnosis of one of the following
malignancies, for whom the standard of care therapies have failed, or are intolerant
to standard of care therapies that are known to provide clinical benefit:
1. Gastrointestinal tumors: colorectal cancer, gastric cancer.
2. Sarcomas: liposarcoma, leiomyosarcoma, synovial sarcoma, Ewing's sarcoma.
3. Tumors with deleterious germline BRCA mutation: epithelial ovarian cancer
(including primary peritoneal and fallopian tube cancer), breast cancer,
pancreatic cancer, prostate cancer, or any other malignancies.
4. Epithelial ovarian cancer (including primary peritoneal and fallopian tube
cancer) with no deleterious germline BRCA mutations or with unknown BRCA
status.
5. Adrenocortical carcinoma.
5. Patients included in the Expansion phase need to meet the following requirements
regarding the maximum number of prior chemotherapy regimens (no limit for biological
therapies):
1. Gastrointestinal tumors: no more than three prior chemotherapy lines for
colorectal cancer; and no more than two prior chemotherapy lines for gastric
cancer.
2. Sarcomas: no more than two prior chemotherapy lines for liposarcoma,
leiomyosarcoma and synovial sarcoma; and no more than three prior chemotherapy
lines for Ewing's sarcoma.
3. Tumors with deleterious germline BRCA mutation: no more than three prior
chemotherapy lines for breast cancer; and no more than two prior chemotherapy
lines for prostate cancer, ovarian cancer, pancreatic cancer, gastric
carcinoma, or any other malignancies.
4. Epithelial ovarian cancer with unknown BRCA status or no deleterious germline
BRCA mutations: no more than three prior chemotherapy lines.
5. Adrenocortical cancer: no more than one prior chemotherapy line (excluding
mitotane as single agent or associated with no chemotherapeutic agents).
Note: for the purpose of this criterion, the following situations will be considered
as one chemotherapy line:
- Adjuvant chemotherapy; neoadjuvant chemotherapy; both adjuvant and neoadjuvant
chemotherapy (except if time to relapse was >12 months, in which case it will
not be considered as one line); and
- Change of chemotherapy due to reasons other than PD, such as toxicity (in this
case, the two lines will count as a single line).
6. Life expectancy ≥3 months.
7. Patients with measurable or non-measurable disease according to the RECIST v.1.1 are
eligible during the dose escalation phase.
8. Patients included in the Expansion phase must have:
1. Measurable disease according to the RECIST v.1.1 and/or evaluable disease by
serum markers in case of prostate and ovarian cancer (according to the PSAWGR
and the GCIG specific criteria, respectively).
2. Confirmed progressive disease after last therapy at study entry.
9. Recovery to grade ≤1 from drug-related AEs of previous treatments, excluding
alopecia and grade 1/2 asthenia or fatigue, according to the NCI-CTCAE v.4.
10. Laboratory values within seven days prior to first infusion:
1. ANC ≥1.5 x 10^9/L, platelet count ≥100 x 10^9/L and hemoglobin ≥9 g/dL
(patients may be transfused for anemia as clinically indicated prior to study
entry).
2. AST and ALT ≤3.0 x ULN.
3. Total bilirubin ≤ULN (up to 1.5 x ULN for patients with Gilbert's syndrome).
4. Creatinine clearance ≥30 mL/min (calculated using the Cockcroft and Gault's
formula).
5. Serum albumin ≥3 g/dL.
11. Wash-out periods:
1. At least three weeks since the last chemotherapy (six weeks if therapy included
nitrosoureas or systemic mitomycin C).
2. At least four weeks since the last monoclonal antibody (MAb)-containing therapy
or curative radiotherapy (RT).
3. 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).
4. In patients with hormone-sensitive breast cancer progressing while on hormone
therapy (except for luteinizing hormone-releasing hormone (LHRH) analogues in
pre-menopausal women or megestrol acetate), all other hormonal therapies must
be stopped at least one week before study treatment start.
5. Castrate-resistant prostate cancer (CRPC) patients may continue receiving
hormone therapy prior to and during study treatment.
1. Voluntarily signed and dated written informed consent (IC), obtained prior to any
specific study procedure.
2. Age ≥18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1
4. For the Dose escalation phase:
Patients with pathologically confirmed diagnosis of advanced solid tumors for whom
no curative standard therapy exists.
For the Expansion phase:
Patients with pathologically confirmed diagnosis of one of the following
malignancies, for whom the standard of care therapies have failed, or are intolerant
to standard of care therapies that are known to provide clinical benefit:
1. Gastrointestinal tumors: colorectal cancer, gastric cancer.
2. Sarcomas: liposarcoma, leiomyosarcoma, synovial sarcoma, Ewing's sarcoma.
3. Tumors with deleterious germline BRCA mutation: epithelial ovarian cancer
(including primary peritoneal and fallopian tube cancer), breast cancer,
pancreatic cancer, prostate cancer, or any other malignancies.
4. Epithelial ovarian cancer (including primary peritoneal and fallopian tube
cancer) with no deleterious germline BRCA mutations or with unknown BRCA
status.
5. Adrenocortical carcinoma.
5. Patients included in the Expansion phase need to meet the following requirements
regarding the maximum number of prior chemotherapy regimens (no limit for biological
therapies):
1. Gastrointestinal tumors: no more than three prior chemotherapy lines for
colorectal cancer; and no more than two prior chemotherapy lines for gastric
cancer.
2. Sarcomas: no more than two prior chemotherapy lines for liposarcoma,
leiomyosarcoma and synovial sarcoma; and no more than three prior chemotherapy
lines for Ewing's sarcoma.
3. Tumors with deleterious germline BRCA mutation: no more than three prior
chemotherapy lines for breast cancer; and no more than two prior chemotherapy
lines for prostate cancer, ovarian cancer, pancreatic cancer, gastric
carcinoma, or any other malignancies.
4. Epithelial ovarian cancer with unknown BRCA status or no deleterious germline
BRCA mutations: no more than three prior chemotherapy lines.
5. Adrenocortical cancer: no more than one prior chemotherapy line (excluding
mitotane as single agent or associated with no chemotherapeutic agents).
Note: for the purpose of this criterion, the following situations will be considered
as one chemotherapy line:
- Adjuvant chemotherapy; neoadjuvant chemotherapy; both adjuvant and neoadjuvant
chemotherapy (except if time to relapse was >12 months, in which case it will
not be considered as one line); and
- Change of chemotherapy due to reasons other than PD, such as toxicity (in this
case, the two lines will count as a single line).
6. Life expectancy ≥3 months.
7. Patients with measurable or non-measurable disease according to the RECIST v.1.1 are
eligible during the dose escalation phase.
8. Patients included in the Expansion phase must have:
1. Measurable disease according to the RECIST v.1.1 and/or evaluable disease by
serum markers in case of prostate and ovarian cancer (according to the PSAWGR
and the GCIG specific criteria, respectively).
2. Confirmed progressive disease after last therapy at study entry.
9. Recovery to grade ≤1 from drug-related AEs of previous treatments, excluding
alopecia and grade 1/2 asthenia or fatigue, according to the NCI-CTCAE v.4.
10. Laboratory values within seven days prior to first infusion:
1. ANC ≥1.5 x 10^9/L, platelet count ≥100 x 10^9/L and hemoglobin ≥9 g/dL
(patients may be transfused for anemia as clinically indicated prior to study
entry).
2. AST and ALT ≤3.0 x ULN.
3. Total bilirubin ≤ULN (up to 1.5 x ULN for patients with Gilbert's syndrome).
4. Creatinine clearance ≥30 mL/min (calculated using the Cockcroft and Gault's
formula).
5. Serum albumin ≥3 g/dL.
11. Wash-out periods:
1. At least three weeks since the last chemotherapy (six weeks if therapy included
nitrosoureas or systemic mitomycin C).
2. At least four weeks since the last monoclonal antibody (MAb)-containing therapy
or curative radiotherapy (RT).
3. 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).
4. In patients with hormone-sensitive breast cancer progressing while on hormone
therapy (except for luteinizing hormone-releasing hormone (LHRH) analogues in
pre-menopausal women or megestrol acetate), all other hormonal therapies must
be stopped at least one week before study treatment start.
5. Castrate-resistant prostate cancer (CRPC) patients may continue receiving
hormone therapy prior to and during study treatment.
1. Concomitant diseases/conditions:
1. Increased cardiac risk:
- Uncontrolled arterial hypertension despite optimal management (≥160/100
mmHg).
- Presence of clinically relevant valvular disease.
- History of long QT syndrome.
- Corrected QT interval (QTcF, Fridericia correction) ≥450 msec on screening
electrocardiogram (ECG).
- History of ischemic heart disease, including myocardial infarction,
angina, coronary arteriography or cardiac stress testing with findings
consistent with coronary occlusion or infarction ≤6 months prior to study
entry.
- History of heart failure or left ventricular dysfunction (left ventricular
ejection fraction [LVEF] below normal values) by multiple-gated
acquisition scan (MUGA) or echocardiography (ECHO).
- ECG abnormalities, including any of the following: left bundle branch
block, right bundle branch block with left anterior hemiblock, second
(Mobitz II) or third degree atrioventricular block.
- Symptomatic arrhythmia (excluding anemia-related sinusal tachycardia grade
≤2) or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc
grade ≥2; or presence of unstable atrial fibrillation. Patients with
stable atrial fibrillation on treatment are allowed provided they do not
meet any other cardiac or prohibited drug exclusion criterion.
- Clinically significant resting bradycardia (<50 beats per minute).
- Concomitant medication with risk of inducing torsades de pointes, which
cannot be discontinued or switched to an alternative drug prior to start
PM14 dosing.
- Use of a cardiac pacemaker.
2. Active infection requiring systemic treatment.
3. Known human immunodeficiency virus (HIV) or known hepatitis C virus (HCV)
infection or active hepatitis B.
4. 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. Symptomatic, high dose steroid-requiring, and progressing central nervous system
(CNS) disease. Exceptions will be made for (i) patients who have completed
radiotherapy at least four weeks prior to inclusion (asymptomatic, non-progressing
patients taking steroids in the process of already being tapered within two weeks
prior to inclusion), and (ii) patients with asymptomatic brain metastasis without
need for radiotherapy or steroids.
3. Patients with carcinomatous meningitis regardless of clinical stability.
4. Prior bone marrow or stem cell transplantation, or radiation therapy in more than
35% of bone marrow.
5. Prior treatment with trabectedin or Lurbinectedin (PM01183) within six months prior
to onset of study treatment.
6. Use of (strong or moderate) inhibitors or strong inducers of CYP3A4 activity within
two weeks prior to the first infusion of PM14.
7. Known hypersensitivity to any of the components of the drug product
8. Limitation of the patient's ability to comply with the treatment or to follow the
protocol procedures.
9. Pregnant or lactating women. Women of childbearing potential (WOCBP) must agree to
use an effective contraception method to avoid pregnancy during trial treatment and
for at least six months after the last infusion. Fertile male patients must agree to
refrain from fathering a child or donating sperm and to use an effective
contraception method during treatment and for four months after the last infusion.
WOCBP who are partners of fertile male patients must use an effective contraception
method during the patients' treatment and for four months after the last infusion.