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Trial to Determine Optimal Phase II Dose of the Oral Dual CAIX Inhibitor/ Radiosensitizer

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ClinicalTrials.gov Identifier: NCT02216669
Recruitment Status : Withdrawn (No financial agreement)
First Posted : August 15, 2014
Last Update Posted : March 3, 2017
Sponsor:
Information provided by (Responsible Party):
Maastricht Radiation Oncology

Brief Summary:

This is a Phase I multicenter, open-label, dose-escalation study of DTP348. DTP 348 is an oral dual drug with two mechanisms of action:

  1. carbonic anhydrase IX inhibitor which acidifies the intracellular pH through the sulfamide components
  2. radio sensitizer of hypoxic cells through its 5-nitroimidazole moiety

The study will be conducted in 2 parts. The phase I trials will be on the standard 3+3 design first as single agent then combined with radiotherapy:

  1. A single agent dose-escalation phase in patients with solid tumours.
  2. A dose-escalation phase in patients with HNSCC in combination with radiotherapy

The main objective is to determine the recommended phase II dose of DTP348 in combination with radiotherapy


Condition or disease Intervention/treatment Phase
Solid Tumors Head and Neck Neoplasms Drug: DTP348 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial to Determine Optimal Phase II Dose of the Oral Dual CAIX Inhibitor/ Radiosensitizer
Estimated Study Start Date : March 2017
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : July 2017

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Arm Intervention/treatment
Experimental: DTP348
Patients will receive a continuous oral dose of DTP348 for 7 days per week for 7 weeks
Drug: DTP348
Patients will receive a continuous oral dose of DTP348 for 7 days per week for 7 weeks
Other Name: 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylsulfamide




Primary Outcome Measures :
  1. The maximum-tolerated dose (MTD) of DTP348 as single agent [ Time Frame: 3 months ]
    To assess the safety and tolerability of DTP348 when administered orally as single agent in patients with advanced solid tumours in order to determine the Maximum Tolerated Dose (MTD) in relation with the occurrence of a Dose Limiting Toxicity (DLT).

  2. The maximum-tolerated dose (MTD) regimen of DTP348 as single agent in combination with radiotherapy [ Time Frame: 3 months ]
    To assess the safety and tolerability of DTP348 when administered orally in combination with radiotherapy in patients with HNSCC and to determine the Recommended Phase II Dose (RP2D) of this treatment combination.


Secondary Outcome Measures :
  1. Plasma concentration of DTP348 [ Time Frame: 3 months ]
    To characterise the Pharmacokinetic (PK) properties of DTP348 after oral administration as single agent

  2. Response rate according to RECIST, version 1.1, DTP348 monotherapy [ Time Frame: 3 months ]
    To evaluate the preliminary efficacy of DTP348 monotherapy in terms of anti-tumour activity

  3. Response rate according to RECIST version 1.1, DTP348 in combination of radiotherapy [ Time Frame: 3 months ]
    To evaluate the preliminary efficacy of DTP348 in combination with radiotherapy in terms of anti-tumour activity in patients with HNSCC.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologically or cytologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective.
  • Age 18 year or older
  • Performance status, WHO = 0 - 2
  • Subject must have adequate bone marrow, renal and hepatic function per local laboratory reference rage as follows:

Bone marrow: absolute neutrophil count (ANC) >/= 1,500/ul; platelets >/= 100,000/mm3 (independent of platelet transfusion, within 3 months prior to starting study drug); haemoglobin >/= 9.0 g/dL

Renal function: serum creatinine </= 2.0 mg/dL or calculated creatinine clearance >/= 50 mL/min

Hepatic function and enzymes: AST and ALT </= 2.5 x the upper limit of normal (ULN) of institution's normal range. Bilirubin </=1.5 x INL.

Subjects with liver metastases may have an AST and ALT of </= 5.0 x ULN

  • Measurable disease (RECIST, version 1.1)
  • Subjects with known brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and or radiation therapy followed by 21 days of stable neurologic function and no evidence of CNS disease progression as determined by comparing a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan performed during screening to a prior scan performed at least 4 weeks earlier and provided that the subject is asymptomatic, has no evidence of cavitation or haemorrhage and is on a stable dose of dexamethasone.
  • Females must have negative results for pregnancy tests performed:

At screening on a serum sample obtained within 7 days prior to initial study drug administration, and Prior to dosing on a urine pregnancy test will be obtained prior to study drug administration (cycle 1, day 1).

  • No breast feeding.
  • If female, subject must be either postmenopausal for at least 2 years, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or practicing at least one of the following methods of birth control:

Total abstinence from sexual intercourse as the preferred life style of the subject, periodic abstinence is not acceptable; Vasectomized partner; Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration (if the subject is currently using a hormonal contraceptive, she should also use a barrier method during the study and for 1 months after study completion); Intrauterine device (IUD); Double barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or creams);

- If male, subject must be surgically sterile or practicing at least 1 of the following methods of contraception and refrain from sperm donation, from initial drug administration until 90 days after the last dose of study drug: Partner(s) using an IUD; Partner(s) using hormonal contraceptives (oral, vaginal, parenteral or transdermal); Subject and/or partner(s) using double-barrier method (condoms, contraceptive sponge, diaphragm, or vaginal ring with spermicidal jellies or creams).

Total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not acceptable.

  • Ability to swallow and take oral medication. Patients that are dependent on a feeding tube can only be included in the study when entered in the last cohort, in which the PK of crushed study medication is the object of study.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Willing and able to undergo blood sampling for pharmacokinetics
  • Must voluntarily sign and date each informed consent, approved by an independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

  • If the subject has clinically significant and uncontrolled major medical condition(s) including but not limited to:

Uncontrolled seizure disorder, including focal or generalised seizure within the last 12 months; Uncontrolled nausea/vomiting/diarrhea; Active uncontrolled infection, including HIV and hepatitis (HBV, HCV) Symptomatic congestive heart failure, irreversible cardiac arrhythmias, acute or subacute coronary syndromes within the last year.

Psychiatric illness/social situation that would limit compliance with study requirements Any medical condition, with the opinion of the study investigator, places the subject at an unacceptably high risk for toxicities.

  • Female subject is pregnant or breastfeeding.
  • Subject has received any of the following anti-cancer therapies 21 days prior to the first dose of study drug:

Chemotherapy, immunotherapy, radiotherapy.

Any investigational therapy, including targeted small molecule agents. With the following exceptions:

  • Hormonal anticancer therapy must be stopped 7 days before starting day 1 of cycle 1 (C1D1)
  • Hormones for hypothyroidism, estrogen replacement therapy (ERT) or agonists required or suppress serum testosterone or estrogen levels (e.g. LHRH, GnRH, etc) for subjects with prostate, breast and ovarian cancer if on a stable dose for 21 days prior to the first dose of study drug.
  • Subject has received a biological agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.
  • Subject who requires parenteral nutrition, tube feeding or has evidence of partial bowel obstruction or perforation within 28 days prior to study drug administration.
  • The subject has had another active malignancy within the past 3 years except for any cancer in situ that the Principal Investigator considers to be cured.
  • In the opinion of the investigator, the subject is an unsuitable candidate to receive DTP348.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02216669


Locations
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Netherlands
Maastro Clinic
Maastricht, Limburg, Netherlands, 6229 ET
Sponsors and Collaborators
Maastricht Radiation Oncology
Investigators
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Principal Investigator: Frank Hoebers, Dr. Maastro Clinic, The Netherlands
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Responsible Party: Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT02216669    
Other Study ID Numbers: 08-2014
First Posted: August 15, 2014    Key Record Dates
Last Update Posted: March 3, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Maastricht Radiation Oncology:
Solid tumors
Head and Neck Neoplasms
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Imidazole
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action