A Study Evaluating the Safety and Efficacy of PRV111, PRV211, and PRV131 in Subjects With Oral and Lung Cancers

Summary

Arm 1 ( Phase 2/3 Run in ): PRV111: Topical Locoregional Delivery Placed Over the Tumor Region Primary Endpoint: Overall Response Rate (ORR) Primary Objective: Demonstrate the safety and efficacy of PRV111 in patients with Carcinoma in Situ (CIS) (WHO 2017) Arm 2 (Phase 1) PRV211: Intraoperative Locoregional Delivery Placed into the Resected Tumor Bed Primary Endpoint: Safety Primary Objective: Determine Safety of PRV211 in intraoperative setting Arm 3 (Phase 1/2) PRV131: Intratumoral Injectable delivery into the Tumor Primary Endpoint: Safety and Objective Response Rate (ORR) Primary objective: Determine a safe and effective dose for PRV131 intratumoral injectable Subject Assignment: Subjects will be assigned to Arm 1, Arm 2, or Arm 3 of this study based on disease staging Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip or oral cavity Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx, M0 of the lip or oral cavity Arm 3a: Histologically confirmed squamous cell carcinoma (SCC) of the oral cavity, classified as clinical stage T1-T3, N0-1, M0 Arm 3b: Histologically confirmed malignant tumor in the lungs (primary or secondary), classified as clinical stage T1-2, N0, M0

Eligibility

Different diagnosis for ARM 1 \& ARM 2, however the rest of inclusion criteria are the same for both arms:

In order to be eligible to participate in the study, an individual must meet all of the following criteria:

• Diagnosis Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip or oral cavity Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx,M0 of the lip or oral cavity

Criteria for Inclusion for both ARM 1 \& ARM 2:

1. Tumors for which the cytological and architectural changes upon histopathological assessment warrant surgical intervention
2. Adult subjects, men and women, defined by age ≥18 years at the time of screening.
3. Tumor must be accessible, with no evidence of infection or active bleeding.
4. Tumor is amenable to surgical resection within 8 weeks of screening visit (Visit 0).
5. Clinically and/or radiologically measurable tumor.
6. Eastern Collaborative Oncology Group Performance Status of ≤2.
7. Male and female subjects of childbearing potential must agree to use 2 methods of effective contraception from screening and for at least 30 days after the final dose of investigational product. Appropriate birth control is defined as barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices, or naturally or surgically sterile (with documentation in the subject's medical records). Postmenopausal women are defined as presenting at least 12 months' natural spontaneous amenorrhea, or at least 6 weeks following surgical menopause (bilateral oophorectomy). Females of childbearing potential must be non-lactating and have a negative serum hCG within 14 days of treatment initiation.
8. Absence of any serious underlying medical conditions which could impair the ability of the subject to participate in the study.
9. Have a life expectancy of ≥3 months.
10. Willing and able to provide written informed consent.
11. Able to return to study site for treatment and follow-up visits as defined in the Protocol.

Criteria for Exclusion for both ARM 1 and ARM 2 (unless specified):

An individual who meets any of the following criteria will be excluded from participation in the study:

1. Subjects that are not eligible for surgery as SOC.
2. Patients with a prior history of invasive squamous cell carcinoma (Arm 1 only)
3. Tumors involving the marginal gingiva (Arm 1 only)
4. Squamous cell carcinoma (SCC) of the oral cavity that received previous radiotherapy.(Arm 1 only)
5. Systemic chemotherapy for the treatment of SCC of the head and neck less than 2 years prior to Screening (Arm 1 only)
6. Concurrent documented malignancy, with the exception of localized SCCs and basal cell carcinoma of the skin Exposure to any investigational agent within 3 months prior to Screening
7. Known allergy or hypersensitivity to platinum-containing agents, or known intolerance to a prior platinum- containing agent, or to any of the excipients, which, in the judgement of the physician will preclude re- exposure to platinum-containing agent
8. Active, uncontrolled infection requiring systemic therapy, such as but not limited to HIV, Syphilis, Hepatitis B, or Hepatitis C
9. Uncontrolled intercurrent illness that would risk subject safety, interfere with the objectives of the Protocol, or limit subject compliance with study requirements, as determined by the Investigator
10. Known or suspected pregnancy, planned pregnancy, or lactation
11. Any medical or psychiatric condition that may compromise the ability to give written informed consent
12. Known diagnosis of oral submucous fibrosis (Arm 1 only)
13. Known diagnosis of trismus (Arm 1 only)

Arm 3a:

Inclusion Criteria

Participants must meet all the following criteria to be eligible for the study:

1. Age: 18 years or older at the time of screening.
2. Diagnosis: Histologically confirmed squamous cell carcinoma (SCC) of the oral cavity, classified as clinical stage T1-T3, N0-N1, M0. This includes SCC of the lip with a significant mucosal component.
3. Tumor Accessibility: Tumor must be accessible for intratumoral injection, with no evidence of active infection.
4. Measurable Disease: Presence of clinically and/or radiologically measurable tumor.
5. Performance Status: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
6. Life Expectancy: Estimated life expectancy of at least 3 months.
7. Informed Consent: Ability and willingness to provide written informed consent.
8. Compliance: Ability to return to the study site for treatment visits as defined in the protocol.
9. Contraception: For participants of childbearing potential, agreement to use two effective methods of contraception during the study period.

Exclusion Criteria

Participants meeting any of the following criteria will be excluded from the study:

1. Surgical Eligibility: Not eligible for standard-of-care (SOC) surgery.
2. Renal and Hepatic Function: Abnormal renal and hepatic functions as determined by the investigator.
3. Cardiac Function: Corrected QT interval (QTc) \> 470 ms for women and \> 450 ms for men.
4. Bone Involvement: Known bone involvement by the tumor (Stage T4).
5. Other Cancers: Diagnosis of salivary gland cancer.
6. Prior Treatments: History of oral cancers that were nonresponsive to radiation or platinum-based chemotherapy within the past 12 months.
7. Multifocal Disease: Presence of multifocal invasive oral squamous cell carcinoma (OSCC).
8. Investigational Agents: Exposure to any investigational agent within 3 months prior to screening.
9. Allergies: Known allergy or hypersensitivity to platinum-containing agents or any excipients in the study drug, or known intolerance to prior platinum-based therapy that would preclude re-exposure.
10. Infections: Active, uncontrolled infections requiring systemic therapy, including but not limited to HIV, syphilis, hepatitis B, or hepatitis C.
11. Comorbid Conditions: Uncontrolled intercurrent illness that would pose a risk to subject safety, interfere with study objectives, or limit compliance, as determined by the investigator.
12. Pregnancy and Lactation: Known or suspected pregnancy, planned pregnancy, or current lactation.
13. Consent Capacity: Any medical or psychiatric condition that may compromise the ability to provide written informed consent.

3b: Inclusion Criteria

Participants must meet all the following criteria to be eligible for the study:

1. Age: 18 years or older at the time of screening.
2. Diagnosis: Histologically confirmed malignant tumor in the lungs (primary or secondary), classified as clinical stage T1-T2, N0, M0.
3. Tumor Accessibility: Tumor must be accessible for intratumoral injections via a bronchoscope, with no evidence of active infection.
4. Measurable Disease: Presence of clinically and/or radiologically measurable tumor.
5. Performance Status: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
6. Life Expectancy: Estimated life expectancy of at least 3 months.
7. Informed Consent: Ability and willingness to provide written informed consent.
8. Compliance: Ability to return to the study site for treatment visits as defined in the protocol.
9. Contraception: For participants of childbearing potential, agreement to use two effective methods of contraception during the study period.

Exclusion Criteria

Participants meeting any of the following criteria will be excluded from the study:

1. Surgical Eligibility: Not eligible for standard-of-care (SOC) surgery.
2. Renal and Hepatic Function: Abnormal renal and hepatic functions as determined by the investigator.
3. Cardiac Function: Corrected QT interval (QTc) \> 470 ms for women and \> 450 ms for men.
4. Bone Involvement: Known bone involvement by the tumor (Stage T4).
5. Other Cancers: Active concurrent malignancies that require systemic therapy.
6. Prior Treatments: History of cancers in the lung that were nonresponsive to radiation or platinum-based chemotherapy within the past 12 months.
7. Investigational Agents: Exposure to any investigational agent within 3 months prior to screening.
8. Allergies: Known allergy or hypersensitivity to platinum-containing agents or any excipients in the study drug or known intolerance to prior platinum-based therapy that would preclude re-exposure.
9. Infections: Active, uncontrolled infections requiring systemic therapy, including but not limited to HIV, syphilis, hepatitis B, or hepatitis C.
10. Comorbid Conditions: Uncontrolled intercurrent illness that would pose a risk to subject safety, interfere with study objectives, or limit compliance, as determined by the investigator.
11. Pregnancy and Lactation: Known or suspected pregnancy, planned pregnancy, or current lactation.
12. Consent Capacity: Any medical or psychiatric condition that may compromise the ability to provide written informed consent.

Conditions3

Interventions3

Locations4 sites

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