We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
ClinicalTrials.gov Menu

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03435952
Recruitment Status : Recruiting
First Posted : February 19, 2018
Last Update Posted : February 27, 2023
BioMed Valley Discoveries, Inc
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

Some tumors are difficult to treat with chemotherapy or radiation. One of the reasons is that areas of the tumor do not have many blood vessels, which makes it difficult for drugs to reach those areas. One way that researchers have recently tried to overcome this problem is by injecting special kinds of bacteria into the tumors. These bacteria have been genetically changed to remove the chemicals that are poisonous to humans, but are still able to cause tumor cells to break down and die. The idea is that these bacteria may be able to assist chemotherapy drugs in fighting cancer.

The goal of this clinical research study is to find the highest tolerable dose of one of these bacterial therapies (Clostridium novyi-NT spores) that can be given in combination with pembrolizumab to patients with advanced solid tumors. The safety of this drug will also be studied, as well as whether it can help to control the disease.

This is an investigational study. Clostridium novyi-NT is not FDA approved or commercially available. It is currently being used for research purposes only. Pembrolizumab is FDA approved for the treatment of melanoma and different types of head and neck and non-small cell lung cancers. It is investigational to use these drugs in combination with each other in various types of advanced cancers.

The study doctor can describe how the study drugs are designed to work.

Up to 18 participants will be enrolled in this study. All will take part at MD Anderson.

Condition or disease Intervention/treatment Phase
Malignant Neoplasm of Breast Malignant Neoplasms of Digestive Organs Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System Malignant Neoplasms of Female Genital Organs Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites Malignant Neoplasms of Independent (Primary) Multiple Sites Malignant Neoplasms of Lip Oral Cavity and Pharynx Malignant Neoplasms of Male Genital Organs Malignant Neoplasms of Mesothelial and Soft Tissue Malignant Neoplasms of Respiratory and Intrathoracic Organs Malignant Neoplasms of Thyroid and Other Endocrine Glands Malignant Neoplasms of Urinary Tract Drug: Pembrolizumab Biological: Clostridium Novyi-NT Drug: Doxycycline Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Investigation of Pembrolizumab in Combination With Intratumoral Injection of Clostridium Novyi-NT in Patients With Treatment-Refractory Solid Tumors
Actual Study Start Date : July 10, 2018
Estimated Primary Completion Date : October 1, 2024
Estimated Study Completion Date : October 1, 2024

Arm Intervention/treatment
Experimental: Pembrolizumab + Clostridium novyi-NT

Participants receive Pembrolizumab by vein over about 30 minutes on Day 0 and then every 3 weeks for up to 12 months.

Clostridium novyi-NT injected into the tumor on Day 8.

Starting on Day 15, participant takes Doxycycline by mouth 2 times a day for the rest of participant's life to lower the risk of further growth of Clostridium novyi-NT

Drug: Pembrolizumab
200 mg by intravenous infusion starting on Day 0, and continuing every 3 weeks for up to 12 months.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475

Biological: Clostridium Novyi-NT

Participants given a single dose of Clostridium Novyi-NT by intratumoral injection on Day 8.

Clostridium Novyi-NT administered starting with Cohort 1 at a dose of 3 x 10^4 spores followed by dose escalation.

Drug: Doxycycline
Starting on Day 15, participant takes Doxycycline by mouth 2 times a day for the rest of participant's life to lower the risk of further growth of Clostridium novyi-NT
Other Names:
  • Vibramycin
  • Periostat
  • Doryx

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Intratumoral Injection of Clostridium Novyi-NT with Pembrolizumab [ Time Frame: 6 weeks ]
    MTD defined as the highest dose studied in which the incidence of DLT was less than 33%.

Secondary Outcome Measures :
  1. Preliminary Anti-Tumor Activity of Pembrolizumab in Combination with C. novyi-NT in the Injected Tumor and an Overall Response by RECIST 1.1 [ Time Frame: 6 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  1. Diagnosis of an advanced solid tumor malignancy. There must be a target tumor which is measureable, palpable or clearly identifiable under ultrasound or radiographic guidance and amenable to percutaneous injection of C. novyi-NT spores. The targeted lesion must have a longest diameter >/= 1 cm and < 12 cm and be measurable as defined by RECIST 1.1 criteria. The target lesion must not be located in either the thoracic, abdominal or pelvic cavities or in the brain. There must be no clinical, no functional, and no radiographic evidence of bone involvement at the site of the target lesion.
  2. History of prior treatment with at least one line of systemic anticancer therapy, when an approved systemic therapy is available, and no curative option is available for continued treatment.
  3. At least 4 weeks have elapsed since the completion of major surgery, and the patient has fully recovered from this surgery and any post-surgical complications.
  4. Patient must have adequate organ function as indicated by the following laboratory values. Hematological: Absolute neutrophil count (ANC) >/=1,500/mcL; Platelets >/=100,000/mcL; Hemoglobin >/=9g/dL or >/= 5.6 mmol/L. Renal: Serum creatinine </= 1.5 X upper limit of normal (ULN. Hepatic: serum total bilirubin </= 1.5 X ULN OR Direct bilirubin </= ULN for patients with total bilirubin levels > 1.5 ULN; AST (SGOT) and ALT (SPGT) </= 2.5 X ULN OR </= 5 X ULN for patients with liver metastases. Coagulation: International Normalized ration (INR) or Prothrombin Time (PT) </= 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT of PTT is within therapeutic range of intended use of anticoagulants; Activated partial Thromboplastin Time (aPTT) </= 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT of PTT is within therapeutic range of intended use of anticoagulants.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Patient is at least 18 years of age.
  7. Patient is capable of giving informed consent.
  8. Female patient of childbearing potential has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.
  9. Patient of childbearing potential is using either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from heterosexual activity throughout the study, starting with Visit 1 through 120 days after the last dose of study therapy. Approved contraceptive methods include 2 of the following barrier methods or one barrier method combined with a hormonal contraceptive: a. Intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides or condoms alone are not an acceptable method of contraception. b. Male patients must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study therapy.
  10. Patient has no significant valvular heart disease (trace or mild valvular stenosis or regurgitation is allowed).
  11. Patient is able to stay within 45 minutes driving time of an emergency room for 28 days after dosing with C. novyi-NT.
  12. The patient has a caregiver for 28 days after dosing with C. novyi-NT.
  13. Patient has a tumor sample from C. novyi-NT planned injected tumor lesion (newly obtained biopsy) for PD-L1 and immunologic response assessments. Patients must submit the tumor sample during screening at a central pathology laboratory.

Exclusion Criteria:

  1. Patient who has had chemotherapy, radiation therapy, or biological cancer therapy within four weeks prior to the first dose of study drug, or who has not recovered to CTCAE Grade 1 or better from the AEs due to cancer therapeutics administered more than four weeks earlier.
  2. Patient is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug. (A patient in the survival Follow up phase of an investigational agent where no further treatment is expected is eligible).
  3. Patient is on any systemic corticosteroid therapy within one week before the planned date for first dose of treatment or on any other form of immunosuppressive medication.
  4. Documented primary brain malignancy or brain metastases.
  5. Patient previously had a severe hypersensitivity reaction to treatment with another mAb.
  6. Patient has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement will not be excluded from the study.
  7. Patient has an active infection requiring systemic therapy.
  8. Patient has known history of Human Immunodeficiency Virus (HIV) (HIV ½ antibodies).
  9. Patient has a known history of or is positive for Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA [qualitative] is detected).
  10. Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
  11. Patient has received a live vaccine within 30 days prior to first dose.
  12. Patient has a foreign body which in the opinion of the treating investigator could be difficult to manage in case of infection.
  13. Clinically significant pleural effusion.
  14. Clinically significant pericardial effusion, circumferential pericardial effusion, or any effusion greater than 1.0 cm at any location around the heart.
  15. Need for ongoing treatment with an immunosuppressive agent.
  16. History of solid organ transplantation (with the exception of a corneal transplant > 3 months prior to screening).
  17. History of an ischemic insult in the previous 12 months (myocardial infarction, cerebral vascular accident, ischemic tissue from injury, transient ischemic attack).
  18. History of a significant medical illness deemed by the PI as unsuitable for the trial. For example: i. Symptomatic congestive heart failure ii. Psychiatric Illness/social situation that may make study dangerous iii. Unstable angina pectoris.
  19. History of asplenia.
  20. Antibiotic allergies that would preclude treatment for a C. novyi-NT infection.
  21. Treatment with antibiotics within 2 weeks (14 days) of dosing.
  22. Oxygen saturation (Sp02) of less than 95% on room air.
  23. Mean arterial blood pressure (BP) of less than 70 mmHg.
  24. Glasgow Coma Score of less than 15.
  25. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

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): NCT03435952

Layout table for location contacts
Contact: Rabia Khan 713-563-4667 RKhan@mdanderson.org

Layout table for location information
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sarina A Piha-Paul       spihapau@mdanderson.org   
Principal Investigator: Sarina A Piha-Paul         
Sponsors and Collaborators
M.D. Anderson Cancer Center
BioMed Valley Discoveries, Inc
Merck Sharp & Dohme LLC
Layout table for investigator information
Principal Investigator: Sarina Piha-Paul, MD, PHD M.D. Anderson Cancer Center
Principal Investigator: Sarina Piha-Paul, MD M.D. Anderson Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03435952    
Other Study ID Numbers: 2017-0719
NCI-2018-00757 ( Registry Identifier: NCI CTRP )
First Posted: February 19, 2018    Key Record Dates
Last Update Posted: February 27, 2023
Last Verified: February 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Clostridium Novyi-NT
C. novyi-NT
Solid tumor malignancies
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Genital Neoplasms, Female
Genital Neoplasms, Male
Urologic Neoplasms
Lip Neoplasms
Thyroid Neoplasms
Eye Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Urogenital Neoplasms
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Diseases
Genital Diseases, Male
Male Urogenital Diseases
Urologic Diseases
Mouth Neoplasms
Head and Neck Neoplasms
Lip Diseases
Mouth Diseases
Stomatognathic Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Thyroid Diseases
Eye Diseases