Talimogene Laherparepvec, Chemotherapy, and Radiation Therapy Before Surgery in Treating Patients With Locally Advanced or Metastatic Rectal Cancer

NCT03300544 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: NCI-2016-01844NCI1005810058UM1CA186688
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose and side effects of talimogene laherparepvec in combination with 5-fluorouracil, leucovorin, oxaliplatin, capecitabine, and chemoradiation before surgery in treating patients with rectal cancer that has spread from where it started to nearby tissue and lymph nodes. Drugs used in immunotherapy, such as talimogene laherparepvec, may stimulate the body's immune system to fight tumor cells. Drugs used in chemotherapy, such as 5-fluorouracil, leucovorin, oxaliplatin, and capecitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving talimogene laherparepvec, 5-fluorouracil, leucovorin, oxaliplatin, and capecitabine and chemoradiation before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Conditions

Locally Advanced Rectal Adenocarcinoma; Metastatic Rectal Adenocarcinoma; Rectal Adenocarcinoma; Stage III Rectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Determination of Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD) of Talimogene Laherparepvec in Combination With Chemotherapy and Radiation in Rectal Cancer.

  Assessed using the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 5.0.

  4 weeks after surgery

Secondary Outcomes (2)

• To Establish Safety and Feasibility of the Combination

  4 weeks after surgery

• Determine the Neoadjuvant Rectal (NAR) Score of Talimogene Laherparepvec With Chemotherapy and Radiation.

  4 weeks after surgery

Study Arms (1)

Treatment (T-VEC, capecitabine, chemoradiation)

EXPERIMENTAL

Patients receive talimogene laherparepvec intralesionally via endoscopy on weeks 1, 4, 6, and 8. Patients receive 5-fluorouracil IV by bolus and over 46 hours, leucovorin IV bolus, and oxaliplatin IV over 2 hours on weeks 2 and 4. Patients also receive capecitabine orally PO BID followed by radiation therapy for 28 fractions on days 1-5 of weeks 8-13. Patients undergo resection surgery on weeks 21-25.

Drug: Capecitabine; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Radiation: Radiation Therapy; Biological: Talimogene Laherparepvec

Interventions

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Treatment (T-VEC, capecitabine, chemoradiation)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (T-VEC, capecitabine, chemoradiation)

Leucovorin DRUG

Given IV

Also known as: Folinic acid

Treatment (T-VEC, capecitabine, chemoradiation)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (T-VEC, capecitabine, chemoradiation)

Radiation Therapy RADIATION

Undergo chemoradiation

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (T-VEC, capecitabine, chemoradiation)

Talimogene Laherparepvec BIOLOGICAL

Given intralesionally

Also known as: ICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene, Imlygic, JS1 34.5-hGMCSF 47- pA-, T-VEC

Treatment (T-VEC, capecitabine, chemoradiation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For dose escalation: Patients must have A) histologically or cytologically confirmed low lying (up to 6 cm of anal verge) rectal adenocarcinoma eligible for radiation therapy to rectal tumor, B) if the treatment is palliative in the metastatic setting, no additional requirements for tumor size or nodal involvement is needed; C) if the treatment is in the neoadjuvant setting, the tumor must ALSO be high-risk locally advanced rectal cancer defined as T3-4, N+, and/or at risk for a positive radial margin (as determined by the surgeon)
• For dose expansion: Patients must have A) histologically or cytologically confirmed rectal adenocarcinoma eligible for radiation therapy to rectal tumor irrespective of location from anal verge, B) if the treatment is palliative in the metastatic setting, no additional requirements for tumor size or nodal involvement is needed; C) if the treatment is in the neoadjuvant setting, the tumor must ALSO be high-risk locally advanced rectal cancer defined as T3-4, N+, and/or at risk for a positive radial margin (as determined by the surgeon)
• Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of talimogene laherparepvec in combination with chemotherapy in patients \< 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L
• Hemoglobin \>= 9 g/dL
• Platelets \>= 100,000 x 10\^9 /L
• Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert's syndrome, who can have total bilirubin \< 3 mg/DL)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional ULN
• Serum creatinine =\< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) \>= 50 mL/min OR 24-hour urine creatinine clearance \>= 50 mL/min
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 x institutional unless the subject is on anticoagulant therapy (if the subject is receiving anticoagulant therapy, PT, and activated partial thromboplastin time \[aPTT\] must be within therapeutic range of intended use of anticoagulants)
• Patients must have signed informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary; patients must be made aware of their other treatment options
• Talimogene laherparepvec, as well as other therapeutic agents used in this trial including radiation and capecitabine, may cause fetal harm when administered to a pregnant woman; women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; WOCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation, and for four months after the last dose of the drug; WOCBP must have a negative serum pregnancy test within 72 hours prior to enrollment and agree to use effective contraception throughout the treatment period and for 4 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have had radiotherapy within \< 4 weeks are ineligible
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) except alopecia are ineligible
• Use of other investigational, chemotherapeutic or targeted drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of talimogene laherparepvec and during the study are ineligible
• Patients who have previously been treated with talimogene laherparepvec, any other oncolytic virus or pelvic radiation are ineligible
• Patients with known active central nervous system (CNS) metastases are ineligible; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases
• Patients with a known immediate or delayed hypersensitivity reaction or idiosyncrasy to talimogene laherparepvec or any of its components, capecitabine, fluorouracil (5-FU) and / or oxaliplatin are ineligible
• Patients with a history or evidence of active autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other); or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) within 2 months of enrollment are ineligible; (replacement therapy \[e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency\] is not considered a form of systemic treatment for autoimmune disease)
• Patients with evidence of clinically significant immunosuppression such as the following are ineligible:
• Primary immunodeficiency state such as severe combined immunodeficiency disease
• Concurrent opportunistic infection
• Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 2 months prior to enrollment
• Patients with active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis) are ineligible
• Patients with viral infections requiring intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use are ineligible
• Patients with other viral infections are ineligible:
• Known to have acute or chronic active hepatitis B or hepatitis C infection

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Fluorouracil; dehydroftorafur; Leucovorin; Oxaliplatin; Radiotherapy; Radiation; talimogene laherparepvec

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Arvind Dasari
• Organization: M D Anderson Cancer Center

adasari@mdanderson.org

(713) 792-2828

Study Officials

• Nageshwara V Dasari

  University of Texas MD Anderson Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: October 3, 2017
• Study Start: May 14, 2019
• Primary Completion: March 22, 2022
• Study Completion: March 22, 2022
• Last Updated: May 23, 2024
• Results First Posted: May 1, 2024

Record last verified: 2024-01

Locations

US (1)